An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. It can serve as a salvage mechanism for returning adenosine to nucleic acids. EC 2.7.1.20.
A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.
An antibiotic purine ribonucleoside that readily substitutes for adenosine in the biological system, but its incorporation into DNA and RNA has an inhibitory effect on the metabolism of these nucleic acids.
A subclass of adenosine A2 receptors found in LEUKOCYTES, the SPLEEN, the THYMUS and a variety of other tissues. It is generally considered to be a receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.
An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.
A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of tissues including the BRAIN and DORSAL HORN NEURONS. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.
Drugs that inhibit ADENOSINE DEAMINASE activity.
A purine nucleoside that has hypoxanthine linked by the N9 nitrogen to the C1 carbon of ribose. It is an intermediate in the degradation of purines and purine nucleosides to uric acid and in pathways of purine salvage. It also occurs in the anticodon of certain transfer RNA molecules. (Dorland, 28th ed)
A subclass of adenosine A2 receptors found in the CECUM, the COLON, the BLADDER, and a variety of other tissues. It is generally considered to be a low affinity receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.
Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.
A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).
A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of locations including the BRAIN and endocrine tissues. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.
Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.
A glycoprotein enzyme present in various organs and in many cells. The enzyme catalyzes the hydrolysis of a 5'-ribonucleotide to a ribonucleoside and orthophosphate in the presence of water. It is cation-dependent and exists in a membrane-bound and soluble form. EC 3.1.3.5.
Pyrazolopyrimidine ribonucleosides isolated from Nocardia interforma. They are antineoplastic antibiotics with cytostatic properties.
Nucleosides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)
A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
A subclass of ADENOSINE RECEPTORS that are generally considered to be coupled to the GS, STIMULATORY G-PROTEIN which causes up regulation of CYCLIC AMP.
A potent inhibitor of ADENOSINE DEAMINASE. The drug induces APOPTOSIS of LYMPHOCYTES, and is used in the treatment of many lymphoproliferative malignancies, particularly HAIRY CELL LEUKEMIA. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.
Inosine 5'-Monophosphate. A purine nucleotide which has hypoxanthine as the base and one phosphate group esterified to the sugar moiety.
Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.
Adenosine molecules which can be substituted in any position, but are lacking one hydroxyl group in the ribose part of the molecule.
Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.
An aminopurine factor in plant extracts that induces cell division. (Grant & Hackh's Chemical Dict, 5th ed)
2-Chloroadenosine. A metabolically stable analog of adenosine which acts as an adenosine receptor agonist. The compound has a potent effect on the peripheral and central nervous system.
Purine bases found in body tissues and fluids and in some plants.
A ribonucleoside antibiotic synergist and adenosine deaminase inhibitor isolated from Nocardia interforma and Streptomyces kaniharaensis. It is proposed as an antineoplastic synergist and immunosuppressant.
A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-.
Sulfhydryl analog of INOSINE that inhibits nucleoside transport across erythrocyte plasma membranes, and has immunosuppressive properties. It has been used similarly to MERCAPTOPURINE in the treatment of leukemia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p503)
Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.
6-(Methylthio)-9-beta-D-ribofuranosylpurine. An analog of inosine with a methylthio group replacing the hydroxyl group in the 6-position.
Agents that inhibit PROTEIN KINASES.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway.
A broad class of substances encompassing all those that do not include carbon and its derivatives as their principal elements. However, carbides, carbonates, cyanides, cyanates, and carbon disulfide are included in this class.
An enzyme which catalyzes the catabolism of S-ADENOSYLHOMOCYSTEINE to ADENOSINE and HOMOCYSTEINE. It may play a role in regulating the concentration of intracellular adenosylhomocysteine.
Catalyze the hydrolysis of nucleosides with the elimination of ammonia.
Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
The rate dynamics in chemical or physical systems.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Purine bases related to hypoxanthine, an intermediate product of uric acid synthesis and a breakdown product of adenine catabolism.
Adenine nucleotides are molecules that consist of an adenine base attached to a ribose sugar and one, two, or three phosphate groups, including adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP), which play crucial roles in energy transfer and signaling processes within cells.
5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.
A purine base and a fundamental unit of ADENINE NUCLEOTIDES.
A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
A parasitic hemoflagellate of the subgenus Leishmania leishmania that infects man and animals and causes visceral leishmaniasis (LEISHMANIASIS, VISCERAL). The sandfly genera Phlebotomus and Lutzomyia are the vectors.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
4-Amino-5-cyano-7-(D-ribofuranosyl)-7H- pyrrolo(2,3-d)pyrimidine. Antibiotic antimetabolite isolated from Streptomyces toyocaensis cultures. It is an analog of adenosine, blocks RNA synthesis and ribosome function, and is used mainly as a tool in biochemistry.
The double-layered skin fold that covers the GLANS PENIS, the head of the penis.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
An enzyme that catalyzes reversibly the phosphorylation of deoxycytidine with the formation of a nucleoside diphosphate and deoxycytidine monophosphate. Cytosine arabinoside can also act as an acceptor. All natural nucleoside triphosphates, except deoxycytidine triphosphate, can act as donors. The enzyme is induced by some viruses, particularly the herpes simplex virus (HERPESVIRUS HOMINIS). EC 2.7.1.74.
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
An imidazole derivative which is a metabolite of the antineoplastic agents BIC and DIC. By itself, or as the ribonucleotide, it is used as a condensation agent in the preparation of nucleosides and nucleotides. Compounded with orotic acid, it is used to treat liver diseases.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Established cell cultures that have the potential to propagate indefinitely.
A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.
Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP.
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
Morpholines are organic compounds containing a morpholine ring, which is a saturated six-membered heterocycle made up of four carbon atoms and two oxygen atoms (OCC1CCO), often used as functional groups in pharmaceuticals, agrochemicals, and materials science due to their versatile chemical properties.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
Nucleotides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)

Quantification of extracellular and intracellular adenosine production: understanding the transmembranous concentration gradient. (1/217)

BACKGROUND: Inhibitors of adenosine membrane transport cause vasodilation and enhance the plasma adenosine concentration. However, it is unclear why the plasma adenosine concentration rises rather than falls when membrane transport is inhibited. We tested the hypothesis that the cytosolic adenosine concentration exceeds the interstitial concentration under well-oxygenated conditions. METHODS AND RESULTS: In isolated, isovolumically working guinea pig hearts (n=50), the release rate of adenosine and accumulation of S-adenosylhomocysteine (after 20 minutes of 200 micromol/L homocysteine), a measure of the free cytosolic adenosine concentration, were determined in the absence and presence of specific and powerful blockers of adenosine membrane transport (nitrobenzylthioinosine 1 micromol/L), adenosine deaminase (erythro-9-hydroxy-nonyl-adenine 5 micromol/L), and adenosine kinase (iodotubericidine 10 micromol/L). Data analysis with a distributed multicompartment model revealed a total cardiac adenosine production rate of 2294 pmol. min-1. g-1, of which 8% was produced in the extracellular region. Because of a high rate of intracellular metabolism, however, 70.3% of extracellularly produced adenosine was taken up into cellular regions, an effect that was effectively eliminated by membrane transport block. The resulting approximately 2.8-fold increase of the interstitial adenosine concentration evoked near-maximal coronary dilation. CONCLUSIONS: We rejected the hypothesis that the cytosolic adenosine concentration exceeds the interstitial. Rather, there is significant extracellular production, and the parenchymal cell represents a sink, not a source, for adenosine under well-oxygenated conditions.  (+info)

Molecular cloning and expression of adenosine kinase from Leishmania donovani: identification of unconventional P-loop motif. (2/217)

The unique catalytic characteristics of adenosine kinase (Adk) and its stage-specific differential activity pattern have made this enzyme a prospective target for chemotherapeutic manipulation in the purine-auxotrophic parasitic protozoan Leishmania donovani. However, nothing is known about the structure of the parasite Adk. We report here the cloning of its gene and the characterization of the gene product. The encoded protein, consisting of 345 amino acid residues with a calculated molecular mass of 37173 Da, shares limited but significant similarity with sugar kinases and inosine-guanosine kinase of microbial origin, supporting the notion that these enzymes might have the same ancestral origin. The identity of the parasite enzyme with the corresponding enzyme from two other sources so far described was only 40%. Furthermore, 5' RNA mapping studies indicated that the Adk gene transcript is matured post-transcriptionally with the trans-splicing of the mini-exon (spliced leader) occurring at nt -160 from the predicted translation initiation site. The biochemical properties of the recombinant enzyme were similar to those of the enzyme isolated from leishmanial cells. The intrinsic tryptophan fluorescence of the enzyme was substrate-sensitive. On the basis of a multiple protein-alignment sequence comparison and ATP-induced fluorescence quenching in the presence or the absence of KI and acrylamide, the docking site for ATP has been provisionally identified and shown to have marked divergence from the consensus P-loop motif reported for ATP- or GTP-binding proteins from other sources.  (+info)

Adenosine kinase inhibitors as a novel approach to anticonvulsant therapy. (3/217)

Adenosine levels increase at seizure foci as part of a postulated endogenous negative feedback mechanism that controls seizure activity through activation of A1 adenosine receptors. Agents that amplify this site- and event-specific surge of adenosine could provide antiseizure activity similar to that of adenosine receptor agonists but with fewer dose-limiting side effects. Inhibitors of adenosine kinase (AK) were examined because AK is normally the primary route of adenosine metabolism. The AK inhibitors 5'-amino-5'-deoxyadenosine, 5-iodotubercidin, and 5'-deoxy-5-iodotubercidin inhibited maximal electroshock (MES) seizures in rats. Several structural classes of novel AK inhibitors were identified and shown to exhibit similar activity, including a prototype inhibitor, 4-(N-phenylamino)-5-phenyl-7-(5'-deoxyribofuranosyl)pyrrolo[2, 3-d]pyrimidine (GP683; MES ED50 = 1.1 mg/kg). AK inhibitors also reduced epileptiform discharges induced by removal of Mg2+ in a rat neocortical preparation. Overall, inhibitors of adenosine deaminase or of adenosine transport were less effective. The antiseizure activities of GP683 in the in vivo and in vitro preparations were reversed by the adenosine receptor antagonists theophylline and 8-(p-sulfophenyl)theophylline. GP683 showed little or no hypotension or bradycardia and minimal hypothermic effect at anticonvulsant doses. This improved side effect profile contrasts markedly with the profound hypotension, bradycardia, and hypothermia and greater inhibition of motor function observed with the adenosine receptor agonist N6-cyclopentyladenosine and opens the way to clinical evaluation of AK inhibitors as a novel, adenosine-based approach to anticonvulsant therapy.  (+info)

Metabolism and selective toxicity of 6-nitrobenzylthioinosine in Toxoplasma gondii. (4/217)

The purine nucleoside analogue NBMPR (nitrobenzylthioinosine or 6-[(4-nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine) was selectively phosphorylated to its nucleoside 5'-monophosphate by Toxoplasma gondii but not mammalian adenosine kinase (EC 2.7.1.20). NBMPR was also cleaved in toxoplasma to its nucleobase, nitrobenzylmercaptopurine. However, nitrobenzylmercaptopurine was not a substrate for either adenosine kinase or hypoxanthine-guanine-xanthine phosphoribosyltransferase (EC 2.4.2.8). Because of this unique and previously unknown metabolism of NBMPR by the parasite, the effect of NBMPR as an antitoxoplasmic agent was tested. NBMPR killed T. gondii grown in human fibroblasts in a dose-dependent manner, with a 50% inhibitory concentration of approximately 10 microM and without apparent toxicity to host cells. Doses of up to 100 microM had no significant toxic effect on uninfected host cells. The promising antitoxoplasmic effect of NBMPR led to the testing of other 6-substituted 9-beta-D-ribofuranosylpurines, which were shown to be good ligands of the parasite adenosine kinase (M. H. Iltzsch, S. S. Uber, K. O. Tankersley, and M. H. el Kouni, Biochem. Pharmacol. 49:1501-1512, 1995), as antitoxoplasmic agents. Among the analogues tested, 6-benzylthioinosine, p-nitrobenzyl-6-selenopurine riboside, N(6)-(p-azidobenzyl)adenosine, and N(6)-(p-nitrobenzyl)adenosine, like NBMPR, were selectively toxic to parasite-infected cells. Thus, it appears that the unique characteristics of purine metabolism in T. gondii render certain 6-substituted 9-beta-D-ribofuranosylpurines promising antitoxoplasmic drugs.  (+info)

Characterization and molecular cloning of an adenosine kinase from Babesia canis rossi. (5/217)

In the search for immunoprotective antigens of the intraerythrocytic Babesia canis rossi parasite, a new cDNA was cloned and sequenced. Protein sequence database searches suggested that the 41-kDa protein belongs to the phosphofructokinase B type family (PFK-B). However, because of the low level sequence identity (< 20%) of the protein both with adenosine and sugar kinases from this family, its structural and functional features were further investigated using molecular modelling and enzymatic assays. The sequence/structure comparison of the protein with the crystal structure of a member of the PFK-B family, Escherichia coli ribokinase (EcRK), suggested that it might also form a stable and active dimer and revealed conservation of the ATP-binding site. However, residues specifically involved in the ribose-binding sites in the EcRK sequence (S and N) were substituted in its sequence (by H and M, respectively), and were suspected of binding adenosine compounds rather than sugar ones. Enzymatic assays using a purified glutathione S-transferase fusion protein revealed that this protein exhibits rapid catalysis of the phosphorylation of adenosine with an apparent Km value of 70 nM, whereas it was inactive on ribose or other carbohydrates. As enzymatic assays confirmed the results of the structure/function analysis indicating a preferential specificity towards adenosine compounds, this new protein of the PFK-B family corresponds to an adenosine kinase from B. canis rossi. It was named BcrAK.  (+info)

The adenosine transporter of Toxoplasma gondii. Identification by insertional mutagenesis, cloning, and recombinant expression. (6/217)

Purine transport into the protozoan parasite Toxoplasma gondii plays an indispensable nutritional function for this pathogen. To facilitate genetic and biochemical characterization of the adenosine transporter of the parasite, T. gondii tachyzoites were transfected with an insertional mutagenesis vector, and clonal mutants were selected for resistance to the cytotoxic adenosine analog adenine arabinoside (Ara-A). Whereas some Ara-A-resistant clones exhibited disruption of the adenosine kinase (AK) locus, others displayed normal AK activity, suggesting that a second locus had been tagged by the insertional mutagenesis plasmid. These Ara-A(r) AK+ mutants displayed reduced adenosine uptake capability, implying a defect in adenosine transport. Sequences flanking the transgene integration point in one mutant were rescued from a genomic library of Ara-A(r) AK+ DNA, and Southern blot analysis revealed that all Ara-A(r) AK+ mutants were disrupted at the same locus. Probes derived from this locus, designated TgAT, were employed to isolate genomic and cDNA clones from wild-type libraries. Conceptual translation of the TgAT cDNA open reading frame predicts a 462 amino acid protein containing 11 transmembrane domains, a primary structure and membrane topology similar to members of the mammalian equilibrative nucleoside transporter family. Expression of TgAT cRNA in Xenopus laevis oocytes increased adenosine uptake capacity in a saturable manner, with an apparent K(m) value of 114 microM. Uptake was inhibited by various nucleosides, nucleoside analogs, hypoxanthine, guanine, and dipyridamole. The combination of genetic and biochemical studies demonstrates that TgAT is the sole functional adenosine transporter in T. gondii and a rational target for therapeutic intervention.  (+info)

The influence of inorganic phosphate on the activity of adenosine kinase. (7/217)

The enzyme adenosine kinase (AK; EC 2.7.1.20) shows a dependence upon inorganic phosphate (Pi) for activity. The degree of dependence varies among enzyme sources and the pH at which the activity is measured. At physiological pH, recombinant AK from Chinese hamster ovary (CHO) cells and AK from beef liver (BL) show higher affinities for the substrate adenosine (Ado), larger maximum velocities and lower sensitivities to substrate inhibition in the presence of Pi. At pH 6.2, both BL and CHO AK exhibit almost complete dependence on the presence of Pi for activity. The data show that both enzymes exhibit increasing relief from substrate inhibition upon increasing Pi and the inhibition of BL AK is almost completely alleviated by the addition of 50 mM Pi. The affinity of CHO AK for Ado increases asymptotically from K(m) 6.4 microM to a limit of 0.7 microM upon the addition of increasing Pi from 1 to 50 mM. The concentration of Ado necessary to invoke substrate inhibition also increases asymptotically from K(i) 32 microM to a limit of 69 microM at saturating concentrations of phosphate. In the presence of increasing amounts of Pi, the maximal velocity of activity increases hyperbolically. The effect that phosphate exerts on AK may be either to protect the enzyme from inactivation at high adenosine and H(+) concentrations or to stabilize substrate binding at the active site.  (+info)

A(2B) receptors mediate antimitogenesis in vascular smooth muscle cells. (8/217)

Adenosine inhibits growth of vascular smooth muscle cells. The goals of this study were to determine which adenosine receptor subtype mediates the antimitogenic effects of adenosine and to investigate the signal transduction mechanisms involved. In rat aortic vascular smooth muscle cells, platelet-derived growth factor-BB (PDGF-BB) (25 ng/mL) stimulated DNA synthesis ([(3)H]thymidine incorporation), cellular proliferation (cell number), collagen synthesis ([(3)H]proline incorporation), total protein synthesis ([(3)H]leucine incorporation), and mitogen-activated protein (MAP) kinase activity. The adenosine receptor agonists 2-chloroadenosine and 5'-N-methylcarboxamidoadenosine, but not N(6)-cyclopentyladenosine or CGS21680, inhibited the growth effects of PDGF-BB, an agonist profile consistent with an A(2B) receptor-mediated effect. The adenosine receptor antagonists KF17837 and 1,3-dipropyl-8-p-sulfophenylxanthine, but not 8-cyclopentyl-1, 3-dipropylxanthine, blocked the growth-inhibitory effects of 2-chloroadenosine and 5'-N-methylcarboxamidoadenosine, an antagonist profile consistent with an A(2) receptor-mediated effect. Antisense, but not sense or scrambled, oligonucleotides to the A(2B) receptor stimulated basal and PDGF-induced DNA synthesis, cell proliferation, and MAP kinase activity. Moreover, the growth-inhibitory effects of 2-chloroadenosine, 5'-N-methylcarboxamidoadenosine, and erythro-9-(2-hydroxy-3-nonyl) adenine plus iodotubericidin (inhibitors of adenosine deaminase and adenosine kinase, respectively) were abolished by antisense, but not scrambled or sense, oligonucleotides to the A(2B) receptor. Our findings strongly support the hypothesis that adenosine causes inhibition of vascular smooth muscle cell growth by activating A(2B) receptors coupled to inhibition of MAP kinase activity. Pharmacological or molecular biological activation of A(2B) receptors may prevent vascular remodeling associated with hypertension, atherosclerosis, and restenosis following balloon angioplasty.  (+info)

Adenosine kinase (ADK) is an enzyme that plays a crucial role in the regulation of adenosine levels in cells. The medical definition of adenosine kinase is:

"An enzyme (EC 2.7.1.20) that catalyzes the phosphorylation of adenosine to form adenosine monophosphate (AMP) using ATP as the phosphate donor. This reaction helps maintain the balance between adenosine and its corresponding nucleotides in cells, and it plays a significant role in purine metabolism, cell signaling, and energy homeostasis."

Adenosine kinase is widely distributed in various tissues, including the brain, heart, liver, and muscles. Dysregulation of adenosine kinase activity has been implicated in several pathological conditions, such as ischemia-reperfusion injury, neurodegenerative disorders, and cancer. Therefore, modulating adenosine kinase activity has emerged as a potential therapeutic strategy for treating these diseases.

Adenosine is a purine nucleoside that is composed of a sugar (ribose) and the base adenine. It plays several important roles in the body, including serving as a precursor for the synthesis of other molecules such as ATP, NAD+, and RNA.

In the medical context, adenosine is perhaps best known for its use as a pharmaceutical agent to treat certain cardiac arrhythmias. When administered intravenously, it can help restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT) by slowing conduction through the atrioventricular node and interrupting the reentry circuit responsible for the arrhythmia.

Adenosine can also be used as a diagnostic tool to help differentiate between narrow-complex tachycardias of supraventricular origin and those that originate from below the ventricles (such as ventricular tachycardia). This is because adenosine will typically terminate PSVT but not affect the rhythm of VT.

It's worth noting that adenosine has a very short half-life, lasting only a few seconds in the bloodstream. This means that its effects are rapidly reversible and generally well-tolerated, although some patients may experience transient symptoms such as flushing, chest pain, or shortness of breath.

Tubercidin is not a medical term itself, but it is a type of antibiotic that belongs to the class of compounds known as nucleoside antibiotics. Specifically, tubercidin is a naturally occurring adenine analogue that is produced by several species of Streptomyces bacteria.

Tubercidin has been found to have antimicrobial and antitumor activities. It works by inhibiting the enzyme adenosine deaminase, which plays a crucial role in the metabolism of nucleotides in cells. By inhibiting this enzyme, tubercidin can interfere with DNA and RNA synthesis, leading to cell death.

While tubercidin has shown promise as an anticancer agent in preclinical studies, its clinical use is limited due to its toxicity and potential for causing mutations in normal cells. Therefore, it is primarily used for research purposes to study the mechanisms of nucleotide metabolism and the effects of nucleoside analogues on cell growth and differentiation.

Adenosine A2A receptor is a type of G protein-coupled receptor that binds to the endogenous purine nucleoside, adenosine. It is a subtype of the A2 receptor along with the A2B receptor and is widely distributed throughout the body, particularly in the brain, heart, and immune system.

The A2A receptor plays an essential role in various physiological processes, including modulation of neurotransmission, cardiovascular function, and immune response. In the brain, activation of A2A receptors can have both excitatory and inhibitory effects on neuronal activity, depending on the location and context.

In the heart, A2A receptor activation has a negative chronotropic effect, reducing heart rate, and a negative inotropic effect, decreasing contractility. In the immune system, A2A receptors are involved in regulating inflammation and immune cell function.

Pharmacologically, A2A receptor agonists have been investigated for their potential therapeutic benefits in various conditions, including Parkinson's disease, chronic pain, ischemia-reperfusion injury, and cancer. Conversely, A2A receptor antagonists have also been studied as a potential treatment for neurodegenerative disorders, such as Alzheimer's disease, and addiction.

Adenosine Deaminase (ADA) is an enzyme that plays a crucial role in the immune system by helping to regulate the levels of certain chemicals called purines within cells. Specifically, ADA helps to break down adenosine, a type of purine, into another compound called inosine. This enzyme is found in all tissues of the body, but it is especially active in the immune system's white blood cells, where it helps to support their growth, development, and function.

ADA deficiency is a rare genetic disorder that can lead to severe combined immunodeficiency (SCID), a condition in which babies are born with little or no functional immune system. This makes them extremely vulnerable to infections, which can be life-threatening. ADA deficiency can be treated with enzyme replacement therapy, bone marrow transplantation, or gene therapy.

Adenosine A1 receptor is a type of G protein-coupled receptor that binds to the endogenous purine nucleoside adenosine. When activated, it inhibits the production of cyclic AMP (cAMP) in the cell by inhibiting adenylyl cyclase activity. This results in various physiological effects, such as decreased heart rate and reduced force of heart contractions, increased potassium conductance, and decreased calcium currents. The Adenosine A1 receptor is widely distributed throughout the body, including the brain, heart, kidneys, and other organs. It plays a crucial role in various biological processes, including cardiovascular function, neuroprotection, and inflammation.

Adenosine deaminase inhibitors are a class of medications that work by blocking the action of the enzyme adenosine deaminase. This enzyme is responsible for breaking down adenosine, a chemical in the body that helps regulate the immune system and is involved in the inflammatory response.

By inhibiting the activity of adenosine deaminase, these medications can increase the levels of adenosine in the body. This can be useful in certain medical conditions where reducing inflammation is important. For example, adenosine deaminase inhibitors are sometimes used to treat rheumatoid arthritis, a chronic autoimmune disease characterized by inflammation and damage to the joints.

One common adenosine deaminase inhibitor is called deoxycoformycin (also known as pentostatin). This medication is typically given intravenously and is used to treat hairy cell leukemia, a rare type of cancer that affects white blood cells.

It's important to note that adenosine deaminase inhibitors can have serious side effects, including suppression of the immune system, which can make people more susceptible to infections. They should only be used under the close supervision of a healthcare provider.

Inosine is not a medical condition but a naturally occurring compound called a nucleoside, which is formed from the combination of hypoxanthine and ribose. It is an intermediate in the metabolic pathways of purine nucleotides, which are essential components of DNA and RNA. Inosine has been studied for its potential therapeutic benefits in various medical conditions, including neurodegenerative disorders, cardiovascular diseases, and cancer. However, more research is needed to fully understand its mechanisms and clinical applications.

Adenosine A2B receptor (A2BAR) is a type of G protein-coupled receptor that binds the endogenous purine nucleoside adenosine. It is a subtype of the A2 class of adenosine receptors, which also includes A2A receptor.

The A2BAR is widely expressed in various tissues and cells, including vascular smooth muscle cells, endothelial cells, fibroblasts, immune cells, and epithelial cells. Activation of the A2BAR by adenosine leads to a variety of cellular responses, such as relaxation of vascular smooth muscle, inhibition of platelet aggregation, modulation of inflammatory responses, and stimulation of fibroblast proliferation and collagen production.

The A2BAR has been implicated in several physiological and pathophysiological processes, such as cardiovascular function, pain perception, neuroprotection, tumor growth and metastasis, and pulmonary fibrosis. Therefore, the development of selective A2BAR agonists or antagonists has been an area of active research for therapeutic interventions in these conditions.

Adenosine monophosphate (AMP) is a nucleotide that is the monophosphate ester of adenosine, consisting of the nitrogenous base adenine attached to the 1' carbon atom of ribose via a β-N9-glycosidic bond, which in turn is esterified to a phosphate group. It is an important molecule in biological systems as it plays a key role in cellular energy transfer and storage, serving as a precursor to other nucleotides such as ADP and ATP. AMP is also involved in various signaling pathways and can act as a neurotransmitter in the central nervous system.

Purinergic P1 receptors are a type of G-protein coupled receptor that bind to nucleotides such as adenosine. These receptors are involved in a variety of physiological processes, including modulation of neurotransmitter release, cardiovascular function, and immune response. There are four subtypes of P1 receptors (A1, A2A, A2B, and A3) that have different signaling pathways and functions. Activation of these receptors can lead to a variety of cellular responses, including inhibition or stimulation of adenylyl cyclase activity, changes in intracellular calcium levels, and activation of various protein kinases. They play important roles in the central nervous system, cardiovascular system, respiratory system, gastrointestinal system, and immune system.

Adenosine A3 receptor (A3R) is a type of G-protein coupled receptor that binds to adenosine, a purine nucleoside, and plays a role in various physiological processes. The activation of A3R leads to the inhibition of adenylate cyclase activity, which results in decreased levels of intracellular cAMP. This, in turn, modulates several downstream signaling pathways that are involved in anti-inflammatory and neuroprotective effects.

A3R is widely expressed in various tissues, including the brain, heart, lungs, liver, kidneys, and immune cells. In the central nervous system, A3R activation has been shown to have neuroprotective effects, such as reducing glutamate release, protecting against excitotoxicity, and modulating neuroinflammation. Additionally, A3R agonists have been investigated for their potential therapeutic benefits in various pathological conditions, including pain management, ischemia-reperfusion injury, and neurodegenerative diseases.

Overall, the Adenosine A3 receptor is an important target for drug development due to its role in modulating inflammation and cellular responses in various tissues and diseases.

Adenosine A1 receptor antagonists are a class of pharmaceutical compounds that block the action of adenosine at A1 receptors. Adenosine is a naturally occurring purine nucleoside that acts as a neurotransmitter and modulator of various physiological processes, including cardiovascular function, neuronal excitability, and immune response.

Adenosine exerts its effects by binding to specific receptors on the surface of cells, including A1, A2A, A2B, and A3 receptors. The activation of A1 receptors leads to a variety of physiological responses, such as vasodilation, negative chronotropy (slowing of heart rate), and negative inotropy (reduced contractility) of the heart, as well as inhibition of neurotransmitter release in the brain.

Adenosine A1 receptor antagonists work by binding to and blocking the action of adenosine at A1 receptors, thereby preventing or reducing its effects on these physiological processes. These drugs have been investigated for their potential therapeutic uses in various conditions, such as heart failure, cardiac arrest, and neurological disorders.

Examples of adenosine A1 receptor antagonists include:

* Dipyridamole: a vasodilator used to treat peripheral arterial disease and to prevent blood clots.
* Caffeine: a natural stimulant found in coffee, tea, and chocolate, which acts as a weak A1 receptor antagonist.
* Rolofylline: an experimental drug that has been investigated for its potential use in treating acute ischemic stroke and traumatic brain injury.
* KW-3902: another experimental drug that has been studied for its potential therapeutic effects in heart failure, cardiac arrest, and neurodegenerative disorders.

It's important to note that adenosine A1 receptor antagonists may have side effects and potential risks, and their use should be monitored and managed by healthcare professionals.

5'-Nucleotidase is an enzyme that is found on the outer surface of cell membranes, including those of liver cells and red blood cells. Its primary function is to catalyze the hydrolysis of nucleoside monophosphates, such as adenosine monophosphate (AMP) and guanosine monophosphate (GMP), to their corresponding nucleosides, such as adenosine and guanosine, by removing a phosphate group from the 5' position of the nucleotide.

Abnormal levels of 5'-Nucleotidase in the blood can be indicative of liver or bone disease. For example, elevated levels of this enzyme in the blood may suggest liver damage or injury, such as that caused by hepatitis, cirrhosis, or alcohol abuse. Conversely, low levels of 5'-Nucleotidase may be associated with certain types of anemia, including aplastic anemia and paroxysmal nocturnal hemoglobinuria.

Medical professionals may order a 5'-Nucleotidase test to help diagnose or monitor the progression of these conditions. It is important to note that other factors, such as medication use or muscle damage, can also affect 5'-Nucleotidase levels, so results must be interpreted in conjunction with other clinical findings and diagnostic tests.

Formycins are a group of antibiotics that are derived from certain strains of Streptomyces bacteria. They include formycin B (also known as pyrazofurin), which is an antiviral and antimetabolite drug that works by interfering with the production of genetic material in cells. Formycins are not widely used in clinical medicine due to their potential toxicity and the availability of other effective antibiotics and antiviral drugs.

Ribonucleosides are organic compounds that consist of a nucleoside bound to a ribose sugar. Nucleosides are formed when a nitrogenous base (such as adenine, guanine, uracil, cytosine, or thymine) is attached to a sugar molecule (either ribose or deoxyribose) via a beta-glycosidic bond. In the case of ribonucleosides, the sugar component is D-ribose. Ribonucleosides play important roles in various biological processes, particularly in the storage, transfer, and expression of genetic information within cells. When ribonucleosides are phosphorylated, they become the building blocks of RNA (ribonucleic acid), a crucial biomolecule involved in protein synthesis and other cellular functions. Examples of ribonucleosides include adenosine, guanosine, uridine, cytidine, and inosine.

Phosphotransferases are a group of enzymes that catalyze the transfer of a phosphate group from a donor molecule to an acceptor molecule. This reaction is essential for various cellular processes, including energy metabolism, signal transduction, and biosynthesis.

The systematic name for this group of enzymes is phosphotransferase, which is derived from the general reaction they catalyze: D-donor + A-acceptor = D-donor minus phosphate + A-phosphate. The donor molecule can be a variety of compounds, such as ATP or a phosphorylated protein, while the acceptor molecule is typically a compound that becomes phosphorylated during the reaction.

Phosphotransferases are classified into several subgroups based on the type of donor and acceptor molecules they act upon. For example, kinases are a subgroup of phosphotransferases that transfer a phosphate group from ATP to a protein or other organic compound. Phosphatases, another subgroup, remove phosphate groups from molecules by transferring them to water.

Overall, phosphotransferases play a critical role in regulating many cellular functions and are important targets for drug development in various diseases, including cancer and neurological disorders.

Phosphatidylinositol 3-Kinases (PI3Ks) are a family of enzymes that play a crucial role in intracellular signal transduction. They phosphorylate the 3-hydroxyl group of the inositol ring in phosphatidylinositol and its derivatives, which results in the production of second messengers that regulate various cellular processes such as cell growth, proliferation, differentiation, motility, and survival.

PI3Ks are divided into three classes based on their structure and substrate specificity. Class I PI3Ks are further subdivided into two categories: class IA and class IB. Class IA PI3Ks are heterodimers consisting of a catalytic subunit (p110α, p110β, or p110δ) and a regulatory subunit (p85α, p85β, p55γ, or p50γ). They are primarily activated by receptor tyrosine kinases and G protein-coupled receptors. Class IB PI3Ks consist of a catalytic subunit (p110γ) and a regulatory subunit (p101 or p84/87). They are mainly activated by G protein-coupled receptors.

Dysregulation of PI3K signaling has been implicated in various human diseases, including cancer, diabetes, and autoimmune disorders. Therefore, PI3Ks have emerged as important targets for drug development in these areas.

Mitogen-activated protein kinase (MAPK) signaling system is a crucial pathway for the transmission and regulation of various cellular responses in eukaryotic cells. It plays a significant role in several biological processes, including proliferation, differentiation, apoptosis, inflammation, and stress response. The MAPK cascade consists of three main components: MAP kinase kinase kinase (MAP3K or MEKK), MAP kinase kinase (MAP2K or MEK), and MAP kinase (MAPK).

The signaling system is activated by various extracellular stimuli, such as growth factors, cytokines, hormones, and stress signals. These stimuli initiate a phosphorylation cascade that ultimately leads to the activation of MAPKs. The activated MAPKs then translocate into the nucleus and regulate gene expression by phosphorylating various transcription factors and other regulatory proteins.

There are four major MAPK families: extracellular signal-regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNK1/2/3), p38 MAPKs (p38α/β/γ/δ), and ERK5. Each family has distinct functions, substrates, and upstream activators. Dysregulation of the MAPK signaling system can lead to various diseases, including cancer, diabetes, cardiovascular diseases, and neurological disorders. Therefore, understanding the molecular mechanisms underlying this pathway is crucial for developing novel therapeutic strategies.

Protein kinases are a group of enzymes that play a crucial role in many cellular processes by adding phosphate groups to other proteins, a process known as phosphorylation. This modification can activate or deactivate the target protein's function, thereby regulating various signaling pathways within the cell. Protein kinases are essential for numerous biological functions, including metabolism, signal transduction, cell cycle progression, and apoptosis (programmed cell death). Abnormal regulation of protein kinases has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

Adenosine A2 receptors are a type of G-protein coupled receptor that binds the endogenous purine nucleoside adenosine. They are divided into two subtypes, A2a and A2b, which have different distributions in the body and couple to different G proteins.

A2a receptors are found in high levels in the brain, particularly in the striatum, and play a role in regulating the release of neurotransmitters such as dopamine and glutamate. They also have anti-inflammatory effects and are being studied as potential targets for the treatment of neurological disorders such as Parkinson's disease and multiple sclerosis.

A2b receptors, on the other hand, are found in a variety of tissues including the lung, blood vessels, and immune cells. They play a role in regulating inflammation and vasodilation, and have been implicated in the development of conditions such as asthma and pulmonary fibrosis.

Both A2a and A2b receptors are activated by adenosine, which is released in response to cellular stress or injury. Activation of these receptors can lead to a variety of downstream effects, depending on the tissue and context in which they are expressed.

Pentostatin is a medication used in the treatment of certain types of cancer, including hairy cell leukemia and certain T-cell lymphomas. It is a type of drug called a purine nucleoside analog, which works by interfering with the production of DNA and RNA, the genetic material found in cells. This can help to stop the growth and multiplication of cancer cells.

Pentostatin is given intravenously (through an IV) in a healthcare setting, such as a hospital or clinic. It is usually administered on a schedule of every other week. Common side effects of pentostatin include nausea, vomiting, diarrhea, and loss of appetite. It can also cause more serious side effects, such as low blood cell counts, infections, and liver problems.

It's important to note that this is a medical definition of the drug and its use, and it should not be used as a substitute for professional medical advice. If you have any questions about pentostatin or your treatment, it is best to speak with your healthcare provider.

Protein-Serine-Threonine Kinases (PSTKs) are a type of protein kinase that catalyzes the transfer of a phosphate group from ATP to the hydroxyl side chains of serine or threonine residues on target proteins. This phosphorylation process plays a crucial role in various cellular signaling pathways, including regulation of metabolism, gene expression, cell cycle progression, and apoptosis. PSTKs are involved in many physiological and pathological processes, and their dysregulation has been implicated in several diseases, such as cancer, diabetes, and neurodegenerative disorders.

Adenosine A2 receptor agonists are pharmaceutical agents that bind to and activate the A2 subtype of adenosine receptors, which are G-protein coupled receptors found in various tissues throughout the body. Activation of these receptors leads to a variety of physiological effects, including vasodilation, increased coronary blood flow, and inhibition of platelet aggregation.

A2 receptor agonists have been studied for their potential therapeutic benefits in several medical conditions, such as:

1. Heart failure: A2 receptor agonists can improve cardiac function and reduce symptoms in patients with heart failure by increasing coronary blood flow and reducing oxygen demand.
2. Atrial fibrillation: These agents have been shown to terminate or prevent atrial fibrillation, a common abnormal heart rhythm disorder, through their effects on the electrical properties of cardiac cells.
3. Asthma and COPD: A2 receptor agonists can help relax airway smooth muscle and reduce inflammation in patients with asthma and chronic obstructive pulmonary disease (COPD).
4. Pain management: Some A2 receptor agonists have been found to have analgesic properties, making them potential candidates for pain relief in various clinical settings.

Examples of A2 receptor agonists include regadenoson, which is used as a pharmacological stress agent during myocardial perfusion imaging, and dipyridamole, which is used to prevent blood clots in patients with certain heart conditions. However, it's important to note that these agents can have side effects, such as hypotension, bradycardia, and bronchoconstriction, so their use must be carefully monitored and managed by healthcare professionals.

Inosine monophosphate (IMP) is a nucleotide that plays a crucial role in the metabolic pathways of energy production and purine synthesis in cells. It is an ester of the nucleoside inosine and phosphoric acid. IMP is an important intermediate in the conversion of adenosine monophosphate (AMP) to guanosine monophosphate (GMP) in the purine nucleotide cycle, which is critical for maintaining the balance of purine nucleotides in the body. Additionally, IMP can be converted back to AMP through the action of the enzyme adenylosuccinate lyase. IMP has been studied for its potential therapeutic benefits in various medical conditions, including neurodegenerative disorders and ischemia-reperfusion injury.

Purinergic P1 receptor antagonists are a class of pharmaceutical drugs that block the activity of purinergic P1 receptors, which are a type of G-protein coupled receptor found in many tissues throughout the body. These receptors are activated by extracellular nucleotides such as adenosine and ATP, and play important roles in regulating a variety of physiological processes, including cardiovascular function, neurotransmission, and immune response.

Purinergic P1 receptor antagonists work by binding to these receptors and preventing them from being activated by nucleotides. This can have various therapeutic effects, depending on the specific receptor subtype that is targeted. For example, A1 receptor antagonists have been shown to improve cardiac function in heart failure, while A2A receptor antagonists have potential as anti-inflammatory and neuroprotective agents.

However, it's important to note that the use of purinergic P1 receptor antagonists is still an area of active research, and more studies are needed to fully understand their mechanisms of action and therapeutic potential.

Deoxyadenosine is a chemical compound that is a component of DNA, one of the nucleic acids that make up the genetic material of living organisms. Specifically, deoxyadenosine is a nucleoside, which is a molecule consisting of a sugar (in this case, deoxyribose) bonded to a nitrogenous base (in this case, adenine).

Deoxyribonucleosides like deoxyadenosine are the building blocks of DNA, along with phosphate groups. In DNA, deoxyadenosine pairs with thymidine via hydrogen bonds to form one of the four rungs in the twisted ladder structure of the double helix.

It is important to note that there is a similar compound called adenosine, which contains an extra oxygen atom on the sugar molecule (making it a ribonucleoside) and is a component of RNA, another nucleic acid involved in protein synthesis and other cellular processes.

Adenosine A2 receptor antagonists are a class of pharmaceutical compounds that block the action of adenosine at A2 receptors. Adenosine is a naturally occurring molecule in the body that acts as a neurotransmitter and has various physiological effects, including vasodilation and inhibition of heart rate.

Adenosine A2 receptor antagonists work by binding to A2 receptors and preventing adenosine from activating them. This results in the opposite effect of adenosine, leading to vasoconstriction and increased heart rate. These drugs are used for a variety of medical conditions, including asthma, chronic obstructive pulmonary disease (COPD), and heart failure.

Examples of Adenosine A2 receptor antagonists include theophylline, caffeine, and some newer drugs such asistradefylline and tozadenant. These drugs have different pharmacological properties and are used for specific medical conditions. It is important to note that adenosine A2 receptor antagonists can have side effects, including restlessness, insomnia, and gastrointestinal symptoms, and should be used under the guidance of a healthcare professional.

Zeatin is not a medical term per se, but it is a significant compound in the field of plant biology and agriculture. It is a type of cytokinin, which is a class of hormones that play crucial roles in plant growth and development. Specifically, zeatin is involved in cell division, differentiation, and delaying senescence (aging) in plants.

In a broader biological context, understanding the functions of phytohormones like zeatin can have implications for agricultural practices and crop management, which may indirectly impact human health through improved food production and quality.

2-Chloroadenosine is a synthetic, chlorinated analog of adenosine, which is a naturally occurring purine nucleoside. It acts as an antagonist at adenosine receptors and has been studied for its potential effects on the cardiovascular system, including its ability to reduce heart rate and blood pressure. It may also have anti-cancer properties and has been investigated as a potential therapeutic agent in cancer treatment. However, further research is needed to establish its safety and efficacy in clinical settings.

Xanthines are a type of natural alkaloids that are found in various plants, including tea leaves, cocoa beans, and mate. The most common xanthines are caffeine, theophylline, and theobromine. These compounds have stimulant effects on the central nervous system and are often used in medication to treat conditions such as asthma, bronchitis, and other respiratory issues.

Caffeine is the most widely consumed xanthine and is found in a variety of beverages like coffee, tea, and energy drinks. It works by blocking adenosine receptors in the brain, which can lead to increased alertness and reduced feelings of fatigue.

Theophylline is another xanthine that is used as a bronchodilator to treat asthma and other respiratory conditions. It works by relaxing smooth muscles in the airways, making it easier to breathe.

Theobromine is found in cocoa beans and is responsible for the stimulant effects of chocolate. While it has similar properties to caffeine and theophylline, it is less potent and has a milder effect on the body.

It's worth noting that while xanthines can have beneficial effects when used in moderation, they can also cause negative side effects such as insomnia, nervousness, and rapid heart rate if consumed in large quantities or over an extended period of time.

Coformycin is an antimetabolite antibiotic, which means it interferes with the growth of bacteria by inhibiting the synthesis of nucleic acids, the genetic material of bacteria. It is derived from Streptomyces coelicolor and is used primarily in research to study bacterial metabolism.

Coformycin is a potent inhibitor of bacterial enzyme adenosine deaminase, which is involved in purine biosynthesis. By inhibiting this enzyme, Coformycin prevents the bacteria from synthesizing the building blocks needed to make DNA and RNA, thereby inhibiting their growth.

Coformycin has not been approved for use as a therapeutic drug in humans or animals due to its narrow spectrum of activity and potential toxicity. However, it is still used in research settings to study bacterial metabolism and the mechanisms of antibiotic resistance.

Nucleotidases are a class of enzymes that catalyze the hydrolysis of nucleotides into nucleosides and phosphate groups. Nucleotidases play important roles in various biological processes, including the regulation of nucleotide concentrations within cells, the salvage pathways for nucleotide synthesis, and the breakdown of nucleic acids during programmed cell death (apoptosis).

There are several types of nucleotidases that differ in their substrate specificity and subcellular localization. These include:

1. Nucleoside monophosphatases (NMPs): These enzymes hydrolyze nucleoside monophosphates (NMPs) into nucleosides and inorganic phosphate.
2. Nucleoside diphosphatases (NDPs): These enzymes hydrolyze nucleoside diphosphates (NDPs) into nucleoside monophosphates (NMPs) and inorganic phosphate.
3. Nucleoside triphosphatases (NTPs): These enzymes hydrolyze nucleoside triphosphates (NTPs) into nucleoside diphosphates (NDPs) and inorganic phosphate.
4. 5'-Nucleotidase: This enzyme specifically hydrolyzes the phosphate group from the 5' position of nucleoside monophosphates, producing nucleosides.
5. Pyrophosphatases: These enzymes hydrolyze pyrophosphates into two phosphate groups and play a role in regulating nucleotide metabolism.

Nucleotidases are widely distributed in nature and can be found in various tissues, organs, and biological fluids, including blood, urine, and cerebrospinal fluid. Dysregulation of nucleotidase activity has been implicated in several diseases, such as cancer, neurodegenerative disorders, and infectious diseases.

Thioinosine is not a medical term itself, but it is a chemical compound that has been studied in the field of medical research. Thioinosine is an analogue of the nucleoside inosine, where the oxygen atom in the heterocyclic ring is replaced by a sulfur atom.

In the context of medical research, thioinosine has been investigated for its potential immunomodulatory and antiviral properties. It has been studied as an inhibitor of certain enzymes involved in the replication of viruses, such as HIV and hepatitis C virus. However, it is not currently approved for use as a medication in clinical practice.

Adenosine A1 receptor agonists are medications or substances that bind to and activate the adenosine A1 receptors, which are found on the surface of certain cells in the body, including those in the heart, brain, and other organs.

Adenosine is a naturally occurring molecule in the body that helps regulate various physiological processes, such as cardiovascular function and neurotransmission. The adenosine A1 receptor plays an important role in modulating the activity of the heart, including reducing heart rate and lowering blood pressure.

Adenosine A1 receptor agonists are used clinically to treat certain medical conditions, such as supraventricular tachycardia (a rapid heart rhythm originating from above the ventricles), and to prevent cerebral vasospasm (narrowing of blood vessels in the brain) following subarachnoid hemorrhage.

Examples of adenosine A1 receptor agonists include adenosine, regadenoson, and capadenoson. These medications work by mimicking the effects of naturally occurring adenosine on the A1 receptors, leading to a decrease in heart rate and blood pressure.

It's important to note that adenosine A1 receptor agonists can have side effects, such as chest pain, shortness of breath, and flushing, which are usually transient and mild. However, they should be used with caution and under the supervision of a healthcare professional, as they can also have more serious side effects in certain individuals.

Methylthioinosine is not a widely recognized or used term in medicine, and it does not have a specific medical definition. It is a chemical compound that is formed by the addition of a methylthio group (-CH3S-) to the nucleoside inosine. Inosine is a purine nucleoside that is formed from the deamination of adenosine.

Methylthioinosine has been studied in some laboratory experiments, but it is not commonly used in clinical medicine or treatment. Therefore, it is not a term that most medical professionals would be familiar with.

Protein kinase inhibitors (PKIs) are a class of drugs that work by interfering with the function of protein kinases. Protein kinases are enzymes that play a crucial role in many cellular processes by adding a phosphate group to specific proteins, thereby modifying their activity, localization, or interaction with other molecules. This process of adding a phosphate group is known as phosphorylation and is a key mechanism for regulating various cellular functions, including signal transduction, metabolism, and cell division.

In some diseases, such as cancer, protein kinases can become overactive or mutated, leading to uncontrolled cell growth and division. Protein kinase inhibitors are designed to block the activity of these dysregulated kinases, thereby preventing or slowing down the progression of the disease. These drugs can be highly specific, targeting individual protein kinases or families of kinases, making them valuable tools for targeted therapy in cancer and other diseases.

Protein kinase inhibitors can work in various ways to block the activity of protein kinases. Some bind directly to the active site of the enzyme, preventing it from interacting with its substrates. Others bind to allosteric sites, changing the conformation of the enzyme and making it inactive. Still, others target upstream regulators of protein kinases or interfere with their ability to form functional complexes.

Examples of protein kinase inhibitors include imatinib (Gleevec), which targets the BCR-ABL kinase in chronic myeloid leukemia, and gefitinib (Iressa), which inhibits the EGFR kinase in non-small cell lung cancer. These drugs have shown significant clinical benefits in treating these diseases and have become important components of modern cancer therapy.

Calcium-calmodulin-dependent protein kinases (CAMKs) are a family of enzymes that play a crucial role in intracellular signaling pathways. They are activated by the binding of calcium ions and calmodulin, a ubiquitous calcium-binding protein, to their regulatory domain.

Once activated, CAMKs phosphorylate specific serine or threonine residues on target proteins, thereby modulating their activity, localization, or stability. This post-translational modification is essential for various cellular processes, including synaptic plasticity, gene expression, metabolism, and cell cycle regulation.

There are several subfamilies of CAMKs, including CaMKI, CaMKII, CaMKIII (also known as CaMKIV), and CaMK kinase (CaMKK). Each subfamily has distinct structural features, substrate specificity, and regulatory mechanisms. Dysregulation of CAMK signaling has been implicated in various pathological conditions, such as neurodegenerative diseases, cancer, and cardiovascular disorders.

Hypoxanthine is a purine derivative and an intermediate in the metabolic pathways of nucleotide degradation, specifically adenosine to uric acid in humans. It is formed from the oxidation of xanthine by the enzyme xanthine oxidase. In the body, hypoxanthine is converted to xanthine and then to uric acid, which is excreted in the urine. Increased levels of hypoxanthine in the body can be indicative of various pathological conditions, including tissue hypoxia, ischemia, and necrosis.

I must clarify that "Inorganic Chemicals" is a broad term related to the field of chemistry and not specifically within the realm of medicine. However, I can provide a general definition for you:

Inorganic chemicals are chemical substances that primarily consist of matter other than carbon-based compounds. They include metallic and non-metallic elements, along with their compounds, excluding carbon-hydrogen bonds (organic compounds). Examples of inorganic chemicals are salts, acids, and bases, as well as metal alloys and oxides.

In the context of medicine, certain inorganic chemicals can be used in medical treatments, such as lithium carbonate for bipolar disorder or potassium chloride as an electrolyte replenisher. However, some inorganic chemicals can also pose health risks depending on the type and level of exposure. For instance, lead and mercury are toxic heavy metals that can cause serious health problems if ingested or inhaled.

Adenosylhomocysteinase is an enzyme that plays a crucial role in the methionine cycle, which is a biochemical pathway involved in the synthesis and metabolism of various essential molecules in the body. The formal medical definition of adenosylhomocysteinase is:

"An enzyme that catalyzes the reversible conversion of S-adenosylhomocysteine to homocysteine and adenosine. This reaction is the first step in the recycling of methionine, a sulfur-containing amino acid that is essential for various metabolic processes, including the synthesis of proteins, neurotransmitters, and phospholipids."

In simpler terms, adenosylhomocysteinase helps break down S-adenosylhomocysteine, a byproduct of methylation reactions in the body, into its component parts: homocysteine and adenosine. This breakdown is essential for the proper functioning of the methionine cycle and the maintenance of normal levels of homocysteine, which can be toxic at high concentrations.

Deficiencies or mutations in the adenosylhomocysteinase gene can lead to an accumulation of S-adenosylhomocysteine and homocysteine, which can contribute to various health issues, including neurological disorders, cardiovascular disease, and developmental abnormalities.

Nucleoside deaminases are a group of enzymes that catalyze the removal of an amino group (-NH2) from nucleosides, converting them to nucleosides with a modified base. This modification process is called deamination. Specifically, these enzymes convert cytidine and adenosine to uridine and inosine, respectively. Nucleoside deaminases play crucial roles in various biological processes, including the regulation of gene expression, immune response, and nucleic acid metabolism. Some nucleoside deaminases are also involved in the development of certain diseases and are considered as targets for drug design and discovery.

A nucleoside is a biochemical molecule that consists of a pentose sugar (a type of simple sugar with five carbon atoms) covalently linked to a nitrogenous base. The nitrogenous base can be one of several types, including adenine, guanine, cytosine, thymine, or uracil. Nucleosides are important components of nucleic acids, such as DNA and RNA, which are the genetic materials found in cells. They play a crucial role in various biological processes, including cell division, protein synthesis, and gene expression.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

SRC-family kinases (SFKs) are a group of non-receptor tyrosine kinases that play important roles in various cellular processes, including cell proliferation, differentiation, survival, and migration. They are named after the founding member, SRC, which was first identified as an oncogene in Rous sarcoma virus.

SFKs share a common structure, consisting of an N-terminal unique domain, a SH3 domain, a SH2 domain, a catalytic kinase domain, and a C-terminal regulatory tail with a negative regulatory tyrosine residue (Y527 in human SRC). In their inactive state, SFKs are maintained in a closed conformation through intramolecular interactions between the SH3 domain, SH2 domain, and the phosphorylated C-terminal tyrosine.

Upon activation by various signals, such as growth factors, cytokines, or integrin engagement, SFKs are activated through a series of events that involve dephosphorylation of the regulatory tyrosine residue, recruitment to membrane receptors via their SH2 and SH3 domains, and trans-autophosphorylation of the activation loop in the kinase domain.

Once activated, SFKs can phosphorylate a wide range of downstream substrates, including other protein kinases, adaptor proteins, and cytoskeletal components, thereby regulating various signaling pathways that control cell behavior. Dysregulation of SFK activity has been implicated in various diseases, including cancer, inflammation, and neurological disorders.

Hypoxanthine is not a medical condition but a purine base that is a component of many organic compounds, including nucleotides and nucleic acids, which are the building blocks of DNA and RNA. In the body, hypoxanthine is produced as a byproduct of normal cellular metabolism and is converted to xanthine and then uric acid, which is excreted in the urine.

However, abnormally high levels of hypoxanthine in the body can indicate tissue damage or disease. For example, during intense exercise or hypoxia (low oxygen levels), cells may break down ATP (adenosine triphosphate) rapidly, releasing large amounts of hypoxanthine. Similarly, in some genetic disorders such as Lesch-Nyhan syndrome, there is an accumulation of hypoxanthine due to a deficiency of the enzyme that converts it to xanthine. High levels of hypoxanthine can lead to the formation of kidney stones and other complications.

Adenine nucleotides are molecules that consist of a nitrogenous base called adenine, which is linked to a sugar molecule (ribose in the case of adenosine monophosphate or AMP, and deoxyribose in the case of adenosine diphosphate or ADP and adenosine triphosphate or ATP) and one, two, or three phosphate groups. These molecules play a crucial role in energy transfer and metabolism within cells.

AMP contains one phosphate group, while ADP contains two phosphate groups, and ATP contains three phosphate groups. When a phosphate group is removed from ATP, energy is released, which can be used to power various cellular processes such as muscle contraction, nerve impulse transmission, and protein synthesis. The reverse reaction, in which a phosphate group is added back to ADP or AMP to form ATP, requires energy input and often involves the breakdown of nutrients such as glucose or fatty acids.

In addition to their role in energy metabolism, adenine nucleotides also serve as precursors for other important molecules, including DNA and RNA, coenzymes, and signaling molecules.

S-Adenosylhomocysteine (SAH) is a metabolic byproduct formed from the demethylation of various compounds or from the breakdown of S-adenosylmethionine (SAM), which is a major methyl group donor in the body. SAH is rapidly hydrolyzed to homocysteine and adenosine by the enzyme S-adenosylhomocysteine hydrolase. Increased levels of SAH can inhibit many methyltransferases, leading to disturbances in cellular metabolism and potential negative health effects.

Protein Kinase C (PKC) is a family of serine-threonine kinases that play crucial roles in various cellular signaling pathways. These enzymes are activated by second messengers such as diacylglycerol (DAG) and calcium ions (Ca2+), which result from the activation of cell surface receptors like G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs).

Once activated, PKC proteins phosphorylate downstream target proteins, thereby modulating their activities. This regulation is involved in numerous cellular processes, including cell growth, differentiation, apoptosis, and membrane trafficking. There are at least 10 isoforms of PKC, classified into three subfamilies based on their second messenger requirements and structural features: conventional (cPKC; α, βI, βII, and γ), novel (nPKC; δ, ε, η, and θ), and atypical (aPKC; ζ and ι/λ). Dysregulation of PKC signaling has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

Cyclic AMP (cAMP)-dependent protein kinases, also known as protein kinase A (PKA), are a family of enzymes that play a crucial role in intracellular signaling pathways. These enzymes are responsible for the regulation of various cellular processes, including metabolism, gene expression, and cell growth and differentiation.

PKA is composed of two regulatory subunits and two catalytic subunits. When cAMP binds to the regulatory subunits, it causes a conformational change that leads to the dissociation of the catalytic subunits. The freed catalytic subunits then phosphorylate specific serine and threonine residues on target proteins, thereby modulating their activity.

The cAMP-dependent protein kinases are activated in response to a variety of extracellular signals, such as hormones and neurotransmitters, that bind to G protein-coupled receptors (GPCRs) or receptor tyrosine kinases (RTKs). These signals lead to the activation of adenylyl cyclase, which catalyzes the conversion of ATP to cAMP. The resulting increase in intracellular cAMP levels triggers the activation of PKA and the downstream phosphorylation of target proteins.

Overall, cAMP-dependent protein kinases are essential regulators of many fundamental cellular processes and play a critical role in maintaining normal physiology and homeostasis. Dysregulation of these enzymes has been implicated in various diseases, including cancer, diabetes, and neurological disorders.

Purinergic P1 receptor agonists are substances that bind to and activate purinergic P1 receptors, which are a type of G protein-coupled receptor found in many tissues throughout the body. These receptors are activated by endogenous nucleotides such as adenosine and its metabolites.

Purinergic P1 receptors include four subtypes: A1, A2A, A2B, and A3. Each of these subtypes has distinct signaling pathways and physiological roles. For example, A1 receptor activation can lead to vasodilation, bradycardia, and anti-inflammatory effects, while A2A receptor activation can increase cyclic AMP levels and have anti-inflammatory effects.

Purinergic P1 receptor agonists are used in various therapeutic applications, including as cardiovascular drugs, antiplatelet agents, and anti-inflammatory agents. Some examples of purinergic P1 receptor agonists include adenosine, regadenoson, and dipyridamole.

It's important to note that the use of these substances should be under medical supervision due to their potential side effects and interactions with other medications.

Adenine is a purine nucleotide base that is a fundamental component of DNA and RNA, the genetic material of living organisms. In DNA, adenine pairs with thymine via double hydrogen bonds, while in RNA, it pairs with uracil. Adenine is essential for the structure and function of nucleic acids, as well as for energy transfer reactions in cells through its role in the formation of adenosine triphosphate (ATP), the primary energy currency of the cell.

Purines are heterocyclic aromatic organic compounds that consist of a pyrimidine ring fused to an imidazole ring. They are fundamental components of nucleotides, which are the building blocks of DNA and RNA. In the body, purines can be synthesized endogenously or obtained through dietary sources such as meat, seafood, and certain vegetables.

Once purines are metabolized, they are broken down into uric acid, which is excreted by the kidneys. Elevated levels of uric acid in the body can lead to the formation of uric acid crystals, resulting in conditions such as gout or kidney stones. Therefore, maintaining a balanced intake of purine-rich foods and ensuring proper kidney function are essential for overall health.

p38 Mitogen-Activated Protein Kinases (p38 MAPKs) are a family of conserved serine-threonine protein kinases that play crucial roles in various cellular processes, including inflammation, immune response, differentiation, apoptosis, and stress responses. They are activated by diverse stimuli such as cytokines, ultraviolet radiation, heat shock, osmotic stress, and lipopolysaccharides (LPS).

Once activated, p38 MAPKs phosphorylate and regulate several downstream targets, including transcription factors and other protein kinases. This regulation leads to the expression of genes involved in inflammation, cell cycle arrest, and apoptosis. Dysregulation of p38 MAPK signaling has been implicated in various diseases, such as cancer, neurodegenerative disorders, and autoimmune diseases. Therefore, p38 MAPKs are considered promising targets for developing new therapeutic strategies to treat these conditions.

Nucleotides are the basic structural units of nucleic acids, such as DNA and RNA. They consist of a nitrogenous base (adenine, guanine, cytosine, thymine or uracil), a pentose sugar (ribose in RNA and deoxyribose in DNA) and one to three phosphate groups. Nucleotides are linked together by phosphodiester bonds between the sugar of one nucleotide and the phosphate group of another, forming long chains known as polynucleotides. The sequence of these nucleotides determines the genetic information carried in DNA and RNA, which is essential for the functioning, reproduction and survival of all living organisms.

'Leishmania donovani' is a species of protozoan parasite that causes a severe form of visceral leishmaniasis, also known as kala-azar. This disease primarily affects the spleen, liver, and bone marrow, leading to symptoms such as fever, weight loss, anemia, and enlargement of the spleen and liver. The parasite is transmitted to humans through the bite of infected female sandflies. It's worth noting that this organism can also affect dogs and other animals, causing a disease known as canine leishmaniasis.

Mitogen-Activated Protein Kinase 1 (MAPK1), also known as Extracellular Signal-Regulated Kinase 2 (ERK2), is a protein kinase that plays a crucial role in intracellular signal transduction pathways. It is a member of the MAPK family, which regulates various cellular processes such as proliferation, differentiation, apoptosis, and stress response.

MAPK1 is activated by a cascade of phosphorylation events initiated by upstream activators like MAPKK (Mitogen-Activated Protein Kinase Kinase) in response to various extracellular signals such as growth factors, hormones, and mitogens. Once activated, MAPK1 phosphorylates downstream targets, including transcription factors and other protein kinases, thereby modulating their activities and ultimately influencing gene expression and cellular responses.

MAPK1 is widely expressed in various tissues and cells, and its dysregulation has been implicated in several pathological conditions, including cancer, inflammation, and neurodegenerative diseases. Therefore, understanding the regulation and function of MAPK1 signaling pathways has important implications for developing therapeutic strategies to treat these disorders.

Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.

Enzyme inhibitors are substances that bind to an enzyme and decrease its activity, preventing it from catalyzing a chemical reaction in the body. They can work by several mechanisms, including blocking the active site where the substrate binds, or binding to another site on the enzyme to change its shape and prevent substrate binding. Enzyme inhibitors are often used as drugs to treat various medical conditions, such as high blood pressure, abnormal heart rhythms, and bacterial infections. They can also be found naturally in some foods and plants, and can be used in research to understand enzyme function and regulation.

Substrate specificity in the context of medical biochemistry and enzymology refers to the ability of an enzyme to selectively bind and catalyze a chemical reaction with a particular substrate (or a group of similar substrates) while discriminating against other molecules that are not substrates. This specificity arises from the three-dimensional structure of the enzyme, which has evolved to match the shape, charge distribution, and functional groups of its physiological substrate(s).

Substrate specificity is a fundamental property of enzymes that enables them to carry out highly selective chemical transformations in the complex cellular environment. The active site of an enzyme, where the catalysis takes place, has a unique conformation that complements the shape and charge distribution of its substrate(s). This ensures efficient recognition, binding, and conversion of the substrate into the desired product while minimizing unwanted side reactions with other molecules.

Substrate specificity can be categorized as:

1. Absolute specificity: An enzyme that can only act on a single substrate or a very narrow group of structurally related substrates, showing no activity towards any other molecule.
2. Group specificity: An enzyme that prefers to act on a particular functional group or class of compounds but can still accommodate minor structural variations within the substrate.
3. Broad or promiscuous specificity: An enzyme that can act on a wide range of structurally diverse substrates, albeit with varying catalytic efficiencies.

Understanding substrate specificity is crucial for elucidating enzymatic mechanisms, designing drugs that target specific enzymes or pathways, and developing biotechnological applications that rely on the controlled manipulation of enzyme activities.

P21-activated kinases (PAKs) are a family of serine/threonine protein kinases that play crucial roles in various cellular processes, including cytoskeletal reorganization, cell motility, and gene transcription. They are activated by binding to small GTPases of the Rho family, such as Cdc42 and Rac, which become active upon stimulation of various extracellular signals. Once activated, PAKs phosphorylate a range of downstream targets, leading to changes in cell behavior and function. Aberrant regulation of PAKs has been implicated in several human diseases, including cancer and neurological disorders.

I'm sorry for any confusion, but "Toyocamycin" does not appear to be a recognized term in medical literature or pharmacology. It's possible that there may be a spelling error or it could be a very specialized or obscure term that is not widely known. I would recommend checking the spelling and, if necessary, consulting a specific scientific or medical text or expert for further clarification.

The foreskin is a double-layered fold of skin that covers and protects the head (glans) of the penis. It is a normal part of male anatomy and varies in length and coverage from person to person. The inner layer of the foreskin is highly sensitive and contains a high concentration of nerve endings, which can contribute to sexual pleasure.

In some cases, the foreskin may become tight or difficult to retract (a condition known as phimosis), which can cause discomfort or pain during sexual activity or other activities that stretch the foreskin. In these cases, medical intervention may be necessary to alleviate the problem. Some people choose to undergo circumcision, a surgical procedure in which the foreskin is removed, for cultural, religious, or personal reasons. However, circumcision is not medically necessary for most people and carries some risks, such as infection, bleeding, and scarring.

JNK (c-Jun N-terminal kinase) Mitogen-Activated Protein Kinases are a subgroup of the Ser/Thr protein kinases that are activated by stress stimuli and play important roles in various cellular processes, including inflammation, apoptosis, and differentiation. They are involved in the regulation of gene expression through phosphorylation of transcription factors such as c-Jun. JNKs are activated by a variety of upstream kinases, including MAP2Ks (MKK4/SEK1 and MKK7), which are in turn activated by MAP3Ks (such as ASK1, MEKK1, MLKs, and TAK1). JNK signaling pathways have been implicated in various diseases, including cancer, neurodegenerative disorders, and inflammatory diseases.

Mitogen-Activated Protein Kinase Kinases (MAP2K or MEK) are a group of protein kinases that play a crucial role in intracellular signal transduction pathways. They are so named because they are activated by mitogens, which are substances that stimulate cell division, and other extracellular signals.

MAP2Ks are positioned upstream of the Mitogen-Activated Protein Kinases (MAPK) in a three-tiered kinase cascade. Once activated, MAP2Ks phosphorylate and activate MAPKs, which then go on to regulate various cellular processes such as proliferation, differentiation, survival, and apoptosis.

There are several subfamilies of MAP2Ks, including MEK1/2, MEK3/6 (also known as MKK3/6), MEK4/7 (also known as MKK4/7), and MEK5. Each MAP2K is specific to activating a particular MAPK, and they are activated by different MAP3Ks (MAP kinase kinase kinases) in response to various extracellular signals.

Dysregulation of the MAPK/MAP2K signaling pathways has been implicated in numerous diseases, including cancer, cardiovascular disease, and neurological disorders. Therefore, targeting these pathways with therapeutic agents has emerged as a promising strategy for treating various diseases.

Mitogen-Activated Protein Kinase 3 (MAPK3), also known as extracellular signal-regulated kinase 1 (ERK1), is a serine/threonine protein kinase that plays a crucial role in intracellular signal transduction pathways. It is involved in the regulation of various cellular processes, including proliferation, differentiation, and survival, in response to extracellular stimuli such as growth factors, hormones, and stress.

MAPK3 is activated through a phosphorylation cascade that involves the activation of upstream MAPK kinases (MKK or MEK). Once activated, MAPK3 can phosphorylate and activate various downstream targets, including transcription factors, to regulate gene expression. Dysregulation of MAPK3 signaling has been implicated in several diseases, including cancer and neurological disorders.

Cyclic adenosine monophosphate (cAMP) is a key secondary messenger in many biological processes, including the regulation of metabolism, gene expression, and cellular excitability. It is synthesized from adenosine triphosphate (ATP) by the enzyme adenylyl cyclase and is degraded by the enzyme phosphodiesterase.

In the body, cAMP plays a crucial role in mediating the effects of hormones and neurotransmitters on target cells. For example, when a hormone binds to its receptor on the surface of a cell, it can activate a G protein, which in turn activates adenylyl cyclase to produce cAMP. The increased levels of cAMP then activate various effector proteins, such as protein kinases, which go on to regulate various cellular processes.

Overall, the regulation of cAMP levels is critical for maintaining proper cellular function and homeostasis, and abnormalities in cAMP signaling have been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Deoxycytidine kinase (dCK) is an enzyme that plays a crucial role in the phosphorylation of deoxycytidine and its analogs, which are important components in the intracellular metabolism of DNA precursors. The enzyme catalyzes the transfer of a phosphate group from adenosine triphosphate (ATP) to the hydroxyl group at the 5' carbon atom of deoxycytidine, forming deoxycytidine monophosphate (dCMP).

Deoxycytidine kinase is a key enzyme in the salvage pathway of pyrimidine nucleotide synthesis and is also involved in the activation of many antiviral and anticancer drugs that are analogs of deoxycytidine. The activity of dCK is tightly regulated, and its expression levels can vary depending on the cell type and physiological conditions.

In addition to its role in nucleotide metabolism, dCK has been implicated in various biological processes, including DNA damage response, cell cycle regulation, and apoptosis. Abnormalities in dCK activity or expression have been associated with several human diseases, including cancer and viral infections. Therefore, modulation of dCK activity has emerged as a potential therapeutic strategy for the treatment of these conditions.

Creatine kinase (CK) is a muscle enzyme that is normally present in small amounts in the blood. It is primarily found in tissues that require a lot of energy, such as the heart, brain, and skeletal muscles. When these tissues are damaged or injured, CK is released into the bloodstream, causing the levels to rise.

Creatine kinase exists in several forms, known as isoenzymes, which can be measured in the blood to help identify the location of tissue damage. The three main isoenzymes are:

1. CK-MM: Found primarily in skeletal muscle
2. CK-MB: Found primarily in heart muscle
3. CK-BB: Found primarily in the brain

Elevated levels of creatine kinase, particularly CK-MB, can indicate damage to the heart muscle, such as occurs with a heart attack. Similarly, elevated levels of CK-BB may suggest brain injury or disease. Overall, measuring creatine kinase levels is a useful diagnostic tool for assessing tissue damage and determining the severity of injuries or illnesses.

Protein-Tyrosine Kinases (PTKs) are a type of enzyme that plays a crucial role in various cellular functions, including signal transduction, cell growth, differentiation, and metabolism. They catalyze the transfer of a phosphate group from ATP to the tyrosine residues of proteins, thereby modifying their activity, localization, or interaction with other molecules.

PTKs can be divided into two main categories: receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (NRTKs). RTKs are transmembrane proteins that become activated upon binding to specific ligands, such as growth factors or hormones. NRTKs, on the other hand, are intracellular enzymes that can be activated by various signals, including receptor-mediated signaling and intracellular messengers.

Dysregulation of PTK activity has been implicated in several diseases, such as cancer, diabetes, and inflammatory disorders. Therefore, PTKs are important targets for drug development and therapy.

Aminoimidazole carboxamide is a compound that is involved in the metabolic pathways of nucleotide synthesis in cells. It is also known as AICA ribonucleotide, and is a precursor to an important energy molecule in the body called adenosine triphosphate (ATP).

In medical terms, aminoimidazole carboxamide is sometimes used as a research tool to study cellular metabolism and has been investigated for its potential therapeutic use in various conditions such as neurodegenerative disorders and ischemia-reperfusion injury. However, it is not commonly used as a medication in clinical practice.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

Theophylline is a medication that belongs to a class of drugs called methylxanthines. It is used in the management of respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and other conditions that cause narrowing of the airways in the lungs.

Theophylline works by relaxing the smooth muscle around the airways, which helps to open them up and make breathing easier. It also acts as a bronchodilator, increasing the flow of air into and out of the lungs. Additionally, theophylline has anti-inflammatory effects that can help reduce swelling in the airways and relieve symptoms such as coughing, wheezing, and shortness of breath.

Theophylline is available in various forms, including tablets, capsules, and liquid solutions. It is important to take this medication exactly as prescribed by a healthcare provider, as the dosage may vary depending on individual factors such as age, weight, and liver function. Regular monitoring of blood levels of theophylline is also necessary to ensure safe and effective use of the medication.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

MAP (Mitogen-Activated Protein) Kinase Kinase Kinases (MAP3K or MAPKKK) are a group of protein kinases that play a crucial role in intracellular signal transduction pathways, which regulate various cellular processes such as proliferation, differentiation, survival, and apoptosis. They are called "kinases" because they catalyze the transfer of a phosphate group from ATP to specific serine or threonine residues on their target proteins.

MAP3Ks function upstream of MAP Kinase Kinases (MKKs or MAP2K) and MAP Kinases (MPKs or MAPK) in the MAP kinase cascade. Upon activation by various extracellular signals, such as growth factors, cytokines, stress, and hormones, MAP3Ks phosphorylate and activate MKKs, which subsequently phosphorylate and activate MPKs. Activated MPKs then regulate the activity of downstream transcription factors and other target proteins to elicit appropriate cellular responses.

There are several subfamilies of MAP3Ks, including ASK, DLK, TAK, MEKK, MLK, and ZAK, among others. Each subfamily has distinct structural features and functions in different signaling pathways. Dysregulation of MAP kinase cascades, including MAP3Ks, has been implicated in various human diseases, such as cancer, inflammation, and neurodegenerative disorders.

CDC2 protein kinase, also known as cell division cycle 2 or CDK1, is a type of enzyme that plays a crucial role in the regulation of the cell cycle. The cell cycle is the series of events that cells undergo as they grow, replicate their DNA, and divide into two daughter cells.

CDC2 protein kinase is a member of the cyclin-dependent kinase (CDK) family, which are serine/threonine protein kinases that are activated by binding to regulatory subunits called cyclins. CDC2 protein kinase is primarily associated with the regulation of the G2 phase and the entry into mitosis, the stage of the cell cycle where nuclear and cytoplasmic division occur.

CDC2 protein kinase functions by phosphorylating various target proteins, which alters their activity and contributes to the coordination of the different events that occur during the cell cycle. The activity of CDC2 protein kinase is tightly regulated through a variety of mechanisms, including phosphorylation and dephosphorylation, as well as the binding and destruction of cyclin subunits.

Dysregulation of CDC2 protein kinase has been implicated in various human diseases, including cancer, where uncontrolled cell division can lead to the formation of tumors. Therefore, understanding the regulation and function of CDC2 protein kinase is an important area of research in molecular biology and medicine.

Cyclin-dependent kinases (CDKs) are a family of serine/threonine protein kinases that play crucial roles in regulating the cell cycle, transcription, and other cellular processes. They are activated by binding to cyclin proteins, which accumulate and degrade at specific stages of the cell cycle. The activation of CDKs leads to phosphorylation of various downstream target proteins, resulting in the promotion or inhibition of different cell cycle events. Dysregulation of CDKs has been implicated in several human diseases, including cancer, and they are considered important targets for drug development.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Adenosine A3 receptor antagonists are a class of pharmaceutical compounds that block the action of adenosine at the A3 receptor. Adenosine is a naturally occurring purine nucleoside that acts as a neurotransmitter and modulator of various physiological processes, including cardiovascular function, immune response, and neuromodulation.

The A3 receptor is one of four subtypes of adenosine receptors (A1, A2A, A2B, and A3) that are widely distributed throughout the body. The activation of A3 receptors has been implicated in a variety of pathological conditions, including inflammation, pain, ischemia-reperfusion injury, and cancer.

Adenosine A3 receptor antagonists have been investigated as potential therapeutic agents for various diseases, such as rheumatoid arthritis, chronic pain, ischemic heart disease, and cancer. These compounds work by preventing the binding of adenosine to its receptor, thereby blocking its downstream signaling pathways.

Some examples of Adenosine A3 receptor antagonists include:

* MRS1523
* MRE-2029F20
* LUF5834
* VUF5574
* OT-7962

It is important to note that while Adenosine A3 receptor antagonists have shown promise in preclinical studies, their clinical efficacy and safety profile are still being evaluated in ongoing research.

Purinergic receptors are a type of cell surface receptor that bind and respond to purines and pyrimidines, which are nucleotides and nucleosides. These receptors are involved in various physiological processes, including neurotransmission, muscle contraction, and inflammation. There are two main types of purinergic receptors: P1 receptors, which are activated by adenosine, and P2 receptors, which are activated by ATP and other nucleotides.

P2 receptors are further divided into two subtypes: P2X and P2Y. P2X receptors are ionotropic receptors that form cation channels upon activation, allowing the flow of ions such as calcium and sodium into the cell. P2Y receptors, on the other hand, are metabotropic receptors that activate G proteins upon activation, leading to the activation or inhibition of various intracellular signaling pathways.

Purinergic receptors have been found to play a role in many diseases and conditions, including neurological disorders, cardiovascular disease, and cancer. They are also being studied as potential targets for drug development.

Pyrimidines are heterocyclic aromatic organic compounds similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring. They are one of the two types of nucleobases found in nucleic acids, the other being purines. The pyrimidine bases include cytosine (C) and thymine (T) in DNA, and uracil (U) in RNA, which pair with guanine (G) and adenine (A), respectively, through hydrogen bonding to form the double helix structure of nucleic acids. Pyrimidines are also found in many other biomolecules and have various roles in cellular metabolism and genetic regulation.

Pyruvate kinase is an enzyme that plays a crucial role in the final step of glycolysis, a process by which glucose is broken down to produce energy in the form of ATP (adenosine triphosphate). Specifically, pyruvate kinase catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), resulting in the formation of pyruvate and ATP.

There are several isoforms of pyruvate kinase found in different tissues, including the liver, muscle, and brain. The type found in red blood cells is known as PK-RBC or PK-M2. Deficiencies in pyruvate kinase can lead to a genetic disorder called pyruvate kinase deficiency, which can result in hemolytic anemia due to the premature destruction of red blood cells.

eIF-2 kinase is a type of protein kinase that phosphorylates the alpha subunit of eukaryotic initiation factor-2 (eIF-2) at serine 51. This phosphorylation event inhibits the guanine nucleotide exchange factor eIF-2B, thereby preventing the recycling of eIF-2 and reducing global protein synthesis.

There are four main subtypes of eIF-2 kinases:

1. HRI (heme-regulated inhibitor) - responds to heme deficiency and oxidative stress
2. PERK (PKR-like endoplasmic reticulum kinase) - activated by ER stress and misfolded proteins in the ER
3. GCN2 (general control non-derepressible 2) - responds to amino acid starvation
4. PKR (double-stranded RNA-activated protein kinase) - activated by double-stranded RNA during viral infections

These eIF-2 kinases play crucial roles in regulating cellular responses to various stress conditions, such as the integrated stress response (ISR), which helps maintain cellular homeostasis and promote survival under adverse conditions.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Casein kinases are a family of protein kinases that play important roles in various cellular processes, including signal transduction, cell cycle regulation, and DNA damage repair. These enzymes phosphorylate serine and threonine residues on their target proteins by transferring a phosphate group from ATP to the hydroxyl side chain of these amino acids.

There are several isoforms of casein kinases, including Casein Kinase 1 (CK1) and Casein Kinase 2 (CK2), which differ in their structure, substrate specificity, and cellular functions. CK1 is involved in various signaling pathways, such as the Wnt signaling pathway, and regulates processes such as gene transcription, DNA repair, and circadian rhythm. CK2, on the other hand, is a highly conserved serine/threonine protein kinase that plays a role in many cellular processes, including cell division, apoptosis, and transcriptional regulation.

Dysregulation of casein kinases has been implicated in various diseases, including cancer, neurodegenerative disorders, and cardiovascular disease. Therefore, these enzymes are considered important targets for the development of new therapeutic strategies.

Casein Kinase II (CK2) is a serine/threonine protein kinase that is widely expressed in eukaryotic cells and is involved in the regulation of various cellular processes. It is a heterotetrameric enzyme, consisting of two catalytic subunits (alpha and alpha') and two regulatory subunits (beta).

CK2 phosphorylates a wide range of substrates, including transcription factors, signaling proteins, and other kinases. It is known to play roles in cell cycle regulation, apoptosis, DNA damage response, and protein stability, among others. CK2 activity is often found to be elevated in various types of cancer, making it a potential target for cancer therapy.

I'm sorry for any confusion, but "Morpholines" is not a medical term. It is a chemical term that refers to a class of heterocyclic organic compounds containing one nitrogen atom and one oxygen atom in the ring. They are widely used as intermediates in the synthesis of various pharmaceuticals, agrochemicals, and dyes. If you have any questions about a medical issue or term, I'd be happy to try to help answer those for you!

Adenosine Triphosphate (ATP) is a high-energy molecule that stores and transports energy within cells. It is the main source of energy for most cellular processes, including muscle contraction, nerve impulse transmission, and protein synthesis. ATP is composed of a base (adenine), a sugar (ribose), and three phosphate groups. The bonds between these phosphate groups contain a significant amount of energy, which can be released when the bond between the second and third phosphate group is broken, resulting in the formation of adenosine diphosphate (ADP) and inorganic phosphate. This process is known as hydrolysis and can be catalyzed by various enzymes to drive a wide range of cellular functions. ATP can also be regenerated from ADP through various metabolic pathways, such as oxidative phosphorylation or substrate-level phosphorylation, allowing for the continuous supply of energy to cells.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

Ribosomal Protein S6 Kinases (RSKs) are a family of serine/threonine protein kinases that play a crucial role in the regulation of cell growth, proliferation, and survival. They are so named because they phosphorylate and regulate the function of the ribosomal protein S6, which is a component of the 40S ribosomal subunit involved in protein synthesis.

RSKs are activated by various signals, including growth factors, hormones, and mitogens, through a cascade of phosphorylation events involving several upstream kinases such as MAPK/ERK kinase (MEK) and extracellular signal-regulated kinase (ERK). Once activated, RSKs phosphorylate a wide range of downstream targets, including transcription factors, regulators of translation, and cytoskeletal proteins, thereby modulating their activities and functions.

There are four isoforms of RSKs in humans, namely RSK1, RSK2, RSK3, and RSK4, which share a common structural organization and functional domains, including an N-terminal kinase domain, a C-terminal kinase domain, and a linker region that contains several regulatory motifs. Dysregulation of RSKs has been implicated in various pathological conditions, including cancer, cardiovascular diseases, neurological disorders, and diabetes, making them attractive targets for therapeutic intervention.

Ribonucleotides are organic compounds that consist of a ribose sugar, a phosphate group, and a nitrogenous base. They are the building blocks of RNA (ribonucleic acid), one of the essential molecules in all living organisms. The nitrogenous bases found in ribonucleotides include adenine, uracil, guanine, and cytosine. These molecules play crucial roles in various biological processes, such as protein synthesis, gene expression, and cellular energy production. Ribonucleotides can also be involved in cell signaling pathways and serve as important cofactors for enzymatic reactions.

... (AdK; EC 2.7.1.20) is an enzyme that catalyzes the transfer of gamma-phosphate from Adenosine triphosphate ( ... Gupta RS (June 1996). "Adenosine-AMP exchange activity is an integral part of the mammalian adenosine kinase". Biochemistry and ... Arch JR, Newsholme EA (September 1978). "Activities and some properties of 5'-nucleotidase, adenosine kinase and adenosine ... Newby AC (February 1985). "The role of adenosine kinase in regulating adenosine concentration". The Biochemical Journal. 226 (1 ...
... adenosine 5'-phosphosulfate kinase, adenosine phosphosulfate kinase, adenosine phosphosulfokinase, adenosine-5'-phosphosulfate- ... MacRae IJ, Rose AB, Segel IH (October 1998). "Adenosine 5'-phosphosulfate kinase from Penicillium chrysogenum. site-directed ... Other names in common use include adenylylsulfate kinase (phosphorylating), 5'-phosphoadenosine sulfate kinase, ... In enzymology, an adenylyl-sulfate kinase (EC 2.7.1.25) is an enzyme that catalyzes the chemical reaction ATP + adenylyl ...
The increase in adenosine kinase results in an increased metabolic rate for adenosine nucleosides. Due to the decrease in these ... The most prevalent theory is that upon brain injury there is an increased expression of the adenosine kinase (ADK). ... ISBN 978-88-470-1642-2. Boison D (December 2006). "Adenosine kinase, epilepsy and stroke: mechanisms and therapies". Trends in ... the effects can be counteracted and moderated by adenosine. Based on the properties afforded by adenosine in preventing ...
Other members of this family (also known as the RK family) include adenosine kinase (AK), inosine-guanosine kinase, ... Maj MC, Singh B, Gupta RS (March 2002). "Pentavalent ions dependency is a conserved property of adenosine kinase from diverse ... Park J, Gupta RS (September 2008). "Adenosine kinase and ribokinase--the RK family of proteins". Cellular and Molecular Life ... "Cloning of human adenosine kinase cDNA: sequence similarity to microbial ribokinases and fructokinases". Proceedings of the ...
... adenosine kinase (AK), inosine kinase, and 1-phosphofructokinase. The members of the PfkB/RK family are identified by the ... Maj MC, Singh B, Gupta RS (March 2002). "Pentavalent ions dependency is a conserved property of adenosine kinase from diverse ... Park J, Gupta RS (September 2008). "Adenosine kinase and ribokinase--the RK family of proteins". Cellular and Molecular Life ... "Cloning of human adenosine kinase cDNA: sequence similarity to microbial ribokinases and fructokinases". Proceedings of the ...
Park, Jae; Gupta, Radhey S. (2008). "Adenosine kinase and ribokinase - the RK family of proteins". Cellular and Molecular Life ... Protein kinase A regulates metabolic enzymes by phosphorylation which causes a change in the cell depending on the original ... The ribonucleosides adenosine, cytidine, guanosine, and uridine are all derivatives of β-d-ribofuranose. Metabolically- ... cAMP, a secondary messenger, then goes on to activate protein kinase A, which is an enzyme that regulates cell metabolism. ...
Phosphorylation of cellobiose with adenosine 5'-triphosphate by a -glucoside kinase". J. Biol. Chem. 247 (11): 3415-9. PMID ... In enzymology, a beta-glucoside kinase (EC 2.7.1.85) is an enzyme that catalyzes the chemical reaction ATP + cellobiose ⇌ {\ ... This enzyme is also called beta-D-glucoside kinase (phosphorylating). Palmer RE, Anderson RL (1972). "Cellobiose metabolism in ...
Thoai NV, di Jeso F, Robin Y, der Terrossian E (1966). "Sur la nouvelle acide adenosine 5'-triphosphorique:guanidine ... In enzymology, an opheline kinase (EC 2.7.3.7) is an enzyme that catalyzes the chemical reaction ATP + guanidinoethyl methyl ... phosphotransferase, l'opheline kinase". Biochim. Biophys. Acta. 113: 542-550. doi:10.1016/s0926-6593(66)80012-7. Portal: ...
cAMP, cyclic adenosine monophosphate, phosphorylate messengers via protein kinase A (PKA). These signaling elements include ... Nitric oxide (NO) stimulates cGMP production and therefore the activation cGMP-dependent protein kinase (G kinase). This kinase ... In vivo phosphorylation of thromboxane by cyclic GMP-dependent protein kinase". Proceedings of the National Academy of Sciences ...
Delvalle JA, Asensio C (August 1978). "Distribution of adenosine 5'-triphosphate (ATP)-dependent hexose kinases in ... "A mammalian protein homologous to fructosamine-3-kinase is a ketosamine-3-kinase acting on psicosamines and ribulosamines but ... Ketosamine-3-kinases (KT3K) catalyse the phosphorylation of the ketosamine moiety of glycated proteins. The instability of a ... The family also includes ketosamine-3-kinases (KT3K). Ketosamines derive from a non-enzymatic reaction between a sugar and a ...
Adenosine kinase is an enzyme that in humans is encoded by the ADK gene. This gene encodes adenosine kinase, an abundant enzyme ... "Entrez Gene: ADK adenosine kinase". Human ADK genome location and ADK gene details page in the UCSC Genome Browser. Klobutcher ... Spychala J, Datta NS, Takabayashi K, Datta M, Fox IH, Gribbin T, Mitchell BS (Mar 1996). "Cloning of human adenosine kinase ... Singh B, Lin A, Wu ZC, Gupta RS (2001). "Gene structure for adenosine kinase in Chinese hamster and human: high-frequency ...
"Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase". Science. 253 (5018): ... She is known for her research on protein kinases, particularly protein kinase A. She was elected to the Institute of Medicine ... Taylor's research group has focused on the structure and function of protein kinases, particularly protein kinase A, since ... Taylor, SS; Yang, J; Wu, J; Haste, NM; Radzio-Andzelm, E; Anand, G (11 March 2004). "PKA: a portrait of protein kinase dynamics ...
"Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase". Science. 253 (5018): ... Hanks SK, Hunter T (May 1995). "Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain ... Protein kinase function has been evolutionarily conserved from Escherichia coli to Homo sapiens. Protein kinases play a role in ... The protein kinase domain is a structurally conserved protein domain containing the catalytic function of protein kinases. ...
Gaskin FS (2007). Mechanisms of adenosine monophosphate-activated protein kinase-induced preconditioning in ischemia/ ... Acadesine is an adenosine regulating agent developed by PeriCor Therapeutics and licensed to Schering-Plough in 2007 for phase ... Kim JE, Kim YW, Lee IK, Kim JY, Kang YJ, Park SY (March 2008). "AMP-activated protein kinase activation by 5-aminoimidazole-4- ... It stimulates glucose uptake and increases the activity of p38 mitogen-activated protein kinases α and β in skeletal muscle ...
Park J, Gupta RS: Adenosine kinase and ribokinase--the RK family of proteins. Cell Mol Life Sci 2008, 65: 2875-2896. Bork P, ... Maj MC, Singh B, Gupta RS: Pentavalent ions dependency is a conserved property of adenosine kinase from diverse sources: ... Sapico V, Anderson RL (1969). "D-fructose 1-phosphate kinase and D-fructose 6-phosphate kinase from Aerobacter aerogenes. A ... D-fructose-1-phosphate kinase, fructose 1-phosphate kinase, and 1-phosphofructokinase. This enzyme participates in fructose and ...
"Identification of a nucleoside analog active against adenosine kinase-expressing plasma cell malignancies". Journal of Clinical ...
... and inosine kinase (phosphorylating). This enzyme participates in purine metabolism. Park J, Gupta RS: Adenosine kinase and ... Spychala J, Datta NS, Takabayashi K, Datta M, Fox IH, Gribbin T, Mitchell BS: Cloning of human adenosine kinase cDNA: sequence ... Maj MC, Singh B, Gupta RS: Pentavalent ions dependency is a conserved property of adenosine kinase from diverse sources: ... Other members of this family (also known as the Ribokinase family) include ribokinase (RK) adenosine kinase (AK), fructokinase ...
Induction by regulatory subunit and inhibition by catalytic subunit of adenosine 3':5'-monophosphate-dependent protein kinase ... Protein kinase A catalytic subunit (PKA Cα) is a member of the AGC kinase family (protein kinases A, G, and C), and contributes ... A-kinase-anchoring proteins (AKAPs) bind a surface formed between both R subunits and target the kinase to different locations ... They realized that a key metabolic enzyme called phosphorylase kinase was activated by another kinase that was dependent on the ...
ROS and adenosine acting on kinases such as PKCε and Src, which in turn activate gene transcription and upregulation of late PC ... "Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade". Cardiovascular Research. 70 ... These signaling events act on the ROS-generating mitochondria, activate PKCε and the Reperfusion Injury Salvage Kinase (RISK) ... "Novel functional role of heat shock protein 90 in protein kinase C-mediated ischemic postconditioning". The Journal of Surgical ...
Adenylate kinase is a specific nucleoside-monophosphate kinase that functions only on adenosine-monophosphate. Carbohydrate ... The nucleoside, adenosine, is then deaminated and hydrolyzed to form hypoxanthine via adenosine deaminase and nucleosidase ... "Adenosine deaminase (ADA) deficiency". Learn.Genetics. Archived from the original on 3 November 2014. Retrieved 31 October 2014 ... AMP and GMP can then be converted into ATP and GTP, respectively, by kinases that add additional phosphates. ATP stimulates ...
Krishan S, Richardson DR, Sahni S (March 2015). "Adenosine monophosphate-activated kinase and its key role in catabolism: ... The eukaryotic cell enzyme 5' adenosine monophosphate-activated protein kinase, or AMPK, utilizes AMP for homeostatic energy ... including adenosine monophosphate, are formed. AMP can be regenerated to ATP as follows: AMP + ATP → 2 ADP (adenylate kinase in ... Adenosine monophosphate (AMP), also known as 5'-adenylic acid, is a nucleotide. AMP consists of a phosphate group, the sugar ...
Yeast tRNA kinase then phosphorylates the 5'-hydroxyl group using adenosine triphosphate. Yeast tRNA cyclic phosphodiesterase ... Yeast tRNA ligase adds an adenosine monophosphate group to the 5' end of the 3'-half and joins the two halves together. NAD- ... The 2'OH of a specific adenosine in the intron attacks the 5' splice site, thereby forming the lariat The 3'OH of the 5' exon ...
Kirchberger MA, Tada M, Repke DI, Katz AM (1972). "Cyclic adenosine 3', 5'-monophosphate-dependent protein kinase stimulation ... Hicks MJ, Shigekawa M, Katz AM (1979). "Mechanism by which cyclic adenosine 3', 5'-monophosphate-dependent protein kinase ... monophosphate-dependent protein kinase". J Biol Chem. 250 (7): 2640-2647. PMID 235523. Katz AM, Repke DI, Dunnett J, Hasselbach ... "Phosphorylation of a 22,000-dalton component of the cardiac sarcoplasmic reticulum by adenosine 3', 5'- ...
... inhibits EGFR tyrosine kinase by binding to the adenosine triphosphate (ATP)-binding site of the enzyme. Thus the ... Research on gefitinib-sensitive non-small cell lung cancers has shown that a mutation in the EGFR tyrosine kinase domain is ... February 2008). "The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP". Proceedings of ... These mutations tend to confer increased sensitivity to tyrosine kinase inhibitors such as gefitinib and erlotinib. Of the ...
5' adenosine-monophosphate-activated protein kinase (AMPK) has also been found to be an effector for RHEB. AMPK is a protein ... Yee WM, Worley PF (Feb 1997). "Rheb interacts with Raf-1 kinase and may function to integrate growth factor- and protein kinase ... AMP-activated protein kinase (AMPK) RAF proto-oncogene serine/threonine-protein kinase (C-Raf) mammalian Target of Rapamycin ... Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J (Apr 2005). "Rheb binds and regulates the mTOR kinase". Current Biology. 15 ( ...
... kinetic properties of the adenosine triphosphate sulfurylase and adenosine 5'-phosphosulfate kinase domains". Biochemistry. 43 ... Sekulic N, Konrad M, Lavie A (2007). "Structural mechanism for substrate inhibition of the adenosine 5'-phosphosulfate kinase ... In humans, PAPS is synthesized from adenosine 5-prime triphosphate (ATP) and inorganic sulfate by 2 isoforms, PAPSS1 and PAPSS2 ... 1998). "cDNA cloning, expression, and characterization of the human bifunctional ATP sulfurylase/adenosine 5'-phosphosulfate ...
This protein is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase (PKA) in cardiac muscle. In ... "The stimulation of calcium transport in cardiac sarcoplasmic reticulum by adenosine 3':5'-monophosphate-dependent protein ... kinase". The Journal of Biological Chemistry. 249 (19): 6174-80. doi:10.1016/S0021-9258(19)42237-0. PMID 4371608. Asahi M, ...
Metabolism of PEP to pyruvic acid by pyruvate kinase (PK) generates adenosine triphosphate (ATP) via substrate-level ...
"Genomic organization of the mouse and human genes encoding the ATP sulfurylase/adenosine 5'-phosphosulfate kinase isoform SK2 ...
Metabolism of PEP to pyruvic acid by pyruvate kinase (PK) generates adenosine triphosphate (ATP) via substrate-level ...
Adenosine kinase (AdK; EC 2.7.1.20) is an enzyme that catalyzes the transfer of gamma-phosphate from Adenosine triphosphate ( ... Gupta RS (June 1996). "Adenosine-AMP exchange activity is an integral part of the mammalian adenosine kinase". Biochemistry and ... Arch JR, Newsholme EA (September 1978). "Activities and some properties of 5-nucleotidase, adenosine kinase and adenosine ... Newby AC (February 1985). "The role of adenosine kinase in regulating adenosine concentration". The Biochemical Journal. 226 (1 ...
F. M. Red OLaughlin, III, is a researcher, author, and public speaker. He speaks on health and wellness, aging, personal growth, and motivation. Red states often that, "If you treat symptoms, you will always treat symptoms. You must treat the cause of a problem to correct it." I research what happens at the cellular level in the human body, biochemically speaking. I look for cause and effect relationships. I identify the causes of health problems. I write and speak about those causes and the potential options for correcting those problems.. ...
Additional Adenosine A2B receptor (A2BR) Inhibitor Source evaluation of naturally genetic variations in TaCYP78A5-2A identified ...
While removing adenosine in the purine salvage pathway, adenosine kinase (ADK) regulates methylation reactions. We aimed to ... Hepatocyte Adenosine Kinase Promotes Excessive Fat Deposition and Liver Inflammation.. Li, Honggui; Zheng, Juan; Xu, Qian; Yang ...
p53 activates adenosine monophosphate activated protein kinase (AMPK), a major upstream negative regulator of mTOR, and induces ... Phosphorylation and activation of heart 6-phosphofructo-2-kinase by protein kinase B and other protein kinases of the insulin ... Adenosine monophosphate activated protein kinase (AMPK) is a metabolic sensor that helps maintain cellular energy homeostasis [ ... AMPK, adenosine monophosphate activated protein kinase; MUC16, mucin 16; mTOR, mammalian target of rapamycin; RTKs, receptor ...
9] changes in the enzyme adenosine monophosphate-activated protein kinase activity, [10] and modulation of activator protein 1 ... AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushings syndrome. FASEB ...
cAMP-dependent protein kinase regulates inhibition of adenosine transport by ethanol. L E Nagy, I Diamond and A S Gordon ... Distinct pathways of desensitization of A1- and A2-adenosine receptors in DDT1 MF-2 cells. V Ramkumar, M E Olah, K A Jacobson ... Structure-activity relationships of phenothiazines and related drugs for inhibition of protein kinase C. D T Aftab, L M Ballas ... SB-431542 Is a Potent and Specific Inhibitor of Transforming Growth Factor-β Superfamily Type I Activin Receptor-Like Kinase ( ...
Impaired adenosine monophosphate-activated protein kinase signalling in dorsal root ganglia neurons is linked to mitochondrial ... Yerra VG, Kumar A. Adenosine monophosphate-activated protein kinase abates hyperglycaemia-induced neuronal injury in ... ULK1 induces autophagy by phosphorylating beclin-1 and activating VPS34 lipid kinase. Nat Cell Biol (2013) 15:741-50. doi: ... Huang DY, Gao H, Boini KM, Osswald H, Nürnberg B, Lang F. In vivo Stimulation of AMP-activated protein kinase enhanced ...
2007) Adenosine receptor A2A-R contributes to motoneuron survival by transactivating the tyrosine kinase receptor TrkB. Proc ... In previous studies on mAChR drugs (Santafé et al., 2003), protein kinase C drugs (Santafé et al., 2005), and protein kinase A ... 2006) Muscarinic autoreceptors modulate transmitter release through protein kinase C and protein kinase A in the rat motor ... 2000) Adenosine receptor expression and modulation of Ca(2+) channels in rat striatal cholinergic interneurons. J Neurophysiol ...
... problems arise because patients with RA can no longer activate the adenosine monophosphate-activated protein kinase enzyme. It ... the cellular power sources in patients with RA cannot provide as much energy in the form of adenosine triphosphate as in ...
... the mechanism by which metformin may reduce tumor growth.³ Metformin activates adenosine-monophosphate activated protein kinase ...
Debio 0123 is an investigational, orally bioavailable, highly selective, adenosine triphosphate (ATP)-competitive inhibitor of ... the WEE1 tyrosine kinase. WEE1 is a key regulator of cell cycle progression that influences entry into mitosis by modulating ... activity of cyclin-dependent kinase 1 (CDK1, also referred to as cell division cycle 2 [CDC2]). Inhibition of WEE1 presents an ...
Mutations in regulatory subunit type 1A of cyclic adenosine 5-monophosphate-dependent protein kinase (PRKAR1A): phenotype ... The lack of this subunit causes protein kinase A to be turned on more often than normal, which leads to uncontrolled cell ... This gene provides instructions for making one part (subunit) of an enzyme called protein kinase A, which promotes cell growth ... Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A): an update. Hum ...
... is governed in part by the nitric oxide regulation of cyclic guanosine and adenosine monophosphate-dependent protein kinases ( ...
We identify EspJ as a unique adenosine diphosphate (ADP) ribosyltransferase that directly inhibits Src kinase by simultaneous ... The Escherichia coli effector EspJ blocks Src kinase activity via amidation and ADP ribosylation. , Nature Communications, Vol ... Instead, Netrin-1 selectively triggers phosphorylation of mammalian Robo3 via Src kinases. Robo3 does not bind Netrin-1 ... which are generated following phosphorylation of the bacterial effector Tir by cellular Src and Abl family tyrosine kinases. ...
Extracellular Signal-Regulated MAP Kinases / metabolism * Gene Expression Regulation / physiology* * Humans * ... The neuronal Ca(2+) -binding protein 2 (NECAB2) interacts with the adenosine A(2A) receptor and modulates the cell surface ... was identified as a binding partner for the adenosine A(2A) receptor (A(2A)R) interacting with its C-terminal domain. Co- ...
ADENOSINE-KINASE-INHIBITORS * ANTIBIOTICS TUBERCIDIN * ANTIVIRAL ACTIVITY * Chemistry, Medicinal * DERIVATIVES * DIMROTH- ... Synthesis of Purine and 7-Deazapurine Nucleoside Analogues of 6-N-(4-Nitrobenzyl)adenosine; Inhibition of Nucleoside Transport ... 2014). Synthesis of Purine and 7-Deazapurine Nucleoside Analogues of 6-N-(4-Nitrobenzyl)adenosine; Inhibition of Nucleoside ... 2014). Synthesis of Purine and 7-Deazapurine Nucleoside Analogues of 6-N-(4-Nitrobenzyl)adenosine; Inhibition of Nucleoside ...
The adenosine 3,5-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) is localized through interaction of the ... The crystal structure of the SAM domain from an Eph receptor tyrosine kinase, EphB2, reveals two large interfaces. In one ... Solution structure of the N-terminal SAM-domain of human KIAA0902 protein (connector enhancer of kinase suppressor of ras 2). ... Among these are over 40 EPH-related receptor tyrosine kinases (RPTK), Drosophila bicaudal-C, a p53 from Loligo forbesi, and ...
Phosphorylase b kinase exists in an inactive form that is activated by the cyclic adenosine monophosphate (cAMP)-dependent ... Hepatic phosphorylase deficiency or deficiency of other enzymes (eg, adenylate cyclase, protein kinase A, phosphorylase kinase ... whereas other authors label phosphorylase b kinase deficiency as GSD type IX and cAMP-dependent protein kinase deficiency as ... The X-linked form of hepatic phosphorylase kinase deficiency is the most common (75%) among patients with GSD type VI. The gene ...
CBS_euAMPK_gamma-like_repeat2; CBS pair domain found in 5-AMP (adenosine monophosphate)-activated protein kinase. ... CBS_euAMPK_gamma-like_repeat2; CBS pair domain found in 5-AMP (adenosine monophosphate)-activated protein kinase. ... CBS_euAMPK_gamma-like_repeat2; CBS pair domain found in 5-AMP (adenosine monophosphate)-activated protein kinase. ... CBS_euAMPK_gamma-like_repeat2; CBS pair domain found in 5-AMP (adenosine monophosphate)-activated protein kinase. ...
ADAR, RNA-specific adenosine deaminase; IRF, IFN-regulatory factor; JAK, Janus kinase; Mx, myxovirus-resistance proteins; OAS, ... Yeh, T. The Janus kinase family of protein tyrosine kinases and their role in signaling. Meraz, M. Targeted disruption of the ... Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation. This ... ADAR is involved in RNA editing by virtue of its ability to deaminate adenosine to yield inosine, which provides a mechanism to ...
... the serine/threonine kinase adenosine monophosphate (AMP)-activated protein kinase (AMPK), to sense low cellular adenosine ... Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab ... that activates adenosine monophosphate-activated protein kinase (AMPK). ATP, adenosine triphosphate; ADP, adenosine diphosphate ... liver kinase B 1; CAMKK2, calcium/calmodulin-dependent protein kinase kinase; PDK1, pyruvate dehydrogenase kinase 1; CRAC, ...
Creatine phosphate and adenosine diphosphate (ADP) are acted upon by CK in the serum specimen. Creatine and ATP are produced ... The method to measure creatine phosphokinase (CPK) or creatine kinase (CK) utilizes a coupled enzyme reaction. ...
5´-Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a highly conserved serine/threonine kinase that serves as a ... such as liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) [14]. Moreover, both AMP and ADP ... Ca2+/calmodulin-dependent protein kinase kinase is involved in AMP-activated protein kinase activation by alpha-lipoic acid in ... 5´-Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a cellular energy sensor, is an essential enzyme that helps ...
Herein, we summarize emerging agents including tyrosine kinase inhibitors, checkpoint inhibitors, and other potential ... Tyrosine kinase inhibitors and immunotherapy for lung cancer are the two major areas undergoing rapid development. Although ... Dabrafenib was a highly potent adenosine triphosphate-competitive inhibitor of BRAF kinase selective for the BRAF V600E ... Anaplastic lymphoma kinase and ROS1 proto-oncogene receptor kinase inhibitors. Ceritinib. The current standard first-line ...
... behind berberines glucose balancing mechanisms include activation of a protein called adenosine mono-phosphate kinase (AMPK). ... AMP KINASE. ↓ Body Weight. ↑ Fatty Acids. Oxidation. + Supports Healthy Cholesterol and Triglyceride Levels. ↑ Glucose ...
Mechanisms of protein kinase C signaling in the modulation of 3,5-cyclic adenosine monophosphate-mediated steroidogenesis in ... Intermediate role of adenosine 3:5-cyclic monophosphate and protein kinase during gonadotropin-induced steroidogenesis in ... Regulation of Leydig cell steroidogenesis by extracellular signal-regulated kinase 1/2: role of protein kinase A and protein ... resulting in intracellular cyclic adenosine-monophosphate (cAMP) increase, in downstream activation of the protein kinase A ( ...
2] changes in the enzyme adenosine monophosphate-activated protein kinase activity, [3] and modulation of activator protein 1 ( ... AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushings syndrome. FASEB ...
  • EC 2.7.1.20) is an enzyme that catalyzes the transfer of gamma-phosphate from Adenosine triphosphate (ATP) to adenosine (Ado) leading to formation of Adenosine monophosphate (AMP). (wikipedia.org)
  • Structural and biochemical data revealed that binding of phosphorylated p27 (phosp27) to CDK4 altered the kinase adenosine triphosphate site to promote phosphorylation of the retinoblastoma tumor suppressor protein (Rb) and other substrates. (rcsb.org)
  • Small molecule tyrosine kinase inhibitors, such as gefitinib and erlotinib, selectively bind the adenosine triphosphate (ATP)-binding site of the EGFR tyrosine kinase receptor, inhibiting the receptor's intracellular domain via preventing phosphorylation. (medscape.com)
  • Thus, citric acid cycle intermedi- ates are not used for adenosine triphosphate (ATP) production and are shuttled out of the mitochondria, providing precursors for nucleotide, amino acid, and lipid synthesis path- ways for the dividing cell [13]. (who.int)
  • Berberine activates adenosine monophosphate kinase (AMPK). (acuatlanta.net)
  • One important factor involved in the food intake and inflammation is adenosine monophosphate-dependent kinase (AMPK), a serine/threonine kinase activated by phosphorylation. (frontiersin.org)
  • AMPK, an evolutionary conserved serine/threonine kinase, is a heterotrimeric complex formed by a catalytic α subunit and regulatory β and γ subunits. (frontiersin.org)
  • AMP-activated protein kinase (AMPK) is a serine/threonine kinase sensitive to cellular energy challenges. (hindawi.com)
  • In rare diseases, development of PXL770 , a first-in-class direct adenosine monophosphate-activated protein kinase (AMPK) activator, is focused on the treatment of adrenoleukodystrophy (ALD) and autosomal dominant polycystic kidney disease (ADPKD). (biospace.com)
  • This is mediated via alterations in the levels and activities of the cellular nutrient sensors 5′ adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1), intracellular accumulation of metabolic intermediates such as succinate and citrate, and increases in free fatty acids (FFAs) and hyperglycaemia-induced advanced glycation end-products (AGEs) that bind to receptors on the macrophage surface. (biomedcentral.com)
  • Applications related to adenosine monophosphate-activated protein kinase (AMPK) activation and berberine's possible therapeutic use in metabolic syndrome, type 2 diabetes, and dyslipdemia are reviewed in this article. (naturalmedicinejournal.com)
  • The treament downregulated genes mediating hypoxia-inducible factor (HIF)-1a stability, metabolism and survival, activated adenosine monophosphate-activated protein kinase (AMPK) and inhibited mTOR, a critical activator of HIF-1a signaling. (nih.gov)
  • By targeting electron transport chain complex 1 and independently of AMP-activated protein kinase (AMPK) or NF-κB, metformin blocked LPS-induced and ATP-dependent mitochondrial (mt) DNA synthesis and generation of oxidized mtDNA, an NLRP3 ligand. (lu.se)
  • This effect is governed in part by the nitric oxide regulation of cyclic guanosine and adenosine monophosphate-dependent protein kinases (PKG and PKA) and is not fully understood. (cdc.gov)
  • The specificity of the K-252a blocking effect on trkB was confirmed with the anti-trkB antibody 47/trkB, which reduces evoked ACh release, like K-252a, whereas the nonpermeant tyrosine kinase blocker K-252b does not. (jneurosci.org)
  • through specific tyrosine kinase (trk) receptors (and one unspecific receptor, p75 NTR ). (jneurosci.org)
  • There are several different types of EGFRIs, including small molecule tyrosine kinase inhibitors, monoclonal antibodies, and multikinase inhibitors. (medscape.com)
  • Diagnosis of adenosine deaminase deficiency is by DNA analysis. (msdmanuals.com)
  • Treatment of adenosine deaminase deficiency is by bone marrow or stem cell transplantation and enzyme replacement therapy. (msdmanuals.com)
  • Our data characterize phosp27-CDK4-CycD1 as an active Rb kinase that is refractory to clinically relevant CDK4/6 inhibitors. (rcsb.org)
  • This gene provides instructions for making one part (subunit) of an enzyme called protein kinase A, which promotes cell growth and division (proliferation). (medlineplus.gov)
  • The A2b receptor (A2bR) is one of the adenosine receptor family. (biospraysehatalami.com)
  • Launch Adenosine continues to be described as a significant regulator of immune system response within the tumor microenvironment [1 2 The immune-suppressive ramifications of adenosine in tumors are reliant on the A2a receptor subtype (A2aR) which inhibits T cell features favoring tumor advancement [3]. (biospraysehatalami.com)
  • On the other hand arousal of A3 adenosine receptor (A3R) subtype can markedly limit tumor development by promoting a competent antitumor immune system response in mice [4 5 There's growing evidence which the A2b receptor subtype (A2bR) may also impact tumor progression in a few murine tumor versions. (biospraysehatalami.com)
  • MDSCs donate to tumor immune system tolerance by launching adenosine within a Compact disc73-reliant way [10 11 Furthermore A2bR blockade can decrease the development of bladder and breasts malignancies in mice by marketing a T cell-mediated response within a chemokine C-X-C receptor 3 (CXCR3)-reliant way [12]. (biospraysehatalami.com)
  • AHL downregulated proliferator‑activated receptor γ, CCAAT enhancer binding protein α and perilipin‑1 levels, while upregulating adipose triglyceride lipase, phosphorylated (p‑)hormone‑sensitive lipase, p‑adenosine monophosphate activated protein kinase, uncoupling protein 1, peroxisome‑proliferator‑activated receptor‑γ coactivator‑1 α and PR domain containing 16 levels in 3T3‑L1 cells. (spandidos-publications.com)
  • ADA degrades toxic adenosine and deoxyadenosine, which accumulate in the cells of patients. (lu.se)
  • Adenosine deaminase converts adenosine and deoxyadenosine to inosine and deoxyinosine, which are further broken down and excreted. (msdmanuals.com)
  • Distinct pathways of desensitization of A1- and A2-adenosine receptors in DDT1 MF-2 cells. (aspetjournals.org)
  • The neurotrophin brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4) and the receptors tropomyosin-related kinase B (trkB) and p75 NTR are present in the nerve terminals on the neuromuscular junctions (NMJs) of the levator auris longus muscle of the adult mouse. (jneurosci.org)
  • These metabotropic receptors are coupled to various intracellular pathways, although they can share several signaling links from the limited repertoire of presynaptic effector kinases, target ionic channels, and other molecules of the release machinery. (jneurosci.org)
  • Hepatocyte Adenosine Kinase Promotes Excessive Fat Deposition and Liver Inflammation. (bvsalud.org)
  • 60 known mutations) results in accumulation of adenosine, which is converted to its ribonucleotide and deoxyribonucleotide (dATP) forms by cellular kinases. (msdmanuals.com)
  • Extracellular ATP has been shown to activate protein kinase C (PKC) after binding to a purinoceptor. (tmu.edu.tw)
  • A2bR is normally turned on by high degrees of adenosine [6] attained in hypoxic tumor microenvironments [1]. (biospraysehatalami.com)
  • This was because of an impact on adenosine-mediated discharge of angiogenic elements such as for example vascular endothelial development factor from web host immune system cells [7]. (biospraysehatalami.com)
  • Adenosine 5'monophosphate-activated protein kinase activation reduces the risks of psoriasis and its comorbidities: a mendelian randomisation study in the UK Biobank. (cdc.gov)
  • The p27 protein is a canonical negative regulator of cell proliferation and acts primarily by inhibiting cyclin-dependent kinases (CDKs). (rcsb.org)
  • The lack of this subunit causes protein kinase A to be turned on more often than normal, which leads to uncontrolled cell proliferation. (medlineplus.gov)
  • It belongs to the phosphofructokinase B (PfkB) family of sugar kinases. (wikipedia.org)
  • Other members of this family (also known as the RK family) include ribokinase (RK), inosine-guanosine kinase, fructokinase, and 1-phosphofructokinase. (wikipedia.org)
  • We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). (rcsb.org)
  • By targeting electron transport chain complex 1 and independently of AMP-activated protein kinase. (lu.se)
  • Anti-hypertensive and endothelia protective effects of Fufang Qima capsule on primary hypertension via adiponectin/adenosine monophosphate activated protein kinase pathway. (bvsalud.org)
  • Adenosine monophosphate (AMP) deaminase deficiency is a condition that can affect the muscles used for movement (skeletal muscles). (nih.gov)
  • gene provides instructions for producing an enzyme called adenosine monophosphate (AMP) deaminase. (nih.gov)
  • 3. Development of novel adenosine monophosphate-activated protein kinase activators. (nih.gov)
  • 8. Metformin inhibits growth of human non-small cell lung cancer cells via liver kinase B-1-independent activation of adenosine monophosphate-activated protein kinase. (nih.gov)
  • 9. Synthesis and biological evaluation of 1,4-diaryl-2-azetidinones as specific anticancer agents: activation of adenosine monophosphate activated protein kinase and induction of apoptosis. (nih.gov)
  • Intracellular adenosine is rapidly metabolized either via phosphorylation to adenosine monophosphate by adenosine kinase, or via deamination to inosine by adenosine deaminase in the cytosol. (nih.gov)
  • Adenosine monophosphate formed by phosphorylation of adenosine is incorporated into the high-energy phosphate pool. (nih.gov)
  • Altered Store Operated Calcium Entry Increases Cyclic 3',5'-Adenosine Monophosphate Production and Extracellular Signal-Regulated Kinases 1 and 2 Phosphorylation in Polycystin-2-Defective Cholangiocytes. (nih.gov)
  • Adenylate Kinase 4 Modulates the Resistance of Breast Cancer Cells to Tamoxifen through an m6A-Based Epitranscriptomic Mechanism. (nih.gov)
  • In this study, we found that the protein levels of adenylate kinase 4 (AK4) and m6A writer METTL3 are significantly higher in tamoxifen-resistant (TamR) MCF-7 cells than in parental cells. (nih.gov)
  • Purification and Characterization of Adenylate Kinase as an Apparent Adenosine Triphosphate-dependent Inhibitor of Ribonuclease II in Escherichia coli . (nih.gov)
  • Treatment with AICAR inhibited the phosphorylation of retinoblastoma gene product (Rb) induced by PDGF-BB or FCS, and increased the expression of cyclin-dependent kinase inhibitor p21(CIP) but not that of p27(KIP). (nih.gov)
  • cyclin dependent kinase in. (gsea-msigdb.org)
  • The mutation responsible for this condition changes a single protein building block (amino acid) in the gamma-2 subunit of AMP-activated protein kinase. (medlineplus.gov)
  • These mutations change single amino acids in the gamma-2 subunit of AMP-activated protein kinase. (medlineplus.gov)
  • Adenosine kinase (AdK) inhibitors raise the level of endogenous adenosine, particularly in disease states, and are of interest for the potential treatment of seizures and neurodegenerative and inflammatory conditions. (nih.gov)
  • The multifold action of adenosine is an endogenous self-correcting system. (nih.gov)
  • Adenosine is an endogenous nucleoside occurring in all cells of the body. (nih.gov)
  • Adenosine kinase inhibitors (AKIs) represent an alternative strategy, since AKIs may raise local adenosine levels in a more site- and event-specific manner and thereby elicit the desired pharmacology with a greater therapeutic window. (medchemexpress.cn)
  • A recent study by Egan et al demonstrated that the ability of AMPK1 to successfully phosphorylate ULK1 protein kinases is essential for autophagy and cell survival following starvation. (medscape.com)
  • [ 88 ] TORC1 activation subsequently leads to phosphorylation and inhibition of ATG1, ATG13, FIP200, components of the ULK1 protein kinase complex that initiate autophagy. (medscape.com)
  • This A2AR-mediated control of neurotoxicity involved the control of Aβ1-42-induced p38 phosphorylation and was independent from cAMP/PKA (protein kinase A) pathway. (nih.gov)
  • Since adenosine kinase has a lower Km and Vmax than adenosine deaminase, deamination plays a significant role only when cytosolic adenosine saturates the phosphorylation pathway. (nih.gov)
  • Adenosine deaminase (ADA) deficiency is an inherited disorder that damages the immune system and causes severe combined immunodeficiency (SCID). (nih.gov)
  • Adenosine deaminase 2 (ADA2) deficiency is a disorder characterized by abnormal inflammation of various tissues. (nih.gov)
  • Together, these results show that A2ARs play a crucial role in the development of Aβ-induced synaptotoxicity leading to memory dysfunction through a p38 MAPK (mitogen-activated protein kinase)-dependent pathway and provide a molecular basis for the benefits of caffeine consumption in AD. (nih.gov)
  • Adenosine kinase (AK) is a cytosolic enzyme that catalyzes the conversion of adenosine to AMP. (medchemexpress.cn)
  • Adenosine is antagonized competitively by methylxanthines such as caffeine and theophylline, and potentiated by blockers of nucleoside transport such as dipyridamole. (nih.gov)
  • gene provides instructions for making an enzyme called adenosine deaminase 2. (nih.gov)
  • Hepatocyte adenosine kinase promotes excessive fat deposition and liver inflammation. (tamu.edu)
  • Commonly used substrate of motor proteins, kinases, and other ATP binding proteins. (jenabioscience.com)
  • Blocking regulatory, but not catalytic, subunits of PKA I abrogates the inhibitory effects of adenosine. (nih.gov)
  • Studies suggest that AMP-activated protein kinase may play a role in controlling the activity of other genes, although many of these genes have not been identified. (medlineplus.gov)
  • The regulation of glycolysis by lncRNA is through the direct regulation of glycolytic rate-limiting enzymes and lactate or indirect regulation of glycolytic upstream genes and kinases. (frontiersin.org)
  • Adenosine-mediated inhibition of cytotoxic activity and cytokine production by IL-2/NKp46-activated NK cells: involvement of protein kinase A isozyme I (PKA I). (nih.gov)
  • Adenosine is not chemically related to other antiarrhythmic drugs. (nih.gov)
  • Inosine formed by deamination of adenosine can leave the cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid. (nih.gov)
  • 18. Antidiabetic and antiobesity effects of Ampkinone (6f), a novel small molecule activator of AMP-activated protein kinase. (nih.gov)
  • Each mL contains 3 mg adenosine, and 9 mg sodium chloride, in Water for Injection. (nih.gov)
  • This enzyme breaks down molecules called adenosine and 2'-deoxyadenosine. (nih.gov)
  • 11. Role of AMP-activated protein kinase activators in antiproliferative multi-drug pituitary tumour therapies: effects of combined treatments with compounds affecting the mTOR-p70S6 kinase axis in cultured pituitary tumour cells. (nih.gov)
  • Adenosine acts as an important modulator of the activity of every organ in the body and is relevant to a wide range of physiological processes, from the central nervous system, to the immune system and the endocrine system. (nih.gov)
  • In the presence of atrial flutter or atrial fibrillation, a transient modest slowing of ventricular response may occur immediately following adenosine administration. (nih.gov)
  • 5. Novel synthetic baicalein derivatives caused apoptosis and activated AMP-activated protein kinase in human tumor cells. (nih.gov)
  • When larger doses are given by infusion, adenosine decreases blood pressure by decreasing peripheral resistance. (nih.gov)
  • These findings suggest that tumor-produced adenosine inhibits the activity of NK and other effector cells and thereby protects tumors from immune-mediated destruction. (nih.gov)
  • Adenosine is produced as a metabolite of ATP and is present in the medium surrounding all cells in the basal (resting) state, but its concentration outside the cell rises dramatically when stress to an organ or tissue occurs, such as ischemia, inflammation, and oxidative stress. (nih.gov)
  • Intravenously administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. (nih.gov)
  • Studies indicate that changes in AMP-activated protein kinase activity allow a complex sugar called glycogen to build up abnormally within cardiac muscle cells. (medlineplus.gov)
  • While extracellular adenosine is primarily cleared by cellular uptake with a half-life of less than 10 seconds in whole blood, excessive amounts may be deaminated by an ecto-form of adenosine deaminase. (nih.gov)
  • AMP-activated protein kinase is activated during times of cellular stress (such as low oxygen levels or muscle exercise), when ATP is broken down rapidly to produce energy. (medlineplus.gov)
  • AMP-activated protein kinase is likely involved in the development of the heart before birth, although its role in this process is unknown. (medlineplus.gov)
  • Other studies have found that altered AMP-activated protein kinase activity is related to changes in the regulation of certain ion channels in the heart. (medlineplus.gov)
  • PKA I, but not PKA II, participates in the inhibitory effects of adenosine. (nih.gov)
  • The intravenous bolus dose of 6 or 12 mg adenosine injection usually has no systemic hemodynamic effects. (nih.gov)
  • One potential adenosine regulating agent (ARA) target is adenosine kinase. (medchemexpress.cn)