Adenosine Kinase: 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.Adenosine: 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.Tubercidin: 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.Receptor, Adenosine A2A: 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.Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.Receptor, Adenosine A1: 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.Adenosine Deaminase Inhibitors: Drugs that inhibit ADENOSINE DEAMINASE activity.Inosine: 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)Receptor, Adenosine A2B: 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.Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.Receptors, Purinergic P1: 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).Receptor, Adenosine A3: 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.Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.5'-Nucleotidase: 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.Formycins: Pyrazolopyrimidine ribonucleosides isolated from Nocardia interforma. They are antineoplastic antibiotics with cytostatic properties.Ribonucleosides: Nucleosides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)Phosphotransferases: 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.Phosphatidylinositol 3-Kinases: 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.MAP Kinase Signaling System: 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.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Receptors, Adenosine A2: 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.Pentostatin: 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.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Adenosine A2 Receptor Agonists: Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.Inosine Monophosphate: Inosine 5'-Monophosphate. A purine nucleotide which has hypoxanthine as the base and one phosphate group esterified to the sugar moiety.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Deoxyadenosines: Adenosine molecules which can be substituted in any position, but are lacking one hydroxyl group in the ribose part of the molecule.Adenosine A2 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.Zeatin: An aminopurine factor in plant extracts that induces cell division. (Grant & Hackh's Chemical Dict, 5th ed)2-Chloroadenosine: 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.Xanthines: Purine bases found in body tissues and fluids and in some plants.Coformycin: A ribonucleoside antibiotic synergist and adenosine deaminase inhibitor isolated from Nocardia interforma and Streptomyces kaniharaensis. It is proposed as an antineoplastic synergist and immunosuppressant.Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-.Thioinosine: 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)Adenosine A1 Receptor Agonists: Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.Methylthioinosine: 6-(Methylthio)-9-beta-D-ribofuranosylpurine. An analog of inosine with a methylthio group replacing the hydroxyl group in the 6-position.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Calcium-Calmodulin-Dependent 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)Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway.Inorganic Chemicals: 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.Adenosylhomocysteinase: 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.Nucleoside Deaminases: Catalyze the hydrolysis of nucleosides with the elimination of ammonia.Nucleosides: Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed)Kinetics: The rate dynamics in chemical or physical systems.src-Family Kinases: 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.Hypoxanthines: Purine bases related to hypoxanthine, an intermediate product of uric acid synthesis and a breakdown product of adenine catabolism.Adenine NucleotidesS-Adenosylhomocysteine: 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions.Protein Kinase C: 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.Cyclic AMP-Dependent Protein Kinases: 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.Purinergic P1 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.Adenine: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.Purines: 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.p38 Mitogen-Activated Protein Kinases: 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.Nucleotides: 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)Leishmania donovani: 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.Mitogen-Activated Protein Kinase 1: 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Adenosine-5'-(N-ethylcarboxamide): A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.p21-Activated Kinases: 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.Toyocamycin: 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.Foreskin: The double-layered skin fold that covers the GLANS PENIS, the head of the penis.JNK Mitogen-Activated Protein Kinases: 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.Mitogen-Activated Protein Kinase Kinases: 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.Mitogen-Activated Protein Kinase 3: 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.Cyclic AMP: 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.Deoxycytidine Kinase: 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.Creatine Kinase: 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-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Aminoimidazole Carboxamide: 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, Cultured: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Theophylline: 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.Molecular Sequence Data: 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.MAP Kinase Kinase Kinases: 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).CDC2 Protein Kinase: 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.Cyclin-Dependent Kinases: 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.Mutation: 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.Adenosine A3 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.Receptors, Purinergic: 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.Pyrimidines: 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.Pyruvate Kinase: 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.eIF-2 Kinase: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Casein Kinases: 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.Casein Kinase II: 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.MorpholinesAdenosine Triphosphate: 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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Ribosomal Protein S6 Kinases: 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.Ribonucleotides: 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)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, Detlev (October 2006). "Adenosine kinase, epilepsy, and stroke: mechanisms and theory". ... the effects can be counteracted and moderated by adenosine. Based on the properties afforded by adenosine in preventing ...
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 ... Singh B, Lin A, Wu ZC, Gupta RS (2001). "Gene structure for adenosine kinase in Chinese hamster and human: high-frequency ... 1997). "Cloning and expression of the adenosine kinase gene from rat and human tissues". Biochem. Biophys. Res. Commun. 231 (3 ...
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" (PDF). Journal of the Salk Institute for ...
Cyclic adenosine monophosphate (cAMP) causes increased activation of protein kinase A (PKA). PKA is an enzyme that ...
... is an analog of adenosine that enters cardiac cells to inhibit adenosine kinase and adenosine deaminase. It enhances the rate ... "MECHANISMS OF ADENOSINE MONOPHOSPHATE-ACTIVATED PROTEIN KINASE-INDUCED PRECONDITIONING IN ISCHEMIA/REPERFUSION." Department of ... AICAR is an analog of adenosine monophosphate (AMP) that is capable of stimulating AMP-dependent protein kinase (AMPK) activity ... AICAR is able to enter the de novo synthesis pathway for adenosine synthesis to inhibit adenosine deaminase causing an increase ...
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 ...
"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 ...
Other members of this family (also known as the RK family) include adenosine kinase (AK), inosine-guanosine kinase, ... Park J, Gupta RS: Adenosine kinase and ribokinase--the RK family of proteins. Cell Mol Life Sci 2008, 65: 2875-2896. Bork P, ... 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: ...
... adenosine kinase (AK), inosine kinase, and 1-phosphofructokinase. The members of the PfkB/RK family are identified by the ... Park J, Gupta RS: Adenosine kinase and ribokinase--the RK family of proteins. Cell Mol Life Sci 2008, 65: 2875-2896. Bork P, ... 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: ...
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 ...
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. Nucleic acid RNA ... The nucleoside, adenosine, is then deaminated and hydrolyzed to form hypoxanthine via adenosine deaminase and nucleosidase ... "Adenosine deaminase (ADA) deficiency". Learn.Genetics. Retrieved 31 October 2014. Nucleic Acids Book (free online book on the ... AMP and GMP can then be converted into ATP and GTP, respectively, by kinases that add additional phosphates. ATP stimulates ...
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: 2640-2647. Katz AM, Repke DI, Dunnett J, Hasselbach W (1977). " ... "Phosphorylation of a 22,000-dalton component of the cardiac sarcoplasmic reticulum by adenosine 3', 5'- ...
This protein is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase (PKA) in cardiac muscle. The ... "The stimulation of calcium transport in cardiac sarcoplasmic reticulum by adenosine 3':5'-monophosphate-dependent protein ... kinase". J Biol Chem. 249 (19): 6174-80. PMID 4371608. Asahi, Michio; Sugita Yuji; Kurzydlowski Kazimierz; De Leon Stella; Tada ...
... 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 ... These mutations tend to confer increased sensitivity to tyrosine kinase inhibitors such as gefitinib and erlotinib. Of the ... Gefitinib is the first selective inhibitor of epidermal growth factor receptor's (EGFR) tyrosine kinase domain. Thus gefitinib ...
... adenosine-monophospate-activated protein kinase (AMPK) has also been found to be an effector for RHEB. AMPK is a protein kinase ... 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 ...
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 ...
For example, the cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) pathways appear to participate in neuronal ... When activated by the second messengers such as cAMP and calcium ions, enzymes such as PKA and MAP kinase can translocate to ... Nguyen, P. V., & Woo, N. H. (2003). Regulation of hippocampal synaptic plasticity by cyclic AMP-dependent protein kinases. ... Treisman, R. (1996). Regulation of transcription by MAP kinase cascades. Current Opinion in Cell Biology, 8(2), 205-215. ...
Increased levels of adenylyl cyclase, protein kinase A(PKA), and cyclic adenosine monophosphate induced PKA activity are also ... Glycogen synthase kinase 3 has been implicated in bipolar disorder, as bipolar medications lithium and valproate have been ... Phosphoinositide signaling is also altered, with elevated levels of phospholipase C, protein kinase C, and Gαq being reported ...
1985). "Studies on the phosphorylation of myelin basic protein by protein kinase C and adenosine 3':5'-monophosphate-dependent ... "Phosphorylation sites of bovine brain myelin basic protein phosphorylated with Ca2+-calmodulin-dependent protein kinase from ... protein kinase". J. Biol. Chem. 260 (23): 12492-9. PMID 2413024. Saxe DF, Takahashi N, Hood L, Simon MI (1985). "Localization ...
"Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase". Science. 253 (5018): ... The protein kinase C inhibitor bis(indolyl)maleimide inhibitor BIM1 is clearly seen in the structure of PKCiota (residue 574- ... BIM-1 and the related compounds BIM-2, BIM-3, and BIM-8 are bisindolylmaleimide-based protein kinase C (PKC) inhibitors. These ... The bound BIM1 inhibitor blocks the ATP-binding site and puts the kinase domain into an intermediate open conformation. The ...
CMP can be phosphorylated to cytidine diphosphate by the enzyme CMP kinase, with adenosine triphosphate or guanosine ...
Explained simply reversible protein phosphorylation works like this: a protein kinase moves a phosphate group from adenosine ...
The encoded protein is a type 1A regulatory subunit of protein kinase A. Inactivating germline mutations of this gene are found ... This revealed a Arg74His (Arginine to Histidine: Guanine (G)-> Adenosine (A) transition in the second codon position of the ...
Iodotubercidin is an adenosine kinase inhibitor that through its ability to increase levels of endogenous adenosine can enhance ... Effects of iodotubercidin on adenosine kinase activity and nucleoside transport in DDT1 MF-2 smooth muscle cells.. F E ... Effects of iodotubercidin on adenosine kinase activity and nucleoside transport in DDT1 MF-2 smooth muscle cells.. F E ... Effects of iodotubercidin on adenosine kinase activity and nucleoside transport in DDT1 MF-2 smooth muscle cells.. F E ...
Adenosine kinase inhibitors. 4. 6,8-Disubstituted purine nucleoside derivatives. Synthesis, conformation, and enzyme inhibition ... Adenosine kinase inhibitors. 4. 6,8-Disubstituted purine nucleoside derivatives. Synthesis, conformation, and enzyme inhibition ... 6,8-Disubstituted purine nucleosides were synthesized and evaluated as adenosine kinase inhibitors (AKIs). A method was ...
The uptake data suggest that adenosine kinase plays an important role in the metabolism of adenosine but indicate alternative ... The uptake data suggest that adenosine kinase plays an important role in the metabolism of adenosine but indicate alternative ... The uptake data suggest that adenosine kinase plays an important role in the metabolism of adenosine but indicate alternative ... The uptake data suggest that adenosine kinase plays an important role in the metabolism of adenosine but indicate alternative ...
The role of adenosine kinase in regulating adenosine concentration. Biochem J 1985, 226: 343-344. Boison D: Adenosine as a ... Gupta RS: Adenosine-AMP exchange activity is an integral part of the mammalian adenosine kinase. Biochem Mol Biol Int 1996, 39 ... Adenosine kinase (AdK; EC 2.7.1.20) is an enzyme that catalyzes the transfer of gamma-phosphate from Adenosine triphosphate ( ... Arch JR, Newsholme EA: Activities and some properties of 5-nucleotidase, adenosine kinase and adenosine deaminase in tissues ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Neonatal hepatic steatosis by disruption of the adenosine kinase gene. Detlev Boison, Louis Scheurer, Valérie Zumsteg, Thomas ... Neonatal hepatic steatosis by disruption of the adenosine kinase gene. Detlev Boison, Louis Scheurer, Valérie Zumsteg, Thomas ... Neonatal hepatic steatosis by disruption of the adenosine kinase gene Message Subject (Your Name) has sent you a message from ... Neonatal hepatic steatosis by disruption of the adenosine kinase gene. Detlev Boison, Louis Scheurer, Valérie Zumsteg, Thomas ...
Adenosine 3,5-Monophosphate-Dependent Protein Kinase from Brain Message Subject. (Your Name) has forwarded a page to you from ...
It can serve as a salvage mechanism for returning adenosine to nucleic acids. EC 2.7.1.20. ... An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. ... Adenosine Kinase. Subscribe to New Research on Adenosine Kinase An enzyme that catalyzes the formation of ADP plus AMP from ... 06/15/1994 - "Protective effect of an adenosine kinase inhibitor in septic shock.". 06/15/1994 - "One novel adenosine kinase ...
Adenosine kinase was purified 870-fold from rat heart by a combination of gel filtration and affinity chromatography. The ... Properties of rat heart adenosine kinase. M N Fisher, E A Newsholme ... In vivo the enzyme is likely to be saturated with both MgATP and adenosine. Indeed, the adenosine concentration in rat heart in ... The Km for MgATP was calculated to be 0.8 mM and that for adenosine, at likely physiological concentrations of MgATP and free ...
Adenosine kinase deficiency (ADK) in the liver can make it more susceptible to carcinogenic damage and may lead to liver cancer ... Adenosine kinase is a vital regulator of hepatic metabolism. Its deficiency in the liver causes hepatic steatosis and ... Low Adenosine Kinase in Liver may be a Risk Factor for Cancer Development. ... New study finds that reduced hepatic adenosine kinase expression (ADK) raises the susceptibility to the acute toxic effects of ...
Elevated adenosine signaling via adenosine A2B receptor induces normal and sickle erythrocyte sphingosine kinase 1 activity.. ... Elevated adenosine signaling via adenosine A2B receptor induces normal and sickle erythrocyte sphingosine kinase 1 activity ... Elevated adenosine signaling via adenosine A2B receptor induces normal and sickle erythrocyte sphingosine kinase 1 activity ... Elevated adenosine signaling via adenosine A2B receptor induces normal and sickle erythrocyte sphingosine kinase 1 activity ...
Intracerebroventricular infusion of glucose, insulin, and the adenosine monophosphate-activated kinase activator, 5- ... The AMP-activated kinase has been proposed to be an important intracellular energy sensor because the enzyme controls lipid and ... Although the above mechanisms are correlated with the regulation of AMP-activated kinase, the direct involvement of the enzyme ... evidence has shown that the AMP-activated kinase could control food intake. We show in this study that the ...
5-adenosine monophosphate-activated protein kinase (AMPK) modulates myoendothelial junctions 5-adenosine monophosphate- ... The 5-adenosine monophosphate-activated protein kinase (AMPK) is not only one of the most important enzymes controlling cell ... The 5-adenosine monophosphate-activated protein kinase (AMPK) is not only one of the most important enzymes controlling cell ... Qiu, Jiehua (2018): 5-adenosine monophosphate-activated protein kinase (AMPK) modulates myoendothelial junctions. Dissertation ...
... brucei can also salvage adenosine by adenosine kinase (AK). The efficient adenosine transport combined with a high-affinity AK ... Adenosine kinase mediates high affinity adenosine salvage in Trypanosoma brucei. Vodnala, Munender Umeå University, Faculty of ... T. brucei has a high affinity adenosine kinase (TbAK), which phosphorylates adenosine, deoxyadenosine (dAdo), inosine and their ... Trypanosoma brucei, adenosine kinase, thymidine kinase, methylthioadenosine phosphorylase, mouser ribonucleotide reductase, E. ...
... via metabolic clearance through adenosine kinase (ADK). Adult rats exposed to cranial irradiation (10 Gy) showed significant ... via metabolic clearance through adenosine kinase (ADK). Adult rats exposed to cranial irradiation (10 Gy) showed significant ... Among other gliotransmitters, astrocytes control the availability of adenosine, an endogenous neuroprotectant and modulator of ... These results confirm an astrocyte-mediated mechanism where preservation of extracellular adenosine can exert neuroprotection ...
Adenosine kinase (ADK) is considered to be the key regulator of the brains endogenous anticonvulsant, adenosine. In adult ... Astrogliosis in epilepsy leads to overexpression of adenosine kinase, resulting in seizure aggravation.. [Denise E Fedele, ... We therefore conclude that therapeutic strategies that augment the adenosine system after astrogliosis-induced upregulation of ...
Purpose: Adenosine kinase (ADK) represents the key metabolic enzyme for the regulation of extracellular adenosine levels in the ... Upregulation of adenosine kinase in astrocytes in experimental and human temporal lobe epilepsy. Journal. Epilepsia. Volume , ... astrocyte-based adenosine cycle and inflammation. Whether this interaction also can play a role in vivo needs to be further ...
Insights Into the Phosphoryltransfer Mechanism of Human Thymidylate Kinase Gained from Crystal Structures of Enzyme Complexes ... Human thymidylate kinase complexed with thymidine monophosphate, adenosine diphosphate and a magnesium-ion. *DOI: 10.2210/ ... THYMIDYLATE KINASE A 215 Homo sapiens EC#: 2.7.4.9 IUBMB Mutation: R200A, R183S, L184I, E190D, L191I Gene Name(s): DTYMK Gene ... ADENOSINE-5-DIPHOSPHATE. C10 H15 N5 O10 P2 XTWYTFMLZFPYCI-KQYNXXCUSA-N ...
Extracellular Adenosine Attenuates Left Ventricular Hypertrophy Through Its Impact on the Protein Kinase and Phosphatase ... Extracellular Adenosine Attenuates Left Ventricular Hypertrophy Through Its Impact on the Protein Kinase and Phosphatase ... Extracellular Adenosine Attenuates Left Ventricular Hypertrophy Through Its Impact on the Protein Kinase and Phosphatase ... Extracellular Adenosine Attenuates Left Ventricular Hypertrophy Through Its Impact on the Protein Kinase and Phosphatase ...
... energy status by preventing increases in AMP/ATP and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK ... Post-Meal Responses of Elongation Factor 2 (eEF2) and Adenosine Monophosphate-Activated Protein Kinase (AMPK) to Leucine and ... Post-Meal Responses of Elongation Factor 2 (eEF2) and Adenosine Monophosphate-Activated Protein Kinase (AMPK) to Leucine and ... "Post-Meal Responses of Elongation Factor 2 (eEF2) and Adenosine Monophosphate-Activated Protein Kinase (AMPK) to Leucine and ...
We hypothesized that inhibition of adenosine kinase exacerbates extracellular adenosine levels to reduce renal inflammation and ... the physiological effect of adenosine could be limited due to its phosphorylation by adenosine kinase. ... Adenosine kinase inhibition protects the kidney against streptozotocin-induced diabetes through anti-inflammatory and anti- ... Adenosine provides anti-inflammatory effects in cardiovascular disease via the activation of adenosine A2A receptors; however, ...
Adenosine triphosphate activates mitogen-activated protein kinase in human granulosa-luteal cells ... Inorganic lead activates the mitogen-activated protein kinase kinase-mitogen-activated protein kinase-p90(RSK) signaling ... Adenosine triphosphate-evoked cytosolic calcium oscillations in human granulosa-luteal cells: role of protein kinase C. Journal ... Adenosine 5'-triphosphate activates nuclear translocation of mitogen-activated protein kinases leading to the induction of ...
1. Both the monomer arginine kinase from lobster muscle and the dimer arginine kinase from Holothuria forskali catalyse the ATP ... E O Anosike, D C Watts; Effects of arginine and some analogues of the partial adenosine triphosphate-adenosine diphosphate ... and some analogues of the partial adenosine triphosphate-adenosine diphosphate exchange reaction catalysed by arginine kinase. ... Evolutionary divergence in the mechanism of action of a monomer and a dimer arginine kinase E O Anosike E O Anosike ...
Kinetics of Adenosine 3′:5′-Monophosphate-dependent Protein Kinase Activation and Inhibition of Thymidine Incorporation into ... Kinetics of Adenosine 3′:5′-Monophosphate-dependent Protein Kinase Activation and Inhibition of Thymidine Incorporation into ... Kinetics of Adenosine 3′:5′-Monophosphate-dependent Protein Kinase Activation and Inhibition of Thymidine Incorporation into ... Kinetics of Adenosine 3′:5′-Monophosphate-dependent Protein Kinase Activation and Inhibition of Thymidine Incorporation into ...
Calbiochem The Adenosine Kinase Inhibitor, also referenced under CAS 214697-26-4, controls the biological activity of Adenosine ... Kinase. This small molecule/inhibitor is primarily used for Phosphorylation & Dephosphorylation applications. - Find MSDS or ... Adenosine Kinase. Primary Target IC,sub,50,/sub,. 50.7 nM inhibiting adenosine kinase (AK) using intact IMR-32 cells and 1.7 nM ... The Adenosine Kinase Inhibitor, also referenced under CAS 214697-26-4, controls the biological activity of Adenosine Kinase. ...
InhibitorsPathwayMetabolismPhosphorylateCharacterizationMonophosphate activatedDeaminaseReceptorsLevels of adenosineEffect of adenosineDeficiencyMitogen activatEnzyme that catalyzesEffects of adenosineAdenineSignaling pathwayCatalyticPharmacologicalPurineSubstrateRole of Adenosine1.20InosinePhosphorylation of adenosineAssayCAMP-dependHuman adenosine kinase1998ConcentrationsHypoxiaExtracellular signal-ModulatesMAPKVitroReceptor antagonistsGeneInflammationVivoDeoxyadenosineInhibition ProtectsSynaptic transmissionDeficientBoisonOverexpressionPhysiological
- Adenosine kinase inhibitors. (mysciencework.com)
- 6,8-Disubstituted purine nucleosides were synthesized and evaluated as adenosine kinase inhibitors (AKIs). (mysciencework.com)
- Furthermore, L. donovani extracts could slowly catalyze the deamination of formycin A. The isolation and characterization of adenosine kinase-deficient cells has provided considerable insight into the function of the purine pathway in L. donovani. (elsevier.com)
- The uptake data suggest that adenosine kinase plays an important role in the metabolism of adenosine but indicate alternative metabolic pathways for this nucleoside. (elsevier.com)
- The metabolism of adenosine to the nucleotide level in TUBA2 cells appears to be initiated via deribosylation to adenine. (elsevier.com)
- Mutant cell extracts, unlike those prepared from wildtype cells, did not phosphorylate radiolabelled adenosine, tubercidin, or formycin A. Intact adenosine kinase-deficient cells did not accumulate exogenous tubercidin or formycin A but incorporated [ 14 C]adenosine at rates 25% of those found for parental cells. (elsevier.com)
- Iovannisci, DM & Ullman, B 1984, ' Characterization of a mutant Leishmania donovani deficient in adenosine kinase activity ', Molecular and Biochemical Parasitology , vol. 12, no. 2, pp. 139-151. (elsevier.com)
- Intracerebroventricular infusion of glucose, insulin, and the adenosine monophosphate-activated kinase activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, controls muscle glycogen synthesis. (nih.gov)
- The 5'-adenosine monophosphate-activated protein kinase (AMPK) is not only one of the most important enzymes controlling cell catabolic metabolism, but has been shown to influence vascular tone, thereby augmenting blood and oxygen supply as required for catabolic pathways. (uni-muenchen.de)
- Qiu, Jiehua (2018): 5'-adenosine monophosphate-activated protein kinase (AMPK) modulates myoendothelial junctions. (uni-muenchen.de)
- Consistent with MPS findings, the supplements maintained elongation activity and cellular energy status by preventing increases in AMP/ATP and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase ACC and eEF2. (mdpi.com)
- Abhishek Thakur, Nirnoy Dan, Soumendranath Bhakat, Venkatesan Jayaprakash and Sugato Banerjee, "5' Adenosine Monophosphate-Activated Protein Kinase Modulators as Anticancer Agents", Anti-Cancer Agents in Medicinal Chemistry (2016) 16: 961. (eurekaselect.com)
- Adenosine monophosphate-activated protein kinase activation, substrate transporter translocation, and metabolism in the contracting hyperthyroid rat heart. (ox.ac.uk)
- Adenosine monophosphate-activated protein kinase (AMPK) has been proposed to stimulate mitochondrial biogenesis and fat and glucose metabolism in skeletal muscle. (elsevier.com)
- Killer Cell Lectin-like Receptor G1 Inhibits NK Cell Function through Activation of Adenosine 5'-Monophosphate-Activated Protein Kinase. (ox.ac.uk)
- The 5′ adenosine monophosphate-activated protein kinase (AMPK) is a heterotrimeric, evolutionary conserved enzyme which has emerged as a critical regulator of skeletal muscle cellular bioenergetics. (edu.au)
- Preconditioning' with latrepirdine, an adenosine 5'-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1(G93A) mice. (rcsi.com)
- Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a master regulator of energy balance. (rcsi.com)
- Subsequently, we provide in vivo genetic evidence that adenosine deaminase (ADA) deficiency leads to excess plasma adenosine and elevated erythrocyte SphK1 activity. (nih.gov)
- Under conditions in which extensive metabolism of intracellular adenosine was present, [3H]adenosine accumulation by DDT1 MF-2 cells was almost completely inhibited by iodotubercidin and the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)-adenine or by the nucleoside transport inhibitor nitrobenzylthioinosine. (aspetjournals.org)
- VSMCs had been incubated with cytomix comprising 10?ng/mL interleukin (IL)-1β 10 interferon (IFN)-γ … In activated VSMCs from non-diabetic rats the adenosine deaminase inhibitor erythro -9-(2-Hydroxy-3-nonyl)adenine (EHNA) decreased iNOS synthesis as the ENT inhibitor S-(4-Nitrobenzyl)-6-thioinosine (NBTI) improved it as well as the Compact disc73 inhibitor α β-Methylene-ADP (AOPCP) was inadequate (Fig.?2a). (exposed-skin-care.net)
- Together with adenosine deaminase, adenosine kinase regulates intra- and extracellular cellular adenosine concentration. (novocib.com)
- One of the mutant clones, S49-dA2, was further subjected to selection in a medium containing 2 μCi/ml tritiated deoxyadenosine and 1 μg/ml deoxycoformycin, an inhibitor of adenosine deaminase. (utmb.edu)
- Adenosine dysregulation can cause various pathologies, exemplified by a deficiency in adenosine deaminase in severe combined immunodeficiency. (biologists.org)
- We have established a Drosophila model to study the effects of increased adenosine in vivo by mutating the main Drosophila adenosine deaminase-related growth factor (ADGF-A). Using a genetic screen, we show here that the increased extracellular adenosine in the adgf-a mutant is associated with hyperglycemia and impairment in energy storage. (biologists.org)
- A genetic deficiency of adenosine deaminase (ADA) is accompanied by greatly elevated levels of its substrates adenosine and deoxyadenosine. (biologists.org)
- In animals, there are two groups of enzymes with adenosine deaminase activity, referred to as ADA1 and ADA2. (biologists.org)
- The half-life of extracellular adenosine is on the order of seconds, as it is removed from the extracellular space either by adenosine deaminase, which converts it to inosine, or by cellular reuptake via equilibrative or concentrative nucleoside transporters ( 6 , 7 ). (jimmunol.org)
- Accordingly, we tested Ap(n)As for their effects on the in vitro activities of adenosine kinase, adenosine deaminase, AMP deaminase and 5'-nucleotidase and, following unilateral microinjections in rat striatum, on in vivo levels of endogenous adenosine. (nebraska.edu)
- 0.05) by 48% with Ap 4 A and by 37% with AppCH 2 ppA, a metabolically stable analogue of Ap 4 A. Striatal levels of adenosine were not affected significantly by Ap 5 A or Ap 6 A. Cytosolic, but not particulate 5'-nucleotidase activity was inhibited and AMP deaminase activity was increased by some Ap(n)As. (nebraska.edu)
- The serendipitous discovery of adenosine deaminase (ADA) deficiency in two patients with cellular immunodeficiency in 1972 by Dr. Eloise Giblett and colleagues ( 1 ) ushered in a new era in the investigation of the molecular mechanisms underlying primary immunodeficiency disorders. (jimmunol.org)
- Finally, extracellular adenosine is rapidly taken up into the cells and metabolized either into inosine by adenosine deaminase or into AMP by adenosine kinase. (nature.com)
- Adenosine deaminase inhibition attenuated the cytoprotective effect of adenosine but not of inosine during COGD. (biomedsearch.com)
- At these time points, the activity of adenosine deaminase was measured in isolated lymphocytes, and forearm blood flow (FBF) was determined by venous occlusion plethysmography during administration of adenosine and dipyridamole into the brachial artery. (bmj.com)
- 4 Degradation of adenosine by the enzymes adenosine deaminase and adenosine kinase, however, is confined to the intracellular compartment. (bmj.com)
- Although activation of A 3 adenosine receptors attenuates reperfusion lung injury and associated apoptosis, the signaling pathway that mediates this protection remains unclear. (springer.com)
- The objective of this study was to determine whether primary hepatic stellate cells produce collagen in response to adenosine (via activation of adenosine A 2A receptors) and to further determine the signaling mechanisms involved in adenosine A 2A receptor-mediated promotion of collagen production. (aspetjournals.org)
- Likewise, LX-2 cells, a human HSC line, increases expression of procollagen αI and procollagen αIII mRNA and their translational proteins, collagen type I and type III, in response to pharmacological stimulation of adenosine A 2A receptors. (aspetjournals.org)
- These results indicate that adenosine A 2A receptors signal for increased collagen production by multiple signaling pathways. (aspetjournals.org)
- These results provide strong evidence in support of the hypothesis that adenosine receptors promote hepatic fibrosis, at least in part, via direct stimulation of collagen expression and that signaling for collagen production proceeds via multiple pathways. (aspetjournals.org)
- Beta-Adrenoceptor-medicated down-regulation of M2 muscarinic receptors: role of cyclic adenosine 5'-monophosphate-dependent protein kinase and protein kinase C. (aspetjournals.org)
- Procaterol-induced down-regulation of M2 receptors was fully blocked by N-[2-(methylamino)ethyl]-5'-isoquinoline-sulfonamide and 2-[1-(3-dimethylaminopropyl)-inol-3-yl]-3-(indol-3-yl)maleimide, implicating both of these kinases in the M2 muscarinic receptor down-regulation. (aspetjournals.org)
- Although, adenosine activating its receptors (A 1 , A 2A , A 2B and A 3 ) is able to differentially modulate the function of adipocytes and macrophages, in order to avoid the reduction of insulin sensitivity and generate an anti-inflammatory state in subject with obesity. (elsevier.es)
- Adenosine A 1 receptors (A 1 Rs) have been shown to be involved in antinociception in preclinical models for several decades. (springer.com)
- Bailey A, Matthes H, Kieffer B, Slowe S, Hourani SMO, Kitchen I (2002) Quantitative autoradiography of adenosine receptors and NBTI-sensitive adenosine transporters in the brains and spinal cords of mice deficient in the μ-opioid receptor gene. (springer.com)
- During cerebral metabolic stress, such as hypoxia or ischemia, the increase in extracellular adenosine inhibits excitatory synaptic transmission onto vulnerable neurons via presynaptic adenosine A 1 receptors, thereby reducing the activation of postsynaptic glutamate receptors. (jneurosci.org)
- Adenosine regulates cellular functions by binding to G-protein-coupled adenosine receptors (A1, A2a, A2b and A3 in mammals) that can regulate intracellular cAMP ( Latini and Pedata, 2001 ). (biologists.org)
- Cells that express one or more of the four G protein-coupled adenosine receptors (AR) subtypes (A1, A2A, A2B, and/or A3) have the capacity to respond to extracellular adenosine. (jimmunol.org)
- Background- Endogenous adenosine can protect the overloaded heart against the development of hypertrophy and heart failure, but the contribution of A 1 receptors (A 1 R) and A 3 receptors (A 3 R) is not known. (ahajournals.org)
- 2-5 A 1 receptors (A 1 R) and A 3 receptors (A 3 R) are expressed in cardiomyocytes, and a substantial body of evidence indicates that adenosine can protect the heart during and after an ischemic insult. (ahajournals.org)
- 6,7 Liao et al 8 demonstrated that the adenosine analogue 2-chloroadenosine (CADO) also attenuated pressure overload-induced LV hypertrophy through activation of the A 1 R. Similar to A 1 R, the A 3 R are Gi protein-coupled receptors that have been shown to activate similar downstream signaling pathways. (ahajournals.org)
- Adenosine acts through four G protein-coupled adenosine receptors that either stimulate (A 2A , A 2B ) or inhibit (A 1 , A 3 ) adenylate cyclase and thus enhance or decrease the second messenger cyclic AMP (cAMP). (nature.com)
- Blockade of adenosine A 2A receptors (A 2A R) affords robust neuroprotection in a number of brain conditions, although the mechanisms are still unknown. (biomedcentral.com)
- CONCLUSIONS AND IMPLICATIONS: The cytoprotection elicited by adenosine and inosine in a model of renal ischaemia involved both interactions with cell surface adenosine receptors on renal tubular epithelial cells and intracellular metabolism and conversion of adenosine to ATP. (biomedsearch.com)
- 5 There are four types of G-protein coupled adenosine receptor, which are designated A 1 , A 2A , A 2B , and A 3 receptors. (bmj.com)
- Manipulation of endogenous levels of adenosine by inhibiting adenosine kinase represented a promising novel approach, but development in this area is no longer active. (springer.com)
- Astrogliosis is a neuropathological hallmark of epilepsy, whatever the etiology is, and astrogliosis is frequently associated with overexpression of adenosine kinase, which means downregulation of synaptic levels of adenosine. (currentdrugtargets.com)
- Adenosine kinase is ubiquitous in eukaryotes and is a key enzyme in the regulation of the intracellular levels of adenosine, an important physiological effector of many cells and tissues. (pomposity.us)
- Although adenosine is typically produced inside a cell, extracellular levels of adenosine rise as a consequence of the catabolism of ATP that is released from stressed or damaged cells ( 3 , 4 ). (jimmunol.org)
- Measurements of purine metabolites in the body fluids of ADA-deficient patients showed elevated levels of adenosine ( 3 ), one of the two substrates for ADA. (jimmunol.org)
- however, the physiological effect of adenosine could be limited due to its phosphorylation by adenosine kinase. (sigmaaldrich.com)
- Cultured hippocampal neurons from neonatal rats were used to investigate the effect of adenosine on the release of glutamate. (mysciencework.com)
- Conclusions- Adenosine exerts protective effects on the overloaded heart, but the A 3 R acts counter to the protective effect of adenosine. (ahajournals.org)
- A low-methionine diet can be beneficial in patients with methionine adenosyltransferase I/III deficiency if plasma methionine concentrations exceed 800 μmol/L. There is some evidence that this diet may also be beneficial in patients with S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies. (springer.com)
- Diseases associated with ADK include Hypermethioninemia Due To Adenosine Kinase Deficiency and Hypermethioninemia . (genecards.org)
- the purpose of this study was therefore to determine whether A 3 adenosine receptor stimulation with reperfusion modulates expression of the different mitogen-activated protein kinases. (springer.com)
- The effect of SCH58261 on the IL-1β-induced phosphorylation of the mitogen-activated protein kinases (MAPKs) c-Jun N-terminal kinase (JNK) and p38 was evaluated by western blotting and immunocytochemistry. (biomedcentral.com)
- An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. (curehunter.com)
- Adenosine kinase is a ubiquitous enzyme that catalyzes the transfer of γ-phosphate from ATP to 5'-hydroxyl of adenosine (AR), an important modulator of central nervous system functions and a signal molecule involved in hypoxia, inflammation, and nociception. (novocib.com)
- Adenosine kinase (AK) is a cytosolic enzyme that catalyzes the conversion of adenosine to AMP. (medchemexpress.cn)
- In enzymology, an adenylyl-sulfate kinase (EC 2.7.1.25) is an enzyme that catalyzes the chemical reaction ATP + adenylyl sulfate ⇌ {\displaystyle \rightleftharpoons } ADP + 3'-phosphoadenylyl sulfate Thus, the two substrates of this enzyme are ATP and adenylyl sulfate, whereas its two products are ADP and 3'-phosphoadenylyl sulfate. (wikipedia.org)
- Cytoprotective effects of adenosine and inosine in an in vitro model of acute tubular necrosis. (biomedsearch.com)
- The selective A(3) adenosine receptor antagonist MRS 1523 attenuated the protective effects of adenosine and inosine, while an A(3) adenosine receptor agonist provided a partial protective effect. (biomedsearch.com)
- We have found that the pathogen Trypanosoma brucei, which causes African sleeping sickness, has a very efficient salvage of adenosine, deoxyadenosine and adenosine analogs such as adenine arabinoside (Ara-A). One of the conclusions made was that this nucleoside analog is phosphorylated by the T. brucei adenosine kinase and kills the parasite by causing nucleotide pool imbalances and by incorporation into nucleic acids. (diva-portal.org)
- The present study was designed to examine the effect of ATP on activation of the mitogen-activated protein kinase (MAPK) signaling pathway and its physiological role in human granulosa-luteal cells. (eurekamag.com)
- Antiserum against the catalytic subunit of adenosine 3′:5′-cyclic monophosphate-dependent protein kinase. (biochemj.org)
- An antiserum against the catalytic subunit C of cyclic AMP-dependent protein kinase, isolated from bovine heart type II protein kinase, was produced in rabbits. (biochemj.org)
- Comparative immunotitration of protein kinases showed that the amount of antiserum required to eliminate 50% of the enzymic activity was identical for pure catalytic subunit, and for holoenzymes type I and type II. (biochemj.org)
- Immunotitration of the protein kinase catalytic subunit C from rat liver revealed that the antibodies had rather similar reactivities towards the rat liver and the bovine heart enzyme. (biochemj.org)
- Catalytic subunit of adenosine cyclic 2',5'monophosphate-dependent protein kinase from rat muscle: basic properties and factors influencing the activity. (semanticscholar.org)
- The catalytic (C) subunit of isoenzyme II of cyclic AMP-dependent protein kinase from rat muscle, purified to apparent homogeneity, was investigated for some of its basic properties and factors that influence its activity. (semanticscholar.org)
- A rabbit anti-S6/H4 kinase peptide (SVIDPVPAPVGDSHVDGAAK) antibody recognized both the S6/H4 kinase holoenzyme and catalytic domain. (unt.edu)
- Abl contains 407 amino acids (residues 237-643 of the p120-gag-abl polyprotein), which include the kinase catalytic domain, SH2 domain on the N-terminus and the I237M mutation. (neb.com)
- Further studies should confirm if adenosine kinase represents a new biomarker or a pharmacological target in liver cancer," says Editor-in-Chief of Journal of Caffeine and Adenosine Research Sergi Ferr , MD, PhD, and his research colleagues in the Integrative Neurobiology Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD. (medindia.net)
- Next, using 4 adenosine receptor-deficient mice and pharmacological approaches, we determined that the A2B adenosine receptor (ADORA2B) is essential for adenosine-induced SphK1 activity in human and mouse normal and sickle erythrocytes in vitro. (nih.gov)
- We show in this study that the intracerebroventricular infusion of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), a pharmacological AMP-activated kinase activator, increased insulin-stimulated muscle glycogen synthesis and insulin sensitivity during a hyperinsulinemic clamp. (nih.gov)
- blend for 24?h in the existence or lack of (1) exogenous adenosine and related substances and/or (2) pharmacological real estate agents affecting adenosine turnover. (exposed-skin-care.net)
- Pharmacological inhibition of NOS abolished adenosine-induced vasorelaxation in aortic tissues from diabetic but not nondiabetic animals. (exposed-skin-care.net)
- Pharmacological manipulation of this kinase should be considered as a therapeutic modality in the future. (sun.ac.za)
- The preparation was free of purine-metabolizing enzymes that could interfere in the assay of the kinase. (biochemj.org)
- Furthermore, L. donovani extracts could slowly catalyze the deamination of formycin A. The isolation and characterization of adenosine kinase-deficient cells has provided considerable insight into the function of the purine pathway in L. donovani. (elsevier.com)
- Adenosine is an endogenous purine nucleoside that has multiple functions. (biologists.org)
- Adenosine is an endogenous purine nucleoside that modulates a wide range of physiological functions ( 1 ). (jimmunol.org)
- Adenosine is a purine-nucleoside that is formed both intra- and extracellularly by degradation of adenosine monophosphate (AMP) (fig 1). (bmj.com)
- Indeed, the adenosine concentration in rat heart in vivo is probably sufficient to cause substrate inhibition, and this would be increased by an increase in free Mg2+ concentration. (biochemj.org)
- The Mg2+-nucleotide complex is the substrate for this as it is for the kinase reaction. (portlandpress.com)
- Enzymatic activity of adenosine kinase with particular nucleoside substrate is measured by spectrophotometric assays in a coupled lactate dehydrogenase / pyruvate kinase system. (novocib.com)
- 8 ) that deoxyadenosine, the other substrate of ADA, rather than adenosine, was the toxic metabolite in this disease. (jimmunol.org)
- Nucleoside kinase with broad substrate specificity. (uniprot.org)
- Given the vital neuroprotective role of adenosine, these findings suggest that depletion of adenosine may underlie the increased neuronal vulnerability to repetitive or secondary hypoxia/ischemia in cerebrovascular disease and head injury. (jneurosci.org)
- Other members of this family (also known as the RK family) include ribokinase (RK), inosine-guanosine kinase, fructokinase, and 1-phosphofructokinase. (wikipedia.org)
- Adenosine can be metabolized by ADA or ADK into inosine and AMP, respectively. (pnas.org)
- One unit of adenosine kinase converts 1.0 µmole of inosine and ATP to IMP and ADP per minute at pH 8 at 37 C, as measured by a coupled IMPDH enzyme system. (novocib.com)
- We specifically investigated the course of the adenosine release, its concentrations and that of its metabolite inosine and were further interested, if and to what degree the adaptation to these standardized living conditions are linked to adenosine profiles and different physiologic states. (nature.com)
- Inosine-guanosine kinase ( EC:2.7.1.73 ) (gene gsk). (ebi.ac.uk)
- Inhibition of adenosine kinase reduced the protective effects of both adenosine and inosine during COGD. (biomedsearch.com)
- Pretreatment of the cells with adenosine or inosine markedly protected against the fall in cellular ATP content in the cells subjected to COGD. (biomedsearch.com)
- ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives. (genecards.org)
- For rapid evaluation of substrates properties of novel nucleoside analogs for human adenosine kinase see our PRECICE ADK Phosphorylation Assay Kit . (novocib.com)
- Furthermore, a role is suggested for cAMP-dependent kinase and PKC in M2 muscarinic receptor down-regulation and their functional desensitization. (aspetjournals.org)
- NOVO CIB 's human adenosine kinase is an active and purified, 345-aa short form (14,2) ADK protein ( 39kDa) cloned by RT-PCR amplification of mRNA extracted from human hepatoma cells and expressed in E.coli . (novocib.com)
- Specific inflammatory stimuli, such as bacterial products, are also capable of triggering adenosine release from immune cells ( Bodin and Burnstock, 1998 ). (biologists.org)
- The Km for MgATP was calculated to be 0.8 mM and that for adenosine, at likely physiological concentrations of MgATP and free MgCl2, was about 0.2 microM. (biochemj.org)
- Changes in the concentrations of adenosine and free Mg2+ may play a role in modifying the activity of the enzyme in vivo. (biochemj.org)
- These data suggest that iodotubercidin, at pharmacologically relevant concentrations, inhibits nucleoside transport independently of its well characterized inhibition of adenosine kinase and that N-methyl-D-glucamine must be used with caution in experiments to determine the possible presence of Na+ gradient-dependent concentrative nucleoside transporters. (aspetjournals.org)
- Concentrations of adenosine related metabolites and substances thereof were assayed by HPLC. (exposed-skin-care.net)
- Addition of high concentrations of adenosine and its precursors or analogues enhanced iNOS formation solely in diabetic VSMCs. (exposed-skin-care.net)
- As hypoxia does not allow sufficient and oxygen dependent re-phosphorylation of ADP and AMP, adenosine concentrations could increase as a function of hypoxia. (nature.com)
- We hypothesized that adenosine concentrations would be enhanced during the early stages of both hypoxic interventions. (nature.com)
- Our unexpected additional finding of hypoxia-independent adenosine increase has initiated further analysis to i) identify a potential role of hemolysis as a source of adenosine in our experimental interventions, ii) to evaluate the interaction of adenosine and endothelial barrier function, and iii) to investigate the impact of physical activity on adenosine concentrations. (nature.com)
- Animal studies suggest that the anti-inflammatory effect of methotrexate (MTX) is mediated by increased adenosine concentrations. (bmj.com)
- Instead, by using the selective A 1 antagonist 8-cyclopentyl-1,3-dipropylxanthine and a novel adenosine sensor, we demonstrate that adenosine production is reduced with repeated episodes of hypoxia. (jneurosci.org)
- We have shown that the adenosine-dependent depression of excitatory synaptic transmission during hypoxia is weakened by previous exposure to hypoxia. (jneurosci.org)
- Direct measurement of adenosine release during hypoxia revealed reduced production of adenosine. (jneurosci.org)
- However, by giving exogenous adenosine or prolonged inter-episode recovery intervals, the sensitivity of synaptic transmission to hypoxia can be partially restored. (jneurosci.org)
- Extracellular adenosine is an important signaling molecule in neuromodulation, immunomodulation and hypoxia. (biologists.org)
- The release of adenosine in some tissues has been shown to be stimulated by hypoxia ( Buck, 2004 ). (biologists.org)
- The PlanHab study investigated microgravity through inactivity in bed rest and normobaric hypoxia to examine their independent or combined effect on adenosine and its kinetics. (nature.com)
- Our hypothesis of a hypoxia-triggered increase in adenosine was confirmed in HAMB but unexpectedly also in NBR. (nature.com)
- We investigated the changes in adenosine release and its kinetics under simulated space conditions by subjecting 14 male subjects to 21 days of hypoxia and/or horizontal bed rest to mimic microgravity effects. (nature.com)
- Three major MAPK families have been identified: the extracellular signal-regulated kinases (ERKs), the c-Jun amino-terminal protein kinases (JNKs) and the p38 kinases. (springer.com)
- Moreover, interplay among chloroplastic signalling networks and plasma membrane receptor kinases is emerging as a key mechanism that modulates stress responses in plants. (royalsocietypublishing.org)
- Western blot analysis, using a monoclonal antibody that detected the phosphorylated forms of extracellular signal-regulated kinase-1 and -2 (p42(mapk) and p44 (mapk), respectively), demonstrated that ATP activated MAPK in a dose- and time-dependent manner. (eurekamag.com)
- It has been suggested that all triggers are linked to a common final pathway, for example, activation of protein kinase C (PKC) and/or the mitogen-activated kinases (MAPKs), in particular p38 MAPK. (sun.ac.za)
- Both these cyclic nucleotides transiently activate the downstream stress kinase, p38 MAPK, which may trigger further downstream adaptive processes. (sun.ac.za)
- The recognition of an external factor initiates a convergent sequence of events where the activation of the mitogen-activated protein kinase (MAPK) pathway is paralleled by changes in cytoplasmic calcium concentration, activation of calcium-dependent protein kinase (CDPK) cascades and rapid NADPH oxidase-driven burst of reactive oxygen species (ROS) in the apoplast. (royalsocietypublishing.org)
- Recognition of conserved microbial patterns (PAMPs) by plasma membrane receptor kinases launches the activation of mitogen-activated protein kinase (MAPK) cascades, formation of calcium transients, calcium-dependent protein kinases (CDPKs) and apoplastic reactive oxygen species (ROS) burst through NADPH oxidase activity. (royalsocietypublishing.org)
- Outcomes Treatment with adenosine-degrading enzymes or receptor antagonists increased development in activated VSMCs from nondiabetic and diabetic rats iNOS. (exposed-skin-care.net)
- Abo-Salem OM, Hayallah AM, Bilkei-Gorzo A, Filipek B, Zimmer A, Müller CE (2004) Antinociceptive effects of novel A 2B adenosine receptor antagonists. (springer.com)
- The roles of adiponectin, a PPAR-γ regulated pleiotropic adipokine, in regulating the response of fibroblasts and in mediating the effects of PPAR-γ are unknown.Methods: Regulation of fibrotic gene expression and TGF-ß signaling by adiponectin and adenosine monophosphate protein-activated (AMP) kinase agonists were examined in normal fibroblasts in monolayer cultures and in three-dimensional skin equivalents. (northwestern.edu)
- ADK (Adenosine Kinase) is a Protein Coding gene. (genecards.org)
- Gene Ontology (GO) annotations related to this gene include adenosine kinase activity . (genecards.org)
- Even though the in vivo role of both ADNs is still uncertain, due to their lack or low activity on Ado there may yet be the ADN gene in the Arabidopsis genome which likely acts on both adenosine and cytokinin ribosides. (uwaterloo.ca)
- Cloning and expression of the adenosine kinase gene from rat and human tissues. (pomposity.us)
- The "complex of myxomas, spotty skin pigmentation, and endocrine overactivity," or "Carney complex" (CNC), is caused by inactivating mutations of the regulatory subunit type 1A of the cAMP-dependent protein kinase (PRKAR1A) gene and as yet unknown defect(s) in other gene(s). (cdc.gov)
- 1-phosphofructokinase ( EC:2.7.1.56 ) (fructose 1-phosphate kinase) (gene fruK). (ebi.ac.uk)
- Tagatose-6-phosphate kinase ( EC:2.7.1.144 ) (phosphotagatokinase) (gene lacC). (ebi.ac.uk)
- Nucleotide sequence of the Rhodobacter capsulatus fruK gene, which encodes fructose-1-phosphate kinase: evidence for a kinase superfamily including both phosphofructokinases of Escherichia coli. (ebi.ac.uk)
- Sequence similarities between the gene specifying 1-phosphofructokinase (fruK), genes specifying other kinases in Escherichia coli K12, and lacC of Staphylococcus aureus. (ebi.ac.uk)
- We hypothesized that inhibition of adenosine kinase exacerbates extracellular adenosine levels to reduce renal inflammation and injury in streptozotocin-induced diabetes. (sigmaaldrich.com)
- Bilkei-Gorzo A, Abo-Salem OM, Hayallah AM, Michel K, Müller CE, Zimmer A (2008) Adenosine receptor subtype-selective antagonists in inflammation and hyperalgesia. (springer.com)
- Extracellular adenosine has an important role in regulating the severity of inflammation during an immune response. (jimmunol.org)
- During inflammation, increases in extracellular adenosine levels effectively turn off the local inflammatory response to protect against excessive cellular damage to the surrounding tissue ( 2 ). (jimmunol.org)
- Because adenosine has such potent effects on inflammation, modulators of adenosine signaling are being evaluated as potential therapeutic options for diseases that have an inflammatory component ( 8 ). (jimmunol.org)
- In vivo the enzyme is likely to be saturated with both MgATP and adenosine. (biochemj.org)
- Elevated plasma adenosine induces erythrocyte SphK1 activity increase in vivo. (nih.gov)
- Since S6/H4 kinase is homologous with rac-activated PAK65, the observation that phosphorylation is also required for activation suggests a complex mechanism for in vivo activation of the S6/H4 kinase. (unt.edu)
- One of the subclones, S49-12, was completely devoid of adenosine kinase and was partially deficient in deoxyadenosine kinase. (utmb.edu)
- DEAE chromatography of the wild-type cell extracts revealed two deoxyadenosine phosphorylating activities, one of which coeluted with adenosine kinase and was the enzyme missing in S49-12. (utmb.edu)
- Subsequent experimentation showed that deoxyadenosine is converted first to 2′-deoxyadenosine 5′-monophosphate and finally to dATP by the high levels of deoxynucleoside kinases in the thymus. (jimmunol.org)
- Adenosine kinase inhibition protects the kidney against streptozotocin-induced diabetes through anti-inflammatory and anti-oxidant mechanisms. (sigmaaldrich.com)
- Bagley EE, Vaughan CW, Christie MJ (1999) Inhibition by adenosine receptor agonists of synaptic transmission in rat periaqueductal grey neurons. (springer.com)
- Lowering adenosine by ADA enzyme therapy or genetic deletion of ADORA2B significantly reduced excess adenosine-induced erythrocyte SphK1 activity in ADA-deficient mice. (nih.gov)
- Mutant cell extracts, unlike those prepared from wildtype cells, did not phosphorylate radiolabelled adenosine, tubercidin, or formycin A. Intact adenosine kinase-deficient cells did not accumulate exogenous tubercidin or formycin A but incorporated [ 14 C]adenosine at rates 25% of those found for parental cells. (elsevier.com)
- Iovannisci, DM & Ullman, B 1984, ' Characterization of a mutant Leishmania donovani deficient in adenosine kinase activity ', Molecular and Biochemical Parasitology , vol. 12, no. 2, pp. 139-151. (elsevier.com)
- 1. D. Boison (2013) Adenosine kinase: exploitation for therapeutic gain. (novocib.com)
- Boison D, Chen JF, Fredholm BB (2010) Adenosine signalling and function in glial cells. (springer.com)
- Astrogliosis in epilepsy leads to overexpression of adenosine kinase, resulting in seizure aggravation. (sigmaaldrich.com)
- Erythrocyte possesses high sphingosine kinase 1 (SphK1) activity and is the major cell type supplying plasma sphingosine-1-phosphate, a signaling lipid regulating multiple physiological and pathological functions. (nih.gov)