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)

TY - JOUR. T1 - Characterization of a mutant Leishmania donovani deficient in adenosine kinase activity. AU - Iovannisci, David M.. AU - Ullman, Buddy. PY - 1984/6. Y1 - 1984/6. N2 - From a mutagenized population of wildtype Leishmania donovani promastigotes, a clonal cell line, TUBA2, was isolated by virtue of its ability to survive and grow in 20 μM tubercidin (7-deazaadenosine). The TUBA2 clone was also 1000-fold less sensitive than the parental line to growth inhibition by formycin A, another cytotoxic adenosine analog. Parental and mutant cells, however, were equally sensitive to growth inhibition by formycin B, allopurinol riboside, and 6-thioguanosine. 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 [14C]adenosine at rates 25% of those found for parental cells. The uptake data suggest that ...
Adenosine kinase inhibitors. 4. 6,8-Disubstituted purine nucleoside derivatives. Synthesis, conformation, and enzyme inhibition.: 6,8-Disubstituted purine nucle
Sigma-Aldrich offers abstracts and full-text articles by [Chelsey Pye, Nehal M Elsherbiny, Ahmed S Ibrahim, Gregory I Liou, Ahmed Chadli, Mohamed Al-Shabrawey, Ahmed A Elmarakby].
Utilizing decision making biomarkers in drug development requires thorough assay validation. non-human primate toxicology study using these assays, we demonstrated a 1500-fold and a 3000-fold increase in total A42 in plasma, a 4-fold and 8-fold increase in total A42 in CSF together with a 95% and 96% reduction of free A42 in CSF following weekly intravenous injections of 10?mg/kg and 100?mg/kg, respectively. Levels of A40 were unchanged. The accuracy of these data is supported by previous pre-clinical studies as well as predictive pharmacokinetic/pharmacodynamics modeling. In contrast, when analyzing the same non-human primate samples excluding the pre-treatment steps, we were not able to distinguish between free and total A42. Our data clearly demonstrate the importance of thorough evaluation of antibody interference and appropriate validation to monitor different types of biomarkers in the presence of a therapeutic antibody. and collected into pre-chilled polypropylene Eppendorf tubes (0.5?mL ...
This immunocytochemical study evaluates the presence of IgG1C4, IgA and IgE immunoglobulins in active lesions of 25 localized cutaneous leishmaniasis patients from three bioclimatic areas (Awa, Afa and Bsha) in Mrida State, Venezuela. regularly in patients through the Awa region than in those through the Bsha area. The predominant expression of isotypes IgG2 and IgG1 suggests a preferential Th1 like immune response. Anti-immunoserum stained just parasites and their particles, suggesting that a lot of from the immunostaining was non-specific. 1989; Islam 1991). Consequently, its been broadly reported how the isotype serum antibodies could be utilized as an sign for Th lymphocyte subset dominance (Finkelman 1990). Histopathological and immunocytochemical research demonstrating the great quantity of plasma cells and IgM, IgG and IgE antibodies complexed to antigens in the infiltrate of human and experimental lesions suggest that the humoral response might influence the elimination of the parasite ...
Figure 2 Homologous recombination into the murine Adk locus. (a) Restriction enzyme maps of the murine Adk wild-type allele, targeting vector pAdk-, and targeted allele. The thick lines indicate genomic sequences of the murine Adk gene homologous to the targeting vector. The thin lines in the wild type and targeted alleles indicate external Adk sequences not present in the targeting vector. In the wild-type sequence a checkered line marks the region with homology to mouse long interspersed nucleotide elements. Exon sequences, as well as the insertion cassette for the neomycin resistance gene (PGK-neo), are outlined as open boxes, loxP sites are outlined as vertical bars. PGK-neo is transcribed in the direction indicated by the arrow. The bicistronic expression cassette (hatched box) for the enhanced green fluorescent protein, the internal ribosomal entry site, and the tetracycline-dependent transactivator is fused in-frame to the Adk-specific exon, thus causing a disruption of the Adk gene. The ...
β-Cell proliferation is rare in both adults who are healthy and adults who have diabetes, and the molecular underpinnings of the natural resistance of β-cells to undergo mitosis are complex (5), difficult to study (6), and species dependent (7). Nonetheless, several small molecules have been reported to induce human β-cell proliferation (8-10), among them the adenosine kinase inhibitor 5-iodotubercidin (5-IT) (11). The latter compound was previously identified to promote β-cell and δ-cell proliferation in murine (and porcine) islets (12).. In this issue of Diabetes, Dirice et al. (8) convincingly demonstrate that 5-IT also stimulates human β-cell proliferation in vitro, as well as upon transplantation of human islets into mice in vivo. Notably, the authors report that this effect appears to be specific to endocrine pancreatic cells, in particular the β-cells (Fig. 1), and they did not find any increase in cell proliferation in several nonpancreatic tissues (8). Of significance, long-term ...
Adenosine (Ado) salvage is essential in plant development. The lack of Ado kinase activity (ADK) in Arabidopsis thaliana adk1 adk2 double mutants results in embryonic lethality; reduction of ADK expression causes a pleiotropic phenotype due to the accumulation of Ado inhibiting transmethylation activities. The phenotype of ADK mutants shows that this enzyme plays a critical role in Ado salvage but the functional significance of the other putative Ado recycling enzymes Ado deaminase (ADA) and Ado nucleosidase (ADN) in Arabidopsis thaliana have yet to be elucidated. ADA catalyzes the irreversible deamination of Ado to inosine. The locus At4g04880 (AtADA) of A. thaliana is annotated as encoding a putative ADA, based on its amino acid sequence similarity and the presence of important, conserved catalytic residues. However, indirect and direct spectrophotometric activity assays of the recombinant enzyme demonstrated that the gene product of this locus does not possess ADA activity; complementation ...
The aminopyrimidopyrimidine nucleoside 4-amino-8-(beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine (APP), which was previously shown to possess experimental antitumor and antiviral activity, was metabolized within WI-L2 human lymphoblastoid cells to a derivative identified as the beta-D-ribonucleotide (APP-MP). In a subline of WI-L2 cells deficient in adenosine kinase, this metabolite was not formed and APP was not cytotoxic, suggesting that APP is converted by adenosine kinase to its 5-monophosphate. Because no evidence of di- or triphosphates was seen, the monophosphate appeared to be the active species. Treatment of WI-L2 or L1210 cells with APP (10 microM) for 30 min caused extensive depletion of both purine and pyrimidine ribonucleotides. Purine and pyrimidine deoxyribonucleotides were also depleted. Cells were not protected from the cytotoxicity of APP by hypoxanthine plus uridine, but uridine plus adenosine plus 2-deoxycoformycin gave considerable protection. This result was ...
85] SNÁŠEL, J., P. NAUŠ, J. DOSTÁL, A. HNÍZDA, J. FANFRLÍK, J. BRYNDA, A. BOURDERIOUX, M. DUŠEK, H. DVOŘÁKOVÁ, J. STOLAŘÍKOVÁ, H. ZÁBRANSKÁ, R. POHL, P. KONEČNÝ, P. DŽUBÁK, I. VOTRUBA, M. HAJDÚCH, P. ŘEZÁČOVÁ, V. VEVERKA, M. HOCEK a I. PICHOVÁ. Structural Basis for Inhibition of Mycobacterial and Human Adenosine Kinase by 7-Substituted 7-(Het)aryl-7-deazaadenine Ribonucleosides. Journal of Medicinal Chemistry. 2014, 57 (20), 8268-8279. ISSN: 0022-2623. IF: 5.447. PMID: 25259627 ...
Sigma-Aldrich offers abstracts and full-text articles by [Denise E Fedele, Nicolette Gouder, Martin Güttinger, Laetitia Gabernet, Louis Scheurer, Thomas Rülicke, Florence Crestani, Detlev Boison].
Pu-erh tea is definitely believed to possess health benefits, the growth inhibition activity of Pu-erh tea about breast cancer cell offers not been investigated. P-JNK, P-p53 Tonabersat (Ser15), g21, CyclinD1 and CyclinE by Pu-erh tea remove. Our outcomes indicate that Pu-erh tea drinking water remove prevents cell expansion of MDA-MB-231 cells through the induction of […]. ...
For the biopharma industry investment, business development and competitive intelligence professionals who require information to support financing, partnering and licensing activities, BCIQ provides accurate information and context to support profitable and strategic decision making. Unlike other intelligence solutions, BCIQ exclusively supports the unique needs of the biopharma industry and provides in-depth, integrated analysis and context on clinical, strategic, financial, regulatory and policy issues.
Vanderpoorten A, Shaw AJ, Cox CJ. Evolution of multiple paralogous adenosine kinase genes in the moss genus Hygroamblystegium: phylogenetic implications. Molecular Phylogenetics and Evolution. 2004;31(2):505 - 516. doi:10.1016/j.ympev.2003.09.020 ...
Adenosine kinase (AK) is an enzyme responsible for converting endogenous adenosine (ADO) to adenosine monophosphate (AMP) in an adenosine triphosphate- (ATP-) dependent manner. The structure of AK consists of two domains, the first a large alpha/beta Rossmann-like nucleotide binding domain that forms the ATP binding site, and a smaller mixed alpha/beta domain, which, in combination with the larger domain, forms the ADO binding site and the site of phosphoryl transfer. AK inhibitors have been under investigation as antinociceptive, antiinflammatory, and anticonvulsant as well as antiinfective agents. In this work, we report the structures of AK in complex with two classes of inhibitors: the first, ADO-like, and the second, a novel alkynylpyrimidine series. The two classes of structures, which contain structurally similar substituents, reveal distinct binding modes in which the AK structure accommodates the inhibitor classes by a 30 degrees rotation of the small domain relative to the large ...
Bjursell MK, Blom HJ, Cayuela JA, Engvall ML, Lesko N, Balasubramaniam S,Brandberg G, Halldin M, Falkenberg M, Jakobs C, Smith D, Struys E, von Döbeln U, Gustafsson CM, Lundeberg J, Wedell A. Adenosine Kinase Deficiency Disrupts the Methionine Cycle and Causes Hypermethioninemia, Encephalopathy, and Abnormal Liver Function. Am J Hum Genet. 2011 Sep 28. PubMed PMID:21963049. Phenotype […]. ...
Masclaux-Daubresse C, Reisdorf-Cren M, Pageau K, Lelandais M, Grandjean O, Kronenberger J, Valadier MH, Feraud M, Jouglet T, Suzuki ...
Iodotubercidin is an adenosine kinase inhibitor that through its ability to increase levels of endogenous adenosine can enhance adenosines receptor-mediated effects. We investigated whether iodotubercidin can inhibit [3H]adenosine accumulation by inhibiting transport processes in addition to inhibition of intracellular trapping of labeled adenine nucleotides. 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. By using similar conditions, [3H]adenosine accumulation was significantly greater in Na+ buffer than in buffer containing N-methyl-D-glucamine in place of Na+; however, this effect may be explained by an observed 40% inhibition of adenosine kinase activity by N-methyl-D-glucamine. By using uptake intervals of 14 sec to ...
Intravenously administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. This process involves a specific transmembrane nucleoside carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical. 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. 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. Inosine formed by deamination of adenosine can leave the cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid. Adenosine monophosphate formed by phosphorylation of adenosine is incorporated into the high-energy phosphate pool. While extracellular adenosine is primarily cleared by cellular uptake with a ...
Study tour, meskipun itu artinya karya wisata atau belajar sambil jalan - jalan atau apalah gituu. Tapi menurut gue STUDY TOUR itu kayak travelling bareng temen sekolah seangkatan & bareng guru - guru. Meskipun siih biasanya disuruh nyimpulin atau buat makalah atau apalah gitu yang bertema tentang STUDY TOUR yang barusan dilakuin. STUDY TOUR itu sihh sebenernyaa asik banget, karna bisa seru - seruan bareng temen sekolah yang gokil abiss. Dan itu kamu pasti dapet uang saku buat beli oleh - oleh atau buat beli barang yg kamu perluin saat perjalanan STUDY TOUR. Sebelum STUDY TOUR itu biasanya beli barang - barang yang diperluin, dan biasanya hal itu tercapai, dan itu bahagiaa bgt rasanya. itu pendapat gue tentang "STUDY TOUR", kalo kamu gimana? ...
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Get the best price and selection of Open Box Large Diaphragm ADK Microphones Pro Audio at Musicians Friend. Many Open Box Large Diaphragm ADK Microphones Pro Audio are eligible for free shipping.
Bayangkan orang yang jadi marah kepada empunya mulut itu adalah isteri atau suami sendiri. Tentulah buah mulut itu akan menjadi punca perbalahan yang mungkin akan membawa kepada perpisahan. Katakanlah seorang suami (isteri) menceritakan kepada isterinya (suami) tentang adik-beradiknya yang membuat dia rasa tidak puas hati. Isteri (suami) pula menambah tokok untuk menampakkan lagi keburukan sifat adik beradik suami (isteri). Jangan disangka suami (isteri) itu bertambah benci kepada adik-beradiknya. Sebaliknya dia akan menjadi marah kepada isterinya (suaminya). Walaupun suami (isteri) tidak menyebutnya, tetapi dia akan mempertahankan adik beradiknya itu dalam hati. Kalau selalu terjadi begini, suami (isteri) akan bertambah baik kepada adik beradiknya tetapi benci pada isterinya (suaminya). Apa yang dikatakan dalam pepatah Melayu itu betul: Carik-carik bulu ayam, akhirnya bercantum juga ...
Protein sangat penting bagi tubuh. Ia mengandung unsur semacam C, O, H dan N yang tidak dipunyai oleh karbohidrat juga lemak. Karakter protein ini menjadikan ia khas. Selain itu, protein juga mengandung senyawa lain di antaranya belerang, fosfor bahkan ada pula yang menyimpan unsur logam semacam besi di setiap molekul-molekul penyusunnya. Mencermati kandungannya yang kompleks,…
Suatu pengatur yg sifatnya merekat secara otomatis mengendalikan temperatur dari bahan bakar minyak yg meninggalkan alat pemanas utk memelihara sifat perekatnya didlm.adapun batas dekat suatu permukaan adalah kekuatan yg lain,kekautan A disediakan pergerakan lapisan pelindung.kekuatan ini disebut friksi.selalu berlawanan dgn gerakan itu.gerakan yg berlawanan itu ada ditiap mesin.peristiwa itu dpt dikurangi oleh pemberian minyak lumas tetapi tdk perna dgn sepenuhnya dipindahkan dlm mengangsur permukaan yg lain dibanding setelah pergerakan itu dimulai.kekuatan yg sedikit lebih besar ini disebut friksi yg statis.kekuatan yg harus digunakan utk memelihara satu permukaan yg lain. ...
Arti dan makna apa itu pangajeng- ajeng adalah dalam istilah Sansekerta. Kamus, arti dan daftar istilah Sansekerta lengkap dari berbagai sumber terpercaya.
Arti dan makna apa itu MIGRASI ULANG- ALIK adalah dalam istilah Kependudukan. Kamus, arti dan daftar istilah Kependudukan lengkap dari berbagai sumber terpercaya.
Walau bagaimanapun, lama-kelamaan persepsi saya berubah. Ya, pasti ramai yang akan mengatakan sebabnya kerana memang dunia itu yang perlu saya gelumang, kalau tidak pasti tidak lulus dalam peperiksaan. Hakikatnya, bukan. Saya mula ingin menyelongkar dunia politik ini apabila kebanyakkan pensyarah saya tidak sahaja bersyarah di hadapan. Sebaliknya sentiasa memberi peluang kepada kami untuk menyuarakan pendapat. Bermula daripada situ, saya belajar berfikir dan menilai sendiri. Pemikiran saya lebih terbuka dan menjadikan saya neutral. Neutral bukan beerti lalang ya kawan-kawan. Pendirian saya adalah saya tidak mahu memihak mana-mana belah pihak sedangkan setiap daripadanya mempunyai agenda yang tersendiri ...
Recombinant fragment, corresponding to amino acids 22-362 of Human ADK with N terminal His tag, 362 amino acids with tag, MWt 40.5kDa.
Kadang istilah manusiawi menjadi pengecualian sendiri terhadap sebuah kesalahan. Contoh seperti yang ada di gambar ini yaitu ada seseorang yang menguap karena mengantuk/bosan. Itu tidak apa-apa karena itu manusiawi. Tapi bukankah seorang prajurit seharusnya selalu sigap dan terjaga? Bagaiaman jika musuh datang saat kondirinya tidak sigap? Ah, tapi tidak apa-apa, toh namanya manusia dan mengantuk itu manusiawi ...
Pada 2015, jumlah dagangan dua hala Malaysia-Iran susut kepada AS$700 juta berbanding tahun sebelumnya berikutan pelaksanaan sekatan antarabangsa ke atas negara itu. Selepas sekatan itu ditamatkan, jumlah dagangan dua hala itu melonjak 22.7 peratus kepada RM1.32 bilion pada tujuh bulan pertama tahun ini berbanding RM1.07 bilion bagi tempoh sama, tahun lalu ...
Sabar...sabar dik.Adik Fatihah kena faham tujuan adik diciptakan di dunia bukanlah semata-mata untuk melaram melawa bergaya cantik jelita.Malah perbuatan adik itu hanya menambahkan kemungkaran sahaja.Jika adik percaya bahawa diri adik diciptakan semata-mata jadi penyeri sahaja,maka samalah adik macam pokok bunga plastik.Jadi penyeri sahaja.Tidak lebih dari itu.Tahukah adik,adik diciptakan di dunia semata-mata untuk buat satu PERKARA MULIA.Adik diciptakan bukan jadi penyeri malah bertambah-tambah lebih mulia dari itu.Untuk buat satu PERKARA MULIA.Itulah beza penciptaan adik dengan pokok bunga plastik.Penciptaan pokok bunga plastik hanyalah sebagai penyeri sahaja.Tetapi PENCIPTAAN DIRI ADIK ADALAH UNTUK BUAT TUGAS MULIA.Gunung-ganang,kambing,awan,bintang,matahari,planet-planet pun tidak dapat buat TUGAS MULIA INI tau. ...
Oh, jadi ternyata tujuan akhir PKMP itu menghasilkan research paper yang nantinya akan dipresentasikan di forum ilmiah. Okay, next years challenge will be accepted. Kan, seenggaknya kalo para dosen itu bilang dari awal, kita akan menyesuaikan dengan tema-tema konferensi tertentu tahun depan; jadi penemuan tema dan lingkup penelitian juga akan lebih mudah. Hanya saja, penelitian itu…
Pilihan Forex semakin popular di kalangan pedagang kerana jenis dagangan ini boleh menghasilkan keuntungan tanpa had. Selain itu, prinsip-prinsip perdagangan agak mudah dan mudah difahami walaupun oleh pemula. Memilih dari pilihan urusniaga harian, tamat tempoh, dan pilihan binari, spekulator boleh menjual sebarang aset dari mata wang dan logam kepada saham syarikat terkenal. Pelaburan pilihan akan membuat keuntungan sekiranya keadaan kontrak itu dipenuhi. Dengan kata lain, seorang pedagang perlu meramalkan sama ada harga pengaktifan akan sama atau lebih tinggi atau lebih rendah daripada harga penutupan.. ...
Berdengkur ialah bunyi bising semasa bernafas, di mana sebahagian daripada saluran pernafasan atas seseorang itu tersumbat. Ia berlaku apabila terdapat sekatan pada aliran udara di dalam saluran pernafasan di bahagian belakang mulut dan hidung. Bunyi itu dikeluarkan apabila tisu di bahagian atas saluran pernafasan bergesel dan bergetar di antara satu sama lain. Berdengkur bertambah kerap mengikut umur dan biasanya tidak membahayakan. ...
Dalam Rm 1800 juga termasuk sepasang baju lace perempuan (Design pilihan hati) dan juga baju untuk lelaki untuk dimiliki terus!!di ulang taip..DIMILIKI terus!! Cakap pasal design pilihan hati..bermakna..Anda beli majalah pengantin,kalau anda berkenan dgn mana2 design dlm majalah itu,sile bawa design itu ke butik tersebut. dan dia akan design baju anda mengikut design tersebut..sekian~ *faham tak?* ayat berbelit sampai kpl sy dh terbelit2..I was like "Serius ke??"..and dia kata "Serius cik"..OOHH suke ...
Ketua Pegawai Operasi (Bahagian Tenusu), Tony Lee, bagaimanapun berkata kumpulan itu belum membuat keputusan bila semakan kenaikan harga itu akan berkuat kuasa ...
Sekiranya melalui ujian ultrasound mendapati tiada janin di dalam kandungan, ujian air kencing juga perlu dilakukan. Kebiasaannya dalam ujian air kencing mendapati hormon BHCG meningkat dalam darah. Keadaan sedemikian perlu diawasi kerana risiko terdekat ialah pendarahan paling banyak dan melimpah boleh mengancam nyawa. ...
walaupun pertunangan ni berlaku secara tiba-tiba (ketika itu), namun ia sangat membawa makna kepada hubungan kami.. semoga ikatan ini akan terus kekal hingga ke jinjang pelamin..insyaAllah ...
KETIKA itu saya lihat Kylee tidak sedarkan diri, tidak bernafas lagi, lantas saya menarik Kylee keluar dari tab mandi dan terus memberikan bantuan CPR (pernafas
terlalu banyak keluar masuk pelajar dan CM terpaksa menaip senarai nama berhelai-helai... itu kerja biasa setiap hujung bulan ...
Wymieszaj w jednej misce przesianą mąkę, cukier i proszek do pieczenia, a w drugiej połącz roztopione masło z mlekiem i jajkiem. Następnie wymieszaj zawartości obu misek (nie musi być na gładką masę), dodaj pokrojoną drobno czekoladę i pokrojone gruszki. Wymieszaj. Nałóż do papilotek i formy. Muffiny piecz przez 20-25 minut, we wcześniej rozgrzanym piekarniku do 200 stopni C ...
Objective Fatty acid oxidation in macrophages is thought to regulate inflammatory status and insulin-sensitivity. fatty acids and are required for fatty acid oxidation [13]. Carnitine O-octanoyltransferase (CrOT) and carnitine acetyltransferase (CrAT) conjugate medium-chain and short-chain acyl-CoA to carnitine, respectively [13]. CrAT is localized primarily within the mitochondrial matrix and catalyzes both the addition and the removal of carnitine from acetyl-CoA [14], facilitating the efflux of mitochondrial acetyl-CoA and buffering the intracellular pools of acetyl-CoA and carnitine. Consistent with an important role of fatty acid oxidation in macrophages, CPT1, CPT2, Crat and Crot are abundantly expressed in macrophages [15]. Interestingly, the CrAT activity is reduced during obesity and aging, leading to impaired glycemic control [16], [17]. Notably, muscle-specific deletion of CrAT was shown to reduce exercise performance [18] and exacerbated metabolic dysregulation in HFD mice [19]. ...
Animal models of epilepsy. For seizure threshold testing, male CD-1 mice (25-35 g) were used. 0.75% (w/v) PTZ was prepared in isotonic saline. 5-Aza-2dC was prepared in isotonic saline and administered via tail vein 10 minutes prior to initiation of PTZ infusion. PTZ was infused via tail vein at a rate of 0.2 ml/min using a Hamilton microsyringe (Harvard Apparatus) in freely moving animals. Times to first twitch, first clonus, and final extensor phase were recorded. Infusion was stopped after a final extension or at a maximum volume of 0.9 ml, whichever came first.. For the kindling model and associated 5-Aza-2dC drug testing, male Sprague Dawley rats (300-350 g) were implanted with bipolar, coated stainless steel electrodes (0.20 mm in diameter; Plastics One) into the right hippocampus (stereotactic coordinates relative to Bregma: AP, -4.2 mm; ML, -4.6; DV, -5.6). For experiment 1, the animals were kindled based on a rapid kindling protocol (43). Briefly, using a Grass S-88 stimulator, rats ...
Adenosine is a candidate sleep substance. It can be both a distress signal of importance in pathology and a physiological regulator. Key factors in determining which of these possibilities pertain are: (i) the number of receptors expressed, and (ii) the mechanisms that establish extracellular adenosine levels. The roles of adenosine are studied by means of antagonists and/or animals (mostly mice) with targeted deletions of receptors or enzymes involved in adenosine metabolism. Whereas adaptive changes in the genetically modified mice can occur for the physiologically important effects, such adaptive changes are less likely to occur in situations where adenosine acts as a distress signal. The relevance to sleep will be covered only in general terms in this review and will be covered in other contributions to this volume.
Banyak yang mengatakan kalo bore up itu meningkatkan tenaga, sedangkan Stroke up mendongkrak torsi. Mesin Bore up mengejar top speed, Stroke up memburu akselerasi. Bore up atasnya badai, bawahnya mlempem. Stroke up kebalikannya; bawahnya galak, atasnya melempem. Hmmmm….benarkah begitu? entahlah, tapi menurut saya sih gak hitam putih kayak gitu juga. Kebetulan satria fu saya pernah bore up dengan stroke standar, lalu pernah juga ngalamin Stroke up dengan piston standar (tanpa bore up). Tenaga dan torsi ya bertambah dua-duanya akibat naiknya kapasitas silinder (cc), baik itu dengan bore up maupun stroke up.. Beberapa tahun lalu, jurus stroke up memang masih terbilang kurang populer diterapkan di FU. Yang booming itu bore up dengan piston tiger atau scorpio. FUers lebih memilih bore up dengan alasan bore up lebih aman, lebih mudah diaplikasi, lebih kuat bermain rpm tinggi, lebih awet, lebih tinggi top speednya, dan banyak pertimbangan lainnya. Tapi sekarang, trendnya mulai berubah. Owner Satria ...
Medzinárodná telekomunikačná únia (International Telecommunication Union, ITU) so sídlom v Ženeve je najstaršia odborná organizácia pridružená k OSN.. Význam ITU postupne rástol s rozširujúcim sa sortimentom telekomunikačných služieb a sietí. V roku 1947 sa ITU po vzniku OSN stala jednou z jej špecializovaných agentúr. Formálne je ITU medzivládnou organizáciou. Každý suverénny štát, ktorý je členom OSN, môže byť i členom ITU. ITU má dnes unikátnu organizačnú štruktúru: generálny sekretár ITU je iba legislatívnym zástupcom organizácie, výkonnú moc majú riaditelia troch sektorov - rádiokomunikácií, telekomunikácií a rozvoja.. Sídlo únie je od roku 1948 v Ženeve, kam sa presťahovalo z Bernu.. ...
Get the best price and selection of New Studio Recording Multi-pattern Large Diaphragm ADK Microphones Pro Audio at Musicians Friend. Many New Studio Recording Multi-pattern Large Diaphragm ADK...
Ya Allah, bahawasanya waktu Dhuha itu waktu Dhuha-Mu, Kecantikan ialah kecantikan-Mu, Keindahan itu keindahan-Mu, Kekuatan itu kekuatan-Mu, Kekuasaan itu kekuasaan-Mu, dan Perlindungan itu perlindungan-Mu. Ya Allah, jika rezekiku masih di langit, turunkanlah dan jika ada di dalam bumi, keluarkanlah, jika sukar permudahkanlah, jika haram sucikanlah, jika masih jauh dekatkanlah waktu Dhuha-Mu keagungan-Mu, keindahan-Mu, kekuatan-Mu dan kekuasaan-Mu, Limpahkanlah kepada kami segala yang telah Engkau limpahkan kepada hamba-hamba-Mu yang soleh." Amin ...
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. ...
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Here we report that adenosine induces SphK1 activity in human and mouse sickle and normal erythrocytes in vitro. (nih.gov)
  • Moreover, in vitro data suggest the existence of an additional layer of modulatory crosstalk between the astrocyte-based adenosine cycle and inflammation. (uva.nl)
  • 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)
  • 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)
  • 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)
  • 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)