Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.5.4.4 (adenosine deaminase)
5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene loci for S-adenosylhomocysteine hydrolase ( AHCY ) and adenosine deaminase (ADA), two enzymes with related metabolic functions, have both been assigned to human chromosome 20. We have used rodent-human somatic hybrids containing translocations involving human chromosome 20 to more precisely determine the relative locations of the AHCY and ADA loci. Our results assign the AHCY locus to the long arm of chromosome 20, in the region cen---- q131 , and ADA to the region q131 ----qter.
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PMID:Regional localization of the human genes for S-adenosylhomocysteine hydrolase (cen----q131) and adenosine deaminase (q131----qter) on chromosome 20. 658 34

Mice were given constant infusions of the adenosine deaminase inhibitor, 2'-deoxycoformycin, by i.p. implantation of microosmotic pumps, delivering the compound at a rate of 0.16 mg hr-1 kg-1. In accordance with published data, we observed that adenosine deaminase in most tissues was nearly completely inhibited. In addition, the S-adenosylhomocysteine hydrolase activity decreased slowly and showed a half-life in liver of about 4 hr. The rate and extent of the inactivation were highest in spleen. The amounts of adenosine, 2'-deoxyadenosine, S-adenosylhomocysteine, and S-adenosylmethionine were determined in treated animals and control animals. The tissue levels of adenosine and, to a lesser degree, S-adenosylhomocysteine and S-adenosylmethionine were critically dependent on the procedure used for processing the tissues. Lowest concentrations were observed when the organs were frozen in situ by liquid nitrogen. Treatment with 2'-deoxycoformycin induced no or a moderate increase in tissue content of adenosine and S-adenosylhomocysteine, whereas the amount of 2'-deoxyadenosine increased markedly, especially in spleen and thymus. 2'-Deoxycoformycin treatment caused an increase in adenosine and 2'-deoxyadenosine, but not S-adenosylhomocysteine, in serum of mice.
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PMID:Effect of 2'-deoxycoformycin infusion on S-adenosylhomocysteine hydrolase and the amount of S-adenosylhomocysteine and related compounds in tissues of mice. 660 64

The inhibition of S-adenosylhomocysteine hydrolase and accumulation of dATP in thymus, spleen and other tissues of mice treated with the adenosine deaminase inhibitor coformycin were studied in parallel with the competence of thymocytes and spleen leucocytes to undergo mitogen-induced transformation. Newborn mice were lethally sensitive to daily injections of coformycin, 0.2 mg/kg, whereas adult mice were not. Developmental profiles of enzymes of nucleoside metabolism showed adenosine deaminase and purine nucleoside phosphorylase to be greatest in thymus around day 20 and to decrease for animals older than 60 days. The most notable change was a 3-fold increase in spleen leucocyte adenosine deaminase activity between days 10 and 30. Adenosine deaminase activity was reduced to less than 10% of normal in tissues of newborns treated with coformycin for 12-14 days. S-Adenosylhomocysteine hydrolase was also reduced to 5-40% of normal with no evidence of tissue specificity. Both thymocytes and erythrocytes of coformycin-treated mice accumulated dATP whereas spleen leucocytes did not. For coformycin-treated mice, spleen leucocyte and thymocyte response to concanavalin A (Con A) was reduced to 20 and 60% of controls respectively. Coformycin, 3.6 microM, also potentiated the in vitro toxicity of adenosine and deoxyadenosine toward thymocytes or spleen leucocytes by approximately an order of magnitude. Our observations are consistent with dATP being involved in impairment of thymocyte responsiveness; however, it appears unlikely that either dATP elevation or S-adenosylhomocysteine hydrolase inhibition is involved in the mechanism of impairment of spleen leucocyte response by coformycin.
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PMID:S-adenosylhomocysteine hydrolase activity, deoxyadenosine triphosphate accumulation, and competence of thymocyte and spleen leucocyte response to mitogens in coformycin-treated mice. 686 Mar 59

S-Adenosylhomocysteine hydrolase activity decreased in vitro time-dependently in liver homogenates obtained from rats treated in vivo with erythro-9-(2-hydroxynon-3-yl)adenine, a potent inhibitor of adenosine deaminase. The inhibitor in itself had no effect on the stability of the hydrolase. The inactivation of S-adenosylhomocysteine hydrolase was irreversible, proceeded fairly rapidly at a low temperature (0 degrees C) and showed first-order reaction kinetics. Adenosine was found to accumulate in these tissue homogenates during storage. Several lines of evidence suggest that adenosine caused the observed suicide-like inactivation post mortem. Pre-incubation of purified S-adenosylhomocysteine hydrolase at 0 degrees C with adenosine showed a half-maximal inactivation rate at 33 microM substrate concentration; the rate constant of inactivation was 0.01 min-1. Inactivation during tissue preparation and storage complicates the assay of S-adenosylhomocysteine hydrolase activity in samples that contain an inhibitor of adenosine deaminase. These results also suggest that the decrease of S-adenosylhomocysteine hydrolase activity reported to occur in several disturbances of purine metabolism should be re-examined to exclude the possibility of inactivation of the enzyme in vitro.
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PMID:Inactivation of liver S-adenosylhomocysteine hydrolase in vitro of rats treated with erythro-9-(2-hydroxynon-3-yl)adenine. 698 48

Human-Chinese hamster cell hybrids and a monoclonal antibody to human S-adenosylhomocysteine hydrolase were used to identify chromosome 20 as the location of the human gene for this enzyme. The gene for adenosine deaminase had previously been mapped to this chromosome. The activity of S-adenosylhomocysteine hydrolase is dependent in vivo on that of adenosine deaminase, since the substrates for the deaminase, adenosine and deoxyadenosine, respectively, inhibit and inactivate S-adenosylhomocysteine hydrolase in genetic or drug-induced adenosine deaminase deficiency. This functional dependence and the likelihood that S-adenosylhomocysteine hydrolase, a eukaryotic enzyme, arose later than adenosine deaminase, which occurs in prokaryotes as well as eukaryotes, suggest that the occurrence of their genes on the same chromosome may have evolutionary significance. In addition, the unusual capacity of S-adenosylhomocysteine hydrolase to form stable complexes with adenosine and its cofactor, nicotinamide adenine dinucleotide, suggest that evolution of its gene may have involved recombination of a portion of the adenosine deaminase gene with an adenine nucleotide domain-coding sequence of another preexisting gene.
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PMID:The human genes for S-adenosylhomocysteine hydrolase and adenosine deaminase are syntenic on chromosome 20. 707 34

The present review describes the biological implications of the periodic changes of adenosine concentrations in different tissues of the rat. Adenosine is a purine molecule that could have been formed in the prebiotic chemical evolution and has been preserved. The rhythmicity of this molecule, as well as its metabolism and even the presence of specific receptors, suggests a regulatory role in eukaryotic cells and in multicellular organisms. Adenosine may be considered a chemical messenger and its action could take place at the level of the same cell (autocrine), the same tissue (paracrine), or on separate organs (endocrine). Exploration of the circadian variations of adenosine was planned considering the liver as an important tissue for purine formation, the blood as a vehicle among tissues, and the brain as the possible acceptor for hepatic adenosine or its metabolites. The rats used in these studies were adapted to a dark-light cycle of 12 h with an unrestrained feeding and drinking schedule. The metabolic control of adenosine concentration in the different tissues studied through the 24-h cycle is related to the activity of adenosine-metabolizing enzyme: 5'-nucleotidase adenosine deaminase, adenosine kinase, and S-adenosylhomocysteine hydrolase. Some possibilities of the factors modulating the activity of these enzymes are commented upon. The multiphysiological action of adenosine could be mediated by several actions: (i) by interaction with extracellular and intracellular receptors and (ii) through its metabolism modulating the methylation pathway, possibly inducing physiological lipoperoxidation, or participating in the energetic homeostasis of the cell. The physiological meaning of the circadian variations of adenosine and its metabolism was focused on: maintenance of the energetic homeostasis of the tissues, modulation of membrane structure and function, regulation of fasting and feeding metabolic pattern, and its participation in the sleep-wake cycle. From these considerations, we suggest that adenosine could be a molecular oscillator involved in the circadian pattern of biological activity in the rat.
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PMID:Circadian variations of adenosine and of its metabolism. Could adenosine be a molecular oscillator for circadian rhythms? 764 13

We report the generation and characterization of mice lacking adenosine deaminase (ADA). In humans, absence of ADA causes severe combined immunodeficiency. In contrast, ADA-deficient mice die perinatally with marked liver-cell degeneration, but lack abnormalities in the thymus. The ADA substrates, adenosine and deoxyadenosine, are increased in ADA-deficient mice. Adenine deoxyribonucleotides are only modestly elevated, whereas S-adenosylhomocysteine hydrolase activity is reduced more than 85%. Consequently, the ratio of S-adenosylhomocysteine (AdoMet) to S-adenosyl homocysteine (AdoHcy) is reduced threefold in liver. We conclude that ADA plays a more critical role in murine than human fetal development. The murine liver pathology may be due to AdoHcy-mediated inhibition of AdoMet-dependent transmethylation reactions.
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PMID:Adenosine-deaminase-deficient mice die perinatally and exhibit liver-cell degeneration, atelectasis and small intestinal cell death. 767 Apr 65

Endogenous adenosine in the extracellular space inhibits neuronal activity. The roles of adenosine kinase, S-adenosylhomocysteine-hydrolase and adenosine deaminase activities in the regulation of the adenosine levels were investigated in rat hippocampal slices. Iodotubercidin, an inhibitor of adenosine kinase, added to the perfusion fluid at 5 microM increased the release of adenosine from the slices more than 2-fold. Iodotubercidin treatment caused inhibition of population spike discharges and hyperpolarization of pyramidal cells, mimicking the effects of exogenously applied adenosine. Adenosine dialdehyde, an inhibitor of S-adenosylhomocysteine hydrolase, and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), an inhibitor of adenosine deaminase had little or no effect on the parameters tested. The action of iodotubercidin was greater during deaminase inhibition. The A1-receptor antagonist DPCPX had actions opposite to those of adenosine and blocked the electrophysiological effects of exogenous adenosine and of iodotubercidin. Thus adenosine kinase activity is a significant factor in the regulation of adenosine levels in the hippocampus.
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PMID:Inhibition of adenosine kinase increases endogenous adenosine and depresses neuronal activity in hippocampal slices. 783 17

Evaluation of enzyme activities involved in nucleotide metabolism and adenosine production within different cell types can provide important information on their contribution to the overall metabolism of the heart. The following enzyme activities were determined: adenosine kinase (AK), adenosine deaminase (ADA), S-adenosylhomocysteine hydrolase (SAHH), purine nucleoside phosphorylase (PNP), AMP deaminase (AMPD), membrane 5'nucleotidase (M5'N), AMP specific (AC5'N) and IMP specific (IC5'N) cytosolic 5'nucleotidases in (1) rat heart (n = 5), (2) rat cardiomyocytes obtained by collagenase digestion (n = 5), (3) human heart (n = 6) obtained from explants or papillary muscles collected during heart transplantation or mitral valve replacement, and (4) human umbilical cord endothelial cells in primary culture (n = 4). In the human heart, activities (mumol/min/g wet weight) were as follows: AK (0.14 +/- 0.01), ADA (0.46 +/- 0.03), SAHH (0.001 +/- 0.0003), PNP (0.43 +/- 0.08), AMPD (0.41 +/- 0.05), M5'N (1.75 +/- 0.12), IC5'N (0.21 +/- 0.03) and AC5'N (0.11 +/- 0.02). These enzyme activities were lower than those determined in the rat heart with the exception of AC5'N and IC5'N which were equal. The most prominent difference observed was for AMPD and M5'N which were nine and five-fold more active in the rat heart. Rat cardiomyocyte enzyme activities were comparable to those measured in whole rat heart with the exception of ADA (six-fold lower) and PNP (16-fold lower). Endothelial cell activities were notably different from those in the human heart particularly in the case of SAHH (nine-fold higher) and PNP (16-fold higher).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nucleotide and adenosine metabolism in different cell types of human and rat heart. 789 72

Previous studies showed that in cultured chick ciliary ganglion neurons and CNS glia, adenosine can be synthesized by hydrolysis of 5'-AMP and that the accumulation of the adenosine degradative products inosine and hypoxanthine was significantly greater in glial than in neuronal cultures. Furthermore, previous immunochemical and histochemical studies in brain showed that adenosine deaminase and nucleoside phosphorylase are localized in endothelial and glial cells but are absent in neurons; however, adenosine deaminase may be found in a few neurons in discrete brain regions. These results suggested that adenosine degradative pathways may be more active in glia. Thus, we have determined if there is a differential distribution of adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase enzyme fluxes in glia, comparing primary cultures of central and ciliary ganglion neurons and glial cells from chick embryos. Hypoxanthine-guanine phosphoribosyltransferase and production of adenosine by S-adenosylhomocysteine hydrolase activity were also examined. Our results show that there is a distinct profile of purine metabolizing enzymes for glia and neurons in culture. Both cell types have an S-adenosylhomocysteine hydrolase, but it was more active in neurons than in glia. In contrast, in glia the enzymatic activities of xanthine oxidase (443 +/- 61 pmol/min/10(7) cells), nucleoside phosphorylase (187 +/- 8 pmol/min/10(7) cells), and adenosine deaminase (233 +/- 32 pmol/min/10(7) cells) were more active at least 100, 20, and five times, respectively, than in ciliary ganglion neurons and 100, 100, and nine times, respectively, than in central neurons.
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PMID:Differential distribution of purine metabolizing enzymes between glia and neurons. 811 1


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