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:3.1.3.5 (5'-nucleotidase)
3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of adenosine on the metabolism of prelabeled adenine nucleotides was investigated in isolated hepatocytes. Adenosine caused an approximately equal to 2-fold increase in the ATP content of the cells. This effect was in part counteracted by an increased rate of adenine nucleotide catabolism that could be explained by a stimulation of both AMP deaminase (AMP aminohydrolase, EC 3.5.4.6) and the cytoplasmic 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) because of the increased concentration of ATP. The unexpected finding that labeled adenosine was formed immediately after the addition of the unlabeled nucleoside could be explained by the trapping effect of adenosine. An accumulation of labeled adenosine was observed also in the presence of 5-iodotubercidin, a potent inhibitor of adenosine kinase (ATP:adenosine 5'-phosphotransferase, EC 2.7.1.20). Under these conditions, there was a decrease in the concentration of ATP in the cell and a 2- to 3-fold increase in the rate of formation of allantoin. This formation of adenosine was only slightly decreased by inhibition of the membranous 5'-nucleotidase; it led to the accumulation of S-adenosylhomocysteine in the presence of coformycin and an excess of L-homocysteine. It was concluded that, under basal conditions, the cytoplasmic 5'-nucleotidase present in the liver cell continuously produces adenosine, which is immediately reconverted into AMP by adenosine kinase, without giving rise to allantoin. This futile cycle between AMP and adenosine amounts to at least 20 nmol/min per g of liver and, thus, exceeds the basic rate of allantoin formation.
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PMID:Evidence for a substrate cycle between AMP and adenosine in isolated hepatocytes. 630 84

Primary rat cardiomyocyte cultures were utilized as a model for the study of purine nucleotide metabolism in the heart muscle, especially in connection with the mechanisms operating for the conservation of adenine nucleotides. The cultures exhibited capacity to produce purine nucleotides from nonpurine molecules (de novo synthesis), as well as from preformed purines (salvage synthesis). The conversion of adenosine to AMP, catalyzed by adenosine kinase, appears to be the most important physiological salvage pathway of adenine nucleotide synthesis in the cardiomyocytes. The study of the metabolic fate of IMP formed from [14C]formate or [14C]hypoxanthine and that of AMP formed from [14C]adenine or [14C]adenosine revealed that in the cardiomyocyte the main flow in the nucleotide interconversion pathways is from IMP to AMP, whereas the flux from AMP to IMP appeared to be markedly slower. Following synthesis from labeled precursors by either de novo or salvage pathways, most of the radioactivity in purine nucleotides accumulated in adenine nucleotides, and only a small proportion of it resided in IMP. The results suggest that the main pathway of AMP degradation in the cardiomyocyte proceeds through adenosine rather than through IMP. About 90% of the total radioactivity in purines effluxed from the cells during de novo synthesis from [14C]formate or following prelabeling of adenine nucleotides with [14C]adenine were found to reside in hypoxanthine. The activities in cell extracts of AMP 5'-nucleotidase and IMP 5'-nucleotidase, which catalyze nucleotide degradation, and of AMP deaminase, a key enzyme in the purine nucleotide cycle, were low. The nucleotidase activity resembles, and that of the AMP deaminase contrasts the respective enzyme activities in extracts of cultured skeletal-muscle myotubes. The results indicate that in the cardiomyocyte, in contrast to the myotube, the main mechanism operating for conservation of nucleotides is prompt phosphorylation of AMP, rather than operation of the purine nucleotide cycle. The primary cardiomyocyte cultures are a plausible model for the study of purine nucleotide metabolism in the heart muscle.
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PMID:Characterization of purine nucleotide metabolism in primary rat cardiomyocyte cultures. 632 48

Some purine metabolizing enzymes of lymphocytes and granulocytes were determined in 13 patients with cirrhosis of the liver and in a control group consisting of 18 healthy blood donors. Furthermore cytidine deaminase (EC 3, 5, 4, 5) (CRD) activity was determined in the granulocytes of these patients and in 16 controls. An increase of adenosine deaminase (EC 3, 5, 4, 4) (ADA) activity was found in granulocytes (P less than 0.01) as well as in lymphocytes (P less than 0.01) of the cirrhotic patients as compared to controls. Purine nucleoside phosphorylase (EC 2, 4, 2, 1) (PNP) activity in granulocytes and lymphocytes was identical in the two groups. In lymphocytes of cirrhotic patients decreased hypoxanthine guanine phosphoribosyltransferase (EC 2, 4, 2, 8) (HGPRT) (P less than 0.01), adenine phosphoribosyltransferase (EC 2, 4, 2, 7) (APRT) (P less than 0.02) and adenosine kinase activities (EC 2, 7, 1, 20) (AK) (P less than 0.05) were demonstrated. 5'-nucleotidase (5'-N (EC 3, 1, 3, 5) activity in lymphocytes of cirrhotic patients was slightly increased, the increase being correlated to the level of serum gamma globulin. Granulocytes from cirrhotic patients showed a decrease of CRD (P less than 0.05). The finding that ADA activity is increased in mature lymphocytes and granulocytes from cirrhotic patients argues against the possibility that increase of lymphocytes ADA activity is a consequence of malignant transformation or immaturity.
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PMID:Changes in some nucleoside metabolizing enzymes of lymphocytes and granulocytes from patients with cirrhosis of the liver. 641 76

Adenosine kinase, adenosine deaminase, hypoxanthine phosphoribosyltransferase, inosine-nucleoside phosphorylase, 5'-AMP deaminase and 5'-IMP nucleotidase were identified in cell-free extracts of duckling erythrocytes; no evidence for 5'-AMP nucleotidase and xanthine oxidase activity was found. The Km values for the duckling red cell enzymes were similar to those reported for human erythrocytes. Plasmodium lophurae extracts demonstrated similar enzyme activities except for 5'-AMP deaminase and 5'-IMP nucleotidase which were absent. It is proposed that during infection erythrocytic AMP is catabolized to IMP, inosine and hypoxanthine; the hypoxanthine is taken up by the plasmodium, utilized to form IMP, and this in turn is converted into adenine and guanine nucleotides.
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PMID:Purine metabolizing enzymes of Plasmodium lophurae and its host cell, the duckling (Anas domesticus) erythrocyte. 678 22

Adenosine triphosphate metabolism in caudal epididymis bovine spermatozoa was studied. Measurements by HPLC at appropriate time intervals of the spermatozoa content of ATP and its derivatives were carried out under different experimental conditions. In the presence of 2-D-glucose, cellular ATP was transformed almost quantitatively into ADP and AMP at a rate of 2.3 nmol/min per 10(8) cells. At the same time, ADP and AMP accumulated at a rate of 1.52 and 0.58 nmol/min per 10(8) cells, respectively. In the first 4 min, about 50% of total ATP was degraded, the AEC of the cells dropped to non-physiological values while the content of other nucleosides did not vary significantly. Inorganic P(i) content also remained unchanged. Under non-induced conditions up to 240 min, no variations of the adenylic content and of the EC value was observed. Under induced and non-induced conditions, IMP and adenosine were not detected within the spermatozoa. The lack of IMP might be ascribed either to the absence of AMP deaminase, whose activity has never been found in the spermatozoa or to the intracellular environment which down regulates the activity of the enzyme. In order to explain low levels and absence of variations of adenosine, several enzymic investigations were carried out. Adenosine kinase activity was not determined, therefore the transformation of adenosine into AMP had to be excluded. Nevertheless, enzymic activities potentially able to dephosphorylate the formed AMP are present in the spermatozoa. Our findings are indicative of the existence in the spermatozoa of acid and alkaline phosphatase and of 5'-nucleotidase membrane-derived.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine triphosphate catabolism in bovine spermatozoa. 758 34

Hyperthyroidism induces a number of metabolic and physiological changes in the heart including hypertrophy, increase in inotropic status, and alterations of myocardial energy metabolism. The effects of hyperthyroidism on adenosine metabolism which is intimately involved in the control of many aspects of myocardial energetics, have not been clarified. The aim of this study was thus to evaluate the potential role of adenosine in the altered physiology of the hyperthyroid heart. Transport of adenosine was studied in cardiomyocytes isolated from hyperthyroid and euthyroid rats. Activities of different enzymes of purine metabolism were studied in heart homogenates and concentrations of nucleotide and creatine metabolites were determined in hearts freeze-clamped in situ. Both transport of adenosine into cardiomyocytes and the rate of intracellular phosphorylation were higher in the hyperthyroid rat. At 10 microM concentration, adenosine transport rates were 275 and 197 pmol/min/mg protein in hyperthyroid and euthyroid cardiomyocytes respectively whilst rates of adenosine phosphorylation were 250 and 180 pmol/min/mg prot. An even more pronounced difference was observed if values were expressed per number of cells due to cardiomyocyte enlargement. Hyperthyroidism was associated with a 20% increase in adenosine kinase, 30% decrease in membrane 5'-nucleotidase and 15% decrease in adenosine deaminase activities measured in heart homogenates. In addition there was a substantial depletion in the total creatine pool from 63.7 to 41.6 mumol/g dry wt, a small decrease in the adenylate pool (from 27.2 to 24.3 mumol/g dry wt) and an elevation of the guanylate pool (from 1.22 to 1.36). These results show that adenosine transport and phosphorylation capacity is enhanced in hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperthyroidism increases adenosine transport and metabolism in the rat heart. 759 49

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

EICAR (5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide) is a cytostatic agent that inhibits murine leukemia L1210 and human lymphocyte CEM cells at a 50% inhibitory concentration of 0.80-1.4 microM, respectively. EICAR causes a rapid and marked inhibition of inosinate (IMP) dehydrogenase (EC 1.1.1.205) activity in intact L1210 and CEM cells reflected by a concentration-dependent accumulation of IMP and depletion of GTP and dGTP levels. EICAR 5'-monophosphate is a potent inhibitor of purified L1210 cell IMP dehydrogenase (Ki/Km 0.06). Inhibition of IMP dehydrogenase by EICAR 5'-monophosphate is competitive with respect to IMP. L1210 cells that were selected for resistance to the cytostatic action of EICAR proved to be adenosine kinase-deficient. Also, studies with other mutant L1210 and CEM cell lines revealed that adenosine kinase, as well as an alternative pathway, may be responsible for the conversion of EICAR to its 5'-monophosphate. Purified 2'-deoxycytidine kinase, 2'-deoxyguanosine kinase, cytosolic 5'-nucleotidase, and nicotinamide dinucleotide (NAD) pyrophosphorylase do not seem to be markedly involved in the metabolism of EICAR.
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PMID:Eicar (5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide). A novel potent inhibitor of inosinate dehydrogenase activity and guanylate biosynthesis. 790 Dec 17

This study was conducted to elucidate the role of S-adenosyl-L-homocysteine (SAH) hydrolase, 5'-nucleotidase and adenosine kinase in the production and removal of adenosine in the isolated guinea pig heart during normoxic (95% O2) and hypoxic (30% O2) perfusion. Using an adenosine kinase inhibitor (5'-amino-5'-deoxy-adenosine; 50 microM) and an adenosine deaminase inhibitor (EHNA; 5 microM) the total steady-state production rate of adenosine in the heart was estimated to be greater than 1.2 nmol.min-1 per g wet wt., during normoxia. Most (95%) of the SAH-derived adenosine is salvaged by adenosine kinase action. The rate of adenosine phosphorylation increased 3-fold when isolated hearts were perfused with hypoxic medium, suggesting that adenosine kinase is not substrate-saturated under normoxic conditions. The steady-state production of adenosine was also estimated during hypoxia (5.9 nmol-min-1 per g wet wt.) and compared with previously determined transmethylation rate during hypoxia (1.12 nmol.min-1 x g wet wt.). In an attempt to assess the in-vivo activity of cytosolic 5'-nucleotidase, the 5'-AMP pool was labelled by perfusing the isolated hearts with tricyclic nucleoside (TCN) which became phosphorylated (TCN-P). The release rate of both adenosine and TCN in the post-labelling phase was increased by hypoxic perfusion, suggesting that the increased rate of 5'-AMP hydrolysis may be due to increased availability of substrate, as well as activation of 5'-nucleotidase. Our findings suggest that during normoxic perfusion a significant amount of adenosine is derived from an apparently oxygen-independent mechanism (cellular transmethylation) whereas during hypoxic perfusion hydrolysis of adenine nucleotides to adenosine prevails.
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PMID:Adenosine metabolism in the guinea pig heart: the role of cytosolic S-adenosyl-L-homocysteine hydrolase, 5'-nucleotidase and adenosine kinase. 829 79

The role of adenosine as a metabolic regulator of physiological processes in the brain was studied by measuring its concentrations and the activity of adenosine-metabolizing enzymes: 5'-nucleotidase, S-adenosylhomocysteine hydrolase, adenosine deaminase and adenosine kinase in the cerebral cortex of the rat. Other purine compounds, such as, inosine, hypoxanthine and adenine nucleotides were also studied. The purines' pattern was bimodal with high levels of adenosine, inosine and hypoxanthine during the light period reaching their peak at 12.00 h, 08.00 h and 16.00 h, respectively, and small increments during the night between 02.00 h and 04.00 h. The enzymatic activities showed, in general, an unimodal profile with low activity during the day and high activities at night. The adenine nucleotide profile showed a significant diminution between 12.00 h and 24.00 h. The high adenosine level during the day might be due to a diminution of adenine nucleotide and to the low activity of adenosine-metabolizing enzymes, suggesting an accumulation of the nucleoside. The night increase, although of less magnitude, is simultaneous to high activity of adenosine-metabolizing enzymes and could be due to an increased formation of the nucleoside. The present data and the findings from other authors strongly suggest that adenosine in the brain cortex of the rat can participate at least in two physiological processes: regulation of the sleep-wake cycle and replenishment of the adenine nucleotide pool.
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PMID:Day-night variations of adenosine and its metabolizing enzymes in the brain cortex of the rat--possible physiological significance for the energetic homeostasis and the sleep-wake cycle. 833 Jan 91


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