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)

1. The metabolic control of adenosine concentration in the rat liver through the 24-hr cycle is related to the activity of adenosine-metabolizing enzymes [5'-nucleotidase (5'N), adenosine deaminase (A.D.), adenosine kinase (A.K.) and S-adenosylhomocysteine hydrolase (SAH-H)]. 2. Two peaks of adenosine were observed, one at 12:00 hr caused by high activity of 5'N and SAH-H, and the other at 02:00 hr, caused by a decrease in purine catabolism and purine utilization, low activity of SAH-H and de novo purine formation. 3. The similarity of the adenosine and S-adenosylmethionine (SAM) profiles through the 24-hr cycle suggests a role of adenosine in transmethylation reactions, because, during the night (02:00 hr), the metabolic conditions favor the formation and accumulation of S-adenosylhomocysteine (SAH), with consequent inhibition of transmethylation reactions. 4. In the 24-hr variation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE), the lowest ratio of PC/PE was observed at 24:00-02:00 hr when SAH concentration is high, whereas the highest PC/PE ratio occurs at the same time as one of the SAM/SAH ratio maxima.
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PMID:Twenty-four-hour changes of S-adenosylmethionine, S-adenosylhomocysteine adenosine and their metabolizing enzymes in rat liver; possible physiological significance in phospholipid methylation. 176 Nov 53

Adenosine derivatives are frequently used in chemotherapy because of their potent antitumor, antiviral and antiparasitic activity. We investigated the metabolism of some adenosine analogues in adenosine deaminase inhibited normal and adenine phosphoribosyltransferase (APRT) deficient human erythrocytes. The ATP and GTP concentrations and the formation of unusual nucleotides were measured. Some of the analogues studied (tubercidin, 9 beta-D-arabinofuranosyladenine, 2'-deoxyadenosine, 2-chloroadenosine, neplanocin A) were phosphorylated to the corresponding nucleoside triphosphates and this process was abolished by iodotubercidin--an adenosine kinase inhibitor. With the exception of 2'-deoxyadenosine, nucleotide analogue formation was accompanied by ATP depletion. ATP decrease was not observed after adenosine kinase inhibition and ATP concentration even increased in the presence of 2'-deoxyadenosine, neplanocin A and 5'-iodo-5'-deoxyadenosine. However, the latter increment was not observed in APRT deficient erythrocytes. Bredinin, S-adenosylhomocysteine, deoxycoformycin and adenosine dialdehyde did not form nucleotide derivatives or exert any effects on ATP concentration. It is concluded that adenosine analogues can either enter the nucleotide pool via phosphorylation mechanisms, or may be converted to ATP by the pathways involving the intermediate formation of adenine.
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PMID:Effects of adenosine analogues on ATP concentrations in human erythrocytes. Further evidence for a route independent of adenosine kinase. 193 Mar 1

The stereoenantimers D-[3H]adenosine and L-[3H]adenosine were used to study adenosine accumulation in rat cerebral cortical synaptoneurosomes. L-Adenosine very weakly inhibited rat brain adenosine deaminase (ADA) activity with a Ki value of 385 microM. It did not inhibit rat brain adenosine kinase (AK) activity, nor was it utilized as a substrate for either ADA or AK. The rate constants (fmol/mg of protein/s) for L-[3H]adenosine accumulation measured in assays where transport was stopped either with inhibitor-stop centrifugation or with rapid filtration methods were 82 +/- 14 and 75 +/- 10, respectively. Using the filtration method, the rates of L-[3H]adenosine accumulation were not significantly different from the value of 105 +/- 15 fmol/mg of protein/s measured for D-[3H]adenosine transport. Unlabeled D-adenosine and nitrobenzylthiolnosine, both at a concentration of 100 microM, reduced the levels and rates of L-[3H]adenosine accumulation by greater than 44%. These findings suggest that L-adenosine, a metabolically stable enantiomeric analog, and the naturally occurring D-adenosine are both taken up by rat brain synaptoneurosomes by similar processes, and as such L-adenosine may represent an important new probe with which adenosine uptake may be studied.
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PMID:L-[3H]adenosine, a new metabolically stable enantiomeric probe for adenosine transport systems in rat brain synaptoneurosomes. 198 56

The hypothesis that adenosine metabolizing enzymes may have a key role in the transport of adenosine is discussed. The enhancement of adenosine transport by inhibitors of adenosine deaminase (the enzyme which deaminates adenosine to inosine) and the ecto-localization of adenosine deaminase suggest a contribution of the enzyme in taking up nucleosides. Two possible mechanisms are suggested: 1) transport and deamination of adenosine as a coupled process, or 2) uptake of inosine after cleavage of adenosine by ecto-adenosine deaminase. In both cases, the so-called adenosine deaminase binding protein which is a membrane protein could be the real nucleoside transporter. This behaviour of adenosine deaminase as an ectoenzyme anchored to a membrane protein remembers the behaviour of periplasmic binding proteins of bacteria. Thus, adenosine deaminase as well as, for instance, adenosine kinase would be a kind of 'periplasmic proteins' of eukaryotic cells. The function of adenosine deaminase and adenosine kinase would then be to take adenosine and give it to the true transporters.
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PMID:Is adenosine deaminase involved in adenosine transport? 209 Sep 26

Our earlier work on reperfusion showed that adult rat hearts released almost twice as much purine nucleosides and oxypurines as newborn hearts did [Am J Physiol 254 (1988) H1091]. A change in the ratio anabolism/catabolism of adenosine could be responsible for this effect. We therefore measured the activity of adenosine kinase, adenosine deaminase, nucleoside phosphorylase and xanthine oxidoreductase in homogenates of hearts and myocytes from neonatal and adult rats. In hearts the activity of adenosine deaminase and nucleoside phosphorylase (10-20 U/g protein) changed relatively little. However, adenosine kinase activity decreased from 1.3 to 0.6 U/g (P less than 0.025), and xanthine oxidoreductase activity increased from 0.02 to 0.85 U/g (P less than 0.005). Thus the ratio in activity of these rate-limiting enzymes for anabolism and catabolism dropped from 68 to 0.68 during cardiac development. In contrast, the ratio in myocytes remained unchanged (about 23). The large difference in adenosine anabolism/catabolism ratio, observed in heart homogenates, could explain why ATP breakdown due to hypoxia is lower in neonatal than in adult heart. Because this change is absent in myocytes, we speculate that mainly endothelial activities of adenosine kinase and xanthine oxidoreductase are responsible for this shift in purine metabolism during development.
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PMID:Ischemic nucleotide breakdown increases during cardiac development due to drop in adenosine anabolism/catabolism ratio. 209 32

In isolated hepatocytes from fasted rats, 0.5 mM adenosine inhibited gluconeogenesis from glutamine, lactate and pyruvate. This inhibition was due to adenosine conversion through adenosine kinase. An increase in ketone body release was only observed in the presence of lactate or pyruvate, and the two phenomena (i.e. inhibition of gluconeogenesis and increased ketone-body release) were linked. With alanine, dihydroxyacetone or serine as substrates, adenosine did not change gluconeogenesis; however, its conversion through adenosine kinase also inhibited gluconeogenesis. With asparagine as substrate, 0.5 mM adenosine increased gluconeogenesis; this increase was due to adenosine conversion through adenosine deaminase. However, adenosine conversion through adenosine kinase inhibited gluconeogenesis from asparagine. Thus, whatever the substrate used, adenosine conversion through adenosine kinase inhibited gluconeogenesis. The inhibitory effect of adenosine on gluconeogenesis cannot be related to the decrease in Pi concentration and to the increase in ATP pool. Beside its effect on gluconeogenesis, adenosine inhibited ketogenesis measured without added substrate; adenosine conversion through adenosine kinase was also involved in the inhibition of ketogenesis.
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PMID:Metabolism of adenosine through adenosine kinase inhibits gluconeogenesis in isolated rat hepatocytes. 215 47

The mechanism by which S-adenosylmethionine (SAM) and adenosine (Ado) increase ATP levels in intact human erythrocytes in vitro has been compared. The use of erythrocytes from healthy controls and from subjects totally deficient in adenine phosphoribosyltransferase (APRT), plus inhibitors of adenosine kinase (AK) and adenosine deaminase (ADA) separately and together, has enabled us to demonstrate that this increment in ATP levels occurred via totally different metabolic routes. The results show that: (i) whilst the Ado-induced increment in ATP was AK dependent, that produced by SAM was independent of AK: and (ii) the SAM-induced increment in ATP was totally dependent on APRT and that some of the increment produced by Ado might also be APRT dependent. The above data are consistent with the metabolism of SAM to ATP by a route recently identified by us whereby ATP is formed from deoxyadenosine: namely binding to the enzyme S-adenosylhomocysteine hydrolase with subsequent release of adenine and further conversion to ATP via APRT.
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PMID:S-adenosylmethionine increases erythrocyte ATP in vitro by a route independent of adenosine kinase. 226 Sep 86

Previous results demonstrated that the adenosine that accumulates in human fat cell suspensions is derived from extracellular sources (Kather, H. (1988) J. Biol. Chem. 263, 8803-8809). To get insight into the mechanisms responsible for the lack of adenosine release, extracellular adenine nucleotide catabolism was minimized by 10 mmol/liter beta-glycerophosphate and 10 mumol/liter alpha,beta-methyleneadenosine 5'-diphosphate. Intracellular adenine nucleotide catabolism resulted in a release of inosine and hypoxanthine under these conditions that was increased markedly by isoproterenol. Experiments with inhibitors of adenosine deaminase and adenosine kinase indicated that the production of inosine and hypoxanthine proceeded via AMP deamination. Consistently, IMP levels were increased transiently in the presence of isoproterenol. In addition, the cells possessed a nucleotide phosphomonoesterase that was resistant to the inhibitory actions of ATP and alpha,beta-methyleneadenosine 5'-diphosphate and showed preference for IMP over AMP. Adenosine (approximately 1 nmol/10(6) cells/h) was also produced inside the cells. However, adenosine production was unrelated to ATP turnover via adenylate cyclase, and any adenosine formed was immediately reconverted to adenine nucleotides in the absence and presence of isoproterenol. It was concluded that adenosine is not released by intact human adipocytes, because the alternative routes of intracellular AMP catabolism are compartmentalized (at least in functional terms), and adenosine kinase is not saturated with substrate in the absence and presence of isoproterenol.
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PMID:Pathways of purine metabolism in human adipocytes. Further evidence against a role of adenosine as an endogenous regulator of human fat cell function. 229 25

The activities (Vmax) of several enzymes of purine nucleotide metabolism were assayed in premature and mature primary rat neuronal cultures and in whole rat brains. In the neuronal cultures, representing 90% pure neurons, maturation (up to 14 days in culture) resulted in an increase in the activities of guanine deaminase (guanase), purine-nucleoside phosphorylase (PNP), IMP 5'-nucleotidase, adenine phosphoribosyltransferase (APRT), and AMP deaminase, but in no change in the activities of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenosine deaminase, adenosine kinase, and AMP 5'-nucleotidase. In whole brains in vivo, maturation (from 18 days of gestation to 14 days post partum) was associated with an increase in the activities of guanase, PNP, IMP 5'-nucleotidase, AMP deaminase, and HGPRT, a decrease in the activities of adenosine deaminase and IMP dehydrogenase, and no change in the activities of APRT, AMP 5'-nucleotidase, and adenosine kinase. The profound changes in purine metabolism, which occur with maturation of the neuronal cells in primary cultures in vitro and in whole brains in vivo, create an advantage for AMP degradation by deamination, rather than by dephosphorylation, and for guanine degradation to xanthine over its reutilization for synthesis of GMP. The physiological meaning of the maturational increase in these two ammonia-producing enzymes in the brain is not yet clear. The striking similarity in the alterations of enzyme activities in the two systems indicates that the primary culture system may serve as an appropriate model for the study of purine metabolism in brain.
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PMID:Developmental changes in the activity of enzymes of purine metabolism in rat neuronal cells in culture and in whole brain. 232 47

The present study describes the effects of the inhibition of adenosine deaminase and of adenosine kinase on reticulocytes and erythrocytes of rabbits. Both in erythrocytes and in reticulocytes the degradation of adenine nucleotides proceeds via AMP----IMP----inosine----hypoxanthine. Under approximately physiological conditions the rate of degradation amounts in erythrocytes to 23 mumoles/l cells.h and in reticulocytes to 331 mumoles/l cells.h, respectively. In erythrocytes the formation of hypoxanthine corresponds closely to the degradation of adenine nucleotides in reticulocytes; the formation of hypoxanthine seems to exceed the degradation presumably mainly due to RNA degradation. Parallel to the primary deamination of AMP there is a primary dephosphorylation to adenosine of about 60 mumoles/l cells.h in erythrocytes and about 300 mumoles/l cells.h in reticulocytes. This pathway does not provide, however, any measurable contribution to the formation of hypoxanthine, because the adenosine formed is rephosphorylated via adenosine kinase almost completely.
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PMID:Catabolism of adenine nucleotides in rabbit blood cells. 236 Sep


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