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

---

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

The kinetic parameters (Km and Vmax) of sugar-modified analogues of inosine and guanosine have been determined with human erythrocytic purine nucleoside phosphorylase (PNP). Steric alterations at the 2' and 3' positions greatly lessened or abolished substrate activity. However, the 5'-deoxy- and 2',5'-dideoxy-beta-D-ribofuranosyl and the alpha-L-lyxosyl analogues were good substrates, indicating that the 5'-hydroxyl and the orientation of the 5'-hydroxy-methyl group are not important for binding. The sugar phosphate analogue, 5-deoxyribose 1-phosphate, was synthesized from 5'-deoxyinosine with immobilized PNP, and its presence was verified by using it in the enzymic synthesis of 5'-deoxyguanosine. The adenosine versions of the 5'-modified analogues were also found to react with adenosine deaminase, albeit at less than 1% of Vmax.
...
PMID:Human erythrocytic purine nucleoside phosphorylase: reaction with sugar-modified nucleoside substrates. 676 10

Restoration of coronary flow after hyperkalemic cardioplegic arrest (HCA) is associated with a unique metabolic reperfusion injury (RI) manifested by declining nucleotide stores despite their end-ischemic preservation. Prevention of this RI by exogenous provision of adenosine with or without inhibition of adenosine's major catabolic enzyme was assessed in 27 dogs subjected to 60 minutes of HCA. The effect of aortic root infusion of 40 mg/kg of adenosine in addition to adenosine deaminase inhibition by 10 mg/kg of EHNA (group 2) initiated during 60 minutes of reperfusion on myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores and coronary blood flow (CBF) were compared to animals having adenosine infusion alone (group 3) or controls (group 1). Although ATP levels were preserved at the end of HCA in all groups, adenosine infusion with or without EHNA prevented the significant 23 percent decline in ATP stores incurred during unmodified reperfusion (p less than 0.01, group 1). The CP stores decreased (p less than 0.05, all groups) during arrest, but were restored to preischemic levels during reperfusion. When measured 60 minutes after aortic unclamping, CBF was 312 percent of preischemic flow in group 3 (p less than 0.01), only 170 percent in group 2 (p less than 0.05), and unchanged in controls (group 1). The data indicate that provision of adenosine as a nucleotide precursor prevents the metabolic RI following HCA. In addition, inhibition of adenosine catabolism is not necessary for this salutary effect, nor is adenosine's efficacy solely mediated by augmentation of CBF.
...
PMID:Beneficial metabolic effect of nucleoside augmentation on reperfusion injury following cardioplegic arrest. 683 23

Alteration of membrane fluidity during enzymatic methylation of membrane phosphatidyl-ethanolamine (PE) and neutralization of negative charges of membrane proteins due to methylation of carboxyl groups may contribute to sperm motility. Therefore, enzymatic phospholipid methylation and carboxymethylation, and the consequences of their inhibition on motility, were studied using human sperm. These studies gave the following results. Human sperm homoganates contained two phospholipid N-methyltransferases (PMT) which converted PE to phosphatidylcholine (PC) in the presence of S-adenosylmethionine (SAM). The first PMT converted PE to phosphatidyl-N-methylethanolamine (PME). In had a Km of 4.0 microM and a pH optimum of 8.0. The second PMT converted PME to phosphatidyl-N,N-dimethylethanolamine and PC. It had a Km of 71 microM and a pH optimum of 10.0. Spermatozoa also contained protein carboxymethylase (PCM) and methyl aceptor protein (MAP). The intracellular levels of S-adenosylhomocysteine (SAH), an inhibitor of SAM-mediated methylations, were increased by adding adenosine (100 microM), L-homocysteine thiolactone (L-HCT, 10 microM), and erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA, 10 microM), an inhibitor of adenosine deaminase, to human sperm ejaculates that had been diluted with sodium phosphate buffer at pH 7.4 and 25 degrees. The motility index of each sperm suspension was determined every hour for 4 hr. In the presence of the mixture of adenosine, L-HCT and EHNA, the motility index was depressed by 57%. Under similar conditions, phospholipid methylation was depressed by 48%. Similar experiments were also conducted in the presence of 3-deazaadenosine (Deaza, 80 microM), a selective inhibitor of SAH hydrolase. In the presence of adenosine and L-HCT, Deaza depressed the motility index by 60% and phospholipid methylation by 86%. The potencies of SAH in the inhibition of phospholipid methylation and protein carboxymethylation in sperm homogenates had the following order: PMT I greater than PCM greater than PMT II. These observations indicate that the PMT system and/or the PCM-MAP system play a significant role in the regulation of human sperm motility.
...
PMID:Depression of human sperm motility by inhibition of enzymatic methylation. 686 Mar 62

Extracts of Escherichia coli K12 degrade AMP to hypoxanthine, adenine, adenosine, and inosine. Degradation experiments with mutants which lack purine nucleoside phosphorylase or both purine nucleoside phosphorylase and adenosine deaminase demonstrate that hypoxanthine formation is dependent on purine nucleoside phosphorylase. These findings are consistent with an absence of adenine deaminase activity in E. coli. Adenine is formed from AMP in extracts of the E. coli mutants as well as the wild type cells. This activity is due to AMP nucleosidase. Purified, homogeneous AMP nucleosidase gives a subunit Mr = 52,000 on denaturing gel electrophoresis and an oligomer molecular weight of approximately 280,000 by comparative gel filtration. Kinetic studies with this enzyme give cooperative initial rate curves with AMP as substrate, with MgATP2- as an activator, and with Pi as an inhibitor. Phosphate inhibition is competitive with McATP2- (Ki = 0.2 mM) and reverses the activation by MgATP2-. In the absence of MgATP2-, the apparent S0.5 for AMP is 15 mM and decreases to 90 microM at saturating MgATP2-. The maximum rate of AMP hydrolysis is not affected by MgATP2-. Kinetics of MgATP2- activation give a constant for half-maximum activation varying from 120 microM in the presence of low AMP to approximately 2 microM when AMP is present at near saturation. Formycin 5'-PO4 is a powerful competitive inhibitor with respect to AMP, giving a Kis of 72 nM and a Km/Kis ratio of 1,200. Adenylate degradation experiments indicate that AMP nucleosidase is the major enzyme of AMP catabolism in E. coli. The kinetic properties of the purified enzyme indicate that regulation occurs by the intracellular MgATP2- /Pi ratio and the concentration of AMP.
...
PMID:Adenylate degradation in Escherichia coli. The role of AMP nucleosidase and properties of the purified enzyme. 700 Jul 83

Strains of Escherichia coli K-12 containing both pnd1 mutation, rendering bacteria capable to catabolize purine nucleosides without participation of purine nucleoside phosphorylase (pup gene), and mutations in several genes of purine metabolism or nucleosides catabolism have been constructed. The introduction of the deletion mutation in adenosine deaminase gene (add) into the pup pnd genome does not affect the ability of mutants to utilize adenosine and deoxyadenosine as the sole carbon and energy sources. Mutations affecting purine phosphoribosyltransferases (hpt and gpt) block the ability of pup pnd mutants to utilize hypoxanthine, guanine and their deoxyribonucleosides and also xanthine and xanthosine as the only purine source. A mutation in deoxyribomutase (drm) disturbs the ability of pnd mutants to use all purine ribo- and deoxy-ribonucleosides as carbon and energy sources, whereas a mutation in deoxyriboaldolase (dra) only disturbs utilization of deoxyribonucleosides. These data seem to indicate that the activity promoted by pnd mutations catalyzes the cell reaction of irreversible phosphorolytic cleavage of the N-glycoside bond of the purine nucleosides molecules: purine nucleoside + phosphate leads to purine + pentose-1-phosphate. It is suggested that pnd mutations affect the structural gene of some phosphorolytic enzyme and modify its substrate specificity. Evidence is presented that the structural gene of a new nucleoside phosphorylase is not sensitive to catabolite repression.
...
PMID:[Phenotypic manifestation of the pnd mutation, which promotes purine nucleoside cleavage by Escherichia coli K-12 cells, in the genome of strains defective in the metabolism of nucleic acid precursors]. 701 63

Adrenaline and adenosine deaminase decreased the rate of phosphate uptake in isolated rat adipocytes. This effect was inhibited by N6(phenylisopropyl)adenosine. The rate of uptake was decreased by one third if the rats were given triiodothyronine prior to killing. In fat cells from hypothyroid rats, phosphate uptake was not sensitive to adrenaline. Sensitivity was restored by exogenous adenosine deaminase.
...
PMID:Regulation of phosphate uptake in rat adipocytes by adenosine, catecholamines and thyroid hormones. 723 35

1. The liberation of ammonia from adenosine 5'-phosphate (AMP) and adenosine and the release of inorganic phosphate from AMP were investigated in homogenates of bovine and human parotid glands. 2. Adenosine phosphate deaminase (AMP deaminase) was purified from bovine and human parotid glands. The enzyme preparations obtained were free from adenosine deaminase and 5'-nucleotidase activities. 3. AMP incubated with human parotid gland homogenate produced inosine 5'-phosphate, adenosine, inosine and ammonia. The amount of ammonia accumulating in the incubation mixture was equal to the sum of inosine 5'-phosphate plus inosine. 4. These results demonstrate the presence in human parotid of AMP deaminase and adenosine deaminase.
...
PMID:Deamination of adenosine 5'-phosphate and adenosine as a possible source of ammonia in human and bovine parotid glands. 724 42

A new spectrophotometric method for the determination of adenosine deaminase is described. Adenosine is deaminated to inosine, the latter is cleaved by an inosine-guanosine specific nucleoside phosphorylase to hypoxanthine and ribose-1-phosphate. Hypoxanthine can be oxidized further to uric acid by xanthine oxidase or to allantoin by xanthine oxidase and uricase. The hydrogen peroxide formed in these reactions is reduced by catalase to water. In the presence of high concentrations of ethanol, equivalent amounts of acetaldehyde are produced. The acetaldehyde is oxidized NAD(P) dependent and the production rate of NAD(P)H is recorded at 334 nm. The new method is suitable for the detection of adenosine deaminase in whole blood, lymphocytes, sera and tissues.
...
PMID:A new spectrophotometric assay for enzymes of purine metabolism. IV. Determination of adenosine deaminase. 736 76

Relative to lymphoid cells and normal fibroblasts, mouse melanoma cells (B16) were moderately sensitive to adenosine, with 80% growth inhibition being observed at 50 micro M adenosine instead of at 5 micro M as was reported with lymphoid cells or 400 micro M as was reported for normal fibroblasts. These differences were not due to adenosine deaminase because lymphoid cells had two to four times more of this activity than did melanoma cells or normal fibroblasts. In melanoma cells, complete adenosine-induced growth inhibition was a gradual process which was observed only after one to two population doublings; after 4 days of treatment, complete recovery was gradual requiring 48 hr. N6,O2-Dibutyryladenosine-cyclic-3':5' phosphate and polyadenylic acid were ineffective as growth inhibitors, whereas guanosine exhibited potent growth-inhibiting properties. Homocysteine thiolactone enhanced the cytotoxicity of adenosine but not guanosine; adenosine relieved the cytotoxicity of guanosine. These observations indicated that the two purine nucleosides were exerting their growth-inhibiting effects by different mechanisms. Uridine did not relieve adenosine-induced cytostasis, but at 50 micro M adenosine enhanced the incorporation of [3H]uridine into RNA. This suggested that the uridine phosphate pools were depleted at low adenosine concentrations and that exogenous adenosine influences the availability of pyrimidines.
...
PMID:Characterization of adenosine-induced cytostasis in melanoma cells. 738 82

The effects of 2-chloro-2'-deoxyadenosine (2CdA) on the activity of enzymes important for the metabolism of deoxyadenosine were studied in lysates prepared from human primary central nervous system (CNS) lymphomas and normal human lymphocytes. Strong inhibition (approximately 100%) of the phosphorylation of deoxyadenosine to its deoxynucleotide phosphate derivatives was produced in both systems in the presence of 2CdA, which was phosphorylated concomitantly to 2-chloro-2'-deoxyAMP. Interestingly, 2CdA was also found to be an inhibitor of the deamination of both deoxyadenosine (over 50%) and AMP (70%). These findings add to our understanding of the mechanisms of toxicity of this drug, especially considering that 2CdA is resistant to deamination by adenosine deaminase. These results challenge the existing theories of 2CdA toxicity, which have been limited to the formation of phosphate derivatives of 2CdA. The present in vitro studies have demonstrated that 2CdA also inhibits both phosphorylation and deamination of deoxyadenosine (dAdo), suggesting that its mechanism of toxicity includes a block in dAdo metabolic pathways. This has important implications for the perturbation of cell methylation, a functionality associated with, for example, apoptosis.
...
PMID:The influence of 2-chloro-2'-deoxyadenosine on metabolism of deoxyadenosine in human primary CNS lymphoma. 750 87


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---