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 toxicology and pharmacology of formycin both as a single agent and combined with the adenosine deaminase inhibitor 2'-deoxycoformycin (dCF) were examined in outbred Swiss mice heterozygous for the nude gene (nu/+). The LD10 for formycin alone given on a daily x 5 schedule was 21 mg/kg. When the animals were pretreated with 1 mg/kg of dCF 1 hour prior to each dose of formycin, toxicity was approximately doubled, ie, LD10 was reduced to 10 mg/kg. Death was associated with hepatic toxicity in both treatment regimens; suppression of leukocyte counts was mild except at doses greater than the LD10. Formycin nucleotides were detected by high-performance liquid chromatography in the livers of mice treated with formycin either alone or combined with dCF. When isolated rat hepatocytes were incubated for 2 hours with either formycin or dCF plus formycin, analog nucleotides accumulated in the cells. Cellular ATP decreased to below the limits of detection, whereas a large peak corresponding to formycin-5'-triphosphate was present. This replacement of cellular ATP by formycin-5'-triphosphate may help explain the hepatic toxicity observed.
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PMID:Biochemical pharmacology and toxicology of formycin alone and in combination with 2'-deoxycoformycin (pentostatin). 660 Sep 68

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.
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PMID:Adenylate degradation in Escherichia coli. The role of AMP nucleosidase and properties of the purified enzyme. 700 Jul 83