Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

Because micromolar concentrations of adenosine (Ado) have been documented recently in the interstitial fluid of carcinomas growing in animals, we examined the effects of low concentrations of Ado on the growth of cultured human carcinoma cells. Ado alone had little effect upon cell growth. In the presence of one of a number of Ado deaminase (ADA) inhibitors, Ado led to significant growth inhibition of all cell lines tested. Similar effects were found when ATP, ADP, or AMP was substituted for Ado. Surprisingly, the ADA inhibitor coformycin (CF) had a much greater potentiating effect than did 2'-deoxycoformycin (DCF), although DCF is a more potent ADA inhibitor. The growth inhibition of the Ado/CF combination was not abrogated by pyrimidines or caffeine, a nonspecific Ado receptor blocker. Toxicity was prevented by the addition of the Ado transport inhibitor dipyridamole or the Ado kinase inhibitor 5'-amino 5'-deoxyadenosine. S-Adenosylhomocysteine hydrolase is not involved because neither homocysteine thiolactone nor an S-adenosylhomocysteine hydrolase inhibitor (adenosine dialdehyde) potentiated toxicity of the Ado/CF combination. Unexpectedly, substitution of 2'-deoxyadenosine (the toxic moiety in congenital ADA deficiency) for Ado, did not lead to equivalent toxicity. The Ado/CF combination inhibited DNA synthesis and brought about morphological changes consistent with apoptosis. Together, these findings indicate that the Ado-mediated killing proceeds via an intracellular route that requires the action of Ado kinase. The enhanced cofactor activity of CF may be attributable to its being a more potent inhibitor of AMP deaminase than is DCF.
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PMID:Adenosine-mediated killing of cultured epithelial cancer cells. 1076 76