Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

9-beta-D-Arabinofuranosyladenine (ara-A) inactivates isolated S-adenosyl-L-homocysteine (AdoHcy) hydrolase (EC 3.3.1.1) as well as AdoHcy hydrolase in intact cells. Whereas the inactivation in cell-free systems is an irreversible process, the AdoHcy hydrolase activity in rat hepatocytes exposed to ara-A gradually recovered upon prolonged incubation of the cells in a medium devoid of ara-A. This process, tentatively termed reactivation of the enzyme, was nearly totally dependent on a high level of adenosine deaminase in the extracellular medium, which induced a decrease in intracellular content of adenosine as well as ara-A. Reactivation of intracellular enzyme was inhibited by adenosine deaminase inhibitors [2'-deoxycoformycin and erythro-9-(2-hydroxy-3-nonyl)adenine] and the synthetic substrate for AdoHcy hydrolase, 3-deazaadenosine. An inhibitor of protein synthesis (cycloheximide) was without effect. Homocysteine, which protected the intracellular AdoHcy hydrolase against inactivation by ara-A, induced no reactivation of the enzyme. The half-life of the intracellular ara-A-AdoHcy hydrolase complex was about 90 min and was not affected by adenosine deaminase, 3-deazaadenosine, or homocysteine added to the cell suspension. However, the rate of elimination of the complex in the hepatocytes exceeded the rate of reactivation of AdoHcy hydrolase. Thus, the elimination process accounted for the reactivation, but not correlation between these two processes was observed. Reactivation of intracellular AdoHcy hydrolase caused a pronounced fall in cellular content of AdoHcy. The possibility that reduced cellular level of AdoHcy induced the reactivation of AdoHcy hydrolase seemed unlikely. This statement was based on the observation that reactivation was observed also under conditions of high concentrations of AdoHcy (obtained by the addition of homocysteine to the cell suspension). Reactivation of AdoHcy hydrolase with a concomitant decrease in cellular level of AdoHcy could also be demonstrated with mouse plasmacytoma (MPC-11) cells and mouse fibroblasts (L-929) exposed to ara-A, but the reactivation process was far less pronounced than with hepatocytes.
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PMID:Reactivation of S-adenosylhomocysteine hydrolase activity in cells exposed to 9-beta-D-arabinofuranosyladenine. 697 84

The inactivation of S-adenosylhomocysteine (AdoHcy) hydrolase (EC 3.3.1.1) in isolated rat hepatocytes by 9-beta-D-arabinofuranosyladenine (ara-A) was associated with tight binding of ara-A to the enzyme and showed an initial phase obeying first-order kinetics characterized by Ki (concentration of half-maximal rate of inactivation) of 12 microM for ara-A and a maximal rate of inactivation of 0.7 min-1. Two to 3% of the enzyme in rat hepatocytes was not available for inactivation. Similar results were obtained with some cultured cells, including mouse plasmacytoma cells (MPC-11), mouse fibroblasts (L-929), and human chronic myelogenic leukemia cells (K-562). In a cellular medium devoid of adenosine deaminase, inhibitors of this enzyme did not affect the inactivation process in rat hepatocytes and only slightly enhanced this process in the cultured cells (at low concentrations of ara-A). Inactivation of AdoHcy hydrolase in rat hepatocytes was associated with a massive build-up of AdoHcy (from 75 to 5200 pmol/10(6) cells after 3 hr of incubation) and a moderate increase in cellular S-adenosylmethionine. The accumulation of AdoHcy in the cultured cells exposed to ara-A was less pronounced and no increase in cellular S-adenosylmethionine was observed. There was a quantitatively important export of AdoHcy from the rat hepatocytes and the cultured cells into the extracellular medium, whereas no leakage of S-adenosylmethionine was detected. The inactivation of AdoHcy hydrolase by ara-A in rat hepatocytes was inhibited in the presence of adenosine or homocysteine in the cellular medium. This effect of homocysteine correlated with increased cellular level of AdoHcy induced by this agent but was also associated with reduction in cellular uptake of ara-A.
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PMID:Inactivation of S-adenosylhomocysteine hydrolase by 9-beta-D-arabinofuranosyladenine in intact cells. 705 72