Inactivation and Reactivation of Intracellular S-Adenosyihomocysteinase in the Presence of Nucleoside Analogues in Rat Hepatocytes1
نویسندگان
چکیده
Several nucleoside analogues, some of which are potent inactivators of isolated S-adenosylhomocysteinase (AdoHcyase), were tested with respect to their effect on intracellular Ado Hcyase and S-adenosylhomocysteine (AdoHcy) catabolism in intact rat hepatocytes. Among the analogues tested, 9-/3-Darabinofuranosyladenine and 9-/3-o-arabinofuranosyl-3-deazaadenine were the most potent inactivators of intracellular Ado Hcyase. Compounds like 2-chloroadenosine and carbocyclic adenosine are extremely efficient inactivators of the isolated enzyme, but these nucleosides exerted only a limited effect on the enzyme in intact hepatocytes. Only a moderate effect was observed with 2-chloro-3-deazaadenosine and 2'-deoxyadenosine, and a high concentration of 5'-deoxy-5'-methylthioadenosine was required to inactivate the enzyme. There was a corre lation between inactivation and accumulation of AdoHcy. Carbocyclic-3-deazaadenosine caused no inactivation of AdoHcyase in liver cells but caused a massive accumulation of AdoHcy, suggesting that this analogue functions as a reversible inhibitor of the enzyme. Residual enzyme activity was observed with all the nucleoside analogues tested. The intracellular enzyme inac tivated in the presence of 2'-deoxyadenosine and 9-0-D-arabinofuranosyladenine was readily recovered when the cells were transferred to fresh medium containing adenosine deaminase, but reactivation of the enzyme activity after treatment of the cells with 2-chloroadenosine and 5'-deoxy-5'-methylthioadenosine was also observed. The inactivation of intracellular enzyme in duced by 2-chloro-3-deazaadenosine, 9-/3-o-arabinofuranosyl-3deazaadenine, and carbocyclic adenosine was essentially irre versible under the conditions of the experiments. Factors deter mining the effect of nucleoside analogues on intracellular Ado Hcyase are discussed.
منابع مشابه
Inactivation and reactivation of intracellular S-adenosylhomocysteinase in the presence of nucleoside analogues in rat hepatocytes.
Several nucleoside analogues, some of which are potent inactivators of isolated S-adenosylhomocysteinase (AdoHcyase), were tested with respect to their effect on intracellular AdoHcyase and S-adenosylhomocysteine (AdoHcy) catabolism in intact rat hepatocytes. Among the analogues tested, 9-beta-D-arabinofuranosyladenine and 9-beta-D-arabinofuranosyl-3-deazaadenine were the most potent inactivato...
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تاریخ انتشار 2006