Effect of analogues of 5′-methylthioadenosine on cellular metabolism. Inactivation of S-adenosylhomocysteine hydrolase by 5′-isobutylthioadenosine

Publisher Website
Google Scholar
Abstract
The effects of a number of nucleosides related to 5′-methylthioadenosine on the activities of S-adenosylhomocysteine hydrolase, 5′-methylthioadenosine phosphorylase, spermidine synthase and spermine synthase were investigated. Both 5′-methylthioadenosine and 5′-isobutylthioadenosine gave rise to an enzyme-activated irreversible inhibition of S-adenosylhomocysteine hydrolase, but 5′-methylthiotubercidin (5′-methylthio-7-deaza-adenosine), 5′-deoxy-5′-chloroformycin, 5′-ethylthio-2-fluoro-adenosine and 1,N6-etheno-5′-methylthioadenosine were totally ineffective in producing this inactivation. Of the nucleosides tested, only 5′-methylthioadenosine, 5′-methylthiotubercidin and 5′-isobutylthioadenosine were inhibitory towards the aminopropyltransferases responsible for the synthesis of spermine and spermidine. 5′-Methylthiotubercidin, 5′-deoxy-5′-chloroformycin and 5′-isobutylthioadenosine were inhibitors of the degradation of 5′-methylthioadenosine by 5′-methylthioadenosine phosphorylase, but only 5′-isobutylthioadenosine was also a substrate for this enzyme. These results suggest that the effects of 5′-isobutylthioadenosine of the cell may result from the combination of inhibitory actions on polyamine synthesis, 5′-methylthioadenosine degradation and S-adenosylhomocysteine degradation. The resulting increased concentrations of S-adenosylhomocysteine could bring about inhibition of methyltransferase reactions. A new convenient method for the assay of S-adenosylhomocysteine hydrolase in the direction of synthesis is described.

This publication has 34 references indexed in Scilit: