Polyamine biosynthesis in rat prostate. Substrate and inhibitor properties of 7-deaza analogs of decarboxylated S-adenosylmethionine and 5'-methylthioadenosine

Abstract
The 7-deaza analogue of 5''-methylthioadenosine, a nucleoside end product in polyamine biosynthesis, was synthesized. This analogue competitively inhibits the hydrolytic cleavage of the purine-ribose bond in methylthioadenosine with Ki .simeq. Km. The 7-deaza analogue of decarboxylated S-adenosylmethionine, a cofactor in the biosynthesis of both spermidine and spermine, was synthesized. This analogue acts as a substrate in the reaction catalyzed by spermidine synthease, in which severe substrate inhibition by both the normal nucleoside substrate and the 7-deaza analogue is observed. These results are discussed in terms of possible end product regulation of polyamine biosynthesis and the possible substitution of the nucleoside antibiotic, tubercidin, for adenosine in reactions involving S-adenosylmethionine and its metabolites.

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