Action of decarboxylated S-adenosylmethionine analogs in the spermidine-synthesizing system from rat prostate

Abstract

Synthetic decarboxylated S-adenosylmethionine and its nine analogs, as well as four putrescine analogs, were examined in a polyamine-synthesizing system based on rat prostate spermidine synthase. In addition to the natural substrate, decarboxylated S-adenosylmethionine, S-5′-deoxyadenosyl-(5′)-3-ethylthiopropylamine, S-5′-deoxyadenosyl-(5′)-3-propylthiopropylamine, and S-5′-deoxyadenosyl-(5′)-3-butylthiopropylamine were all found to work as the aminopropyl donor to putrescine. Experiments with other analogs of decarboxylated S-adenosylmethionine indicated that the enzyme will transfer only the aminopropyl group, not an aminoethyl or aminobutyl group. The mammalian spermidine synthase could use only one of the two diastereoisomers of decarboxylated S-adenosylmethionine as the aminopropyl donor. The synthase could use 1,4-diamino-2-butene in addition to putrescine as the acceptor of the aminopropyl group from decarboxylated S-adenosylmethionine, but could not use 1,3-diaminopropane or cadaverine. Seven decarboxylated S-adenosylmethionine analogs were inhibitory to spermidine synthesis to varying degrees. Of these analogs, S-5′-deoxyadenosyl-(5′)-2-methylthioethylamine was the most potent inhibitor. Kinetic studies with some of the above compounds were also carried out.