MECHANISM OF ACTIVATION OF SOLUBLE GUANYLATE-CYCLASE BY GUANIDINE THIOLS - A NEW CLASS OF ENZYME ACTIVATORS

The study is concerned with the mechanism of activation of soluble gua nylate cycla-se by guanidine thiol derivatives a new class of enzyme a ctivators. Guanidine thiols contain both the guanidine and SH group wh ich act, respectively, as donor and acceptor of nitric bride (NO). The role of guanidine thiol SH group in the mechanism of soluble guanylat e cyclase activation was studied. Three guanidine thiol derivatives we re tested: mercaptoethylguanidine, its disulfide and S-methyl mercapto ethylguani-dine. All three compounds proved to be NO-synthase substrat es and, simultaneously, guanylate cyclase activators. The degrees of g uanylate cyclase activation by mercaptoethylguanidine and its disulfid e were, respectively, two and four times higher than that by L-arginin e. The stimulatory effects of S-methyl mercaptoethylguanidine and L-ar ginine were evaluated and found to be of the same order. The important role of S-acceptor group of guanidine thiols in the mechanism of guan ylate cyclase activation increase provides an explanation for differen t intensities of guanylate cyclase activation by the compounds tested. NO-acceptor properties of guanidine thiols disulfide bonds in the syn thase mechanism of NO generation were first reported.