title: Comparison of inhibitors of S-adenosylmethionine decarboxylase from different species.
abstract: S-Adenosyl-L-methionine decarboxylases were purified from rat ventral prostate, yeast (Saccharomyces cerevisiae), slime mould (Physarum polycephalum) and bacteria (Escherichia coli) and tested for inhibition by a variety of nucleosides related to S-adenosylmethionine and by methyl- and ethyl-glyoxal bis(guanylhydrazone). Although the enzymes from these different sources are markedly different with respect to activation by cations, the inhibition by nucleosides was quite similar. Very little inhibition was seen when analogues of S-adenosylmethionine with a different base were tested or when the ribose ring was opened or the positive charge on the sulphur atom was not present. Some derivatives in which the amino acid portion of the molecule was altered were more potent inhibitors, but again there was little difference between the enzymes from different sources. 5'-(Dimethylsulphonio)-5'-deoxyadenosine and S-adenosyl-3-methylthiopropylamine were the most inhibitory substances and had similar Ki values, suggesting that the aminopropyl group does not contribute significantly to the binding. All of the S-adenosylmethionine decarboxylases were strongly competitively inhibited by methylglyoxal bis(guanylhydrazone) and even more powerfully by its ethyl analogue, although the putrescine-activated enzymes from prostate and yeast were more sensitive than the bacterial and slime-mould enzymes. All of the S-adenosylmethionine decarboxylases tested bound to a column of methylglyoxal bis(guanylhydrazone) linked to Sepharose and were not eluted by 0.5 M-NaCl, but could be released by 1 mM concentrations of the drug, providing a rapid and efficient method for their purification.
mesh_terms: D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors*; D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000201:enzymology; D006835:Hydrazones / Q000494:pharmacology; D008297:Male; D010804:Physarum / Q000201:enzymology; D011467:Prostate / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D012436:S-Adenosylmethionine / Q000031:analogs & derivatives / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D006835:Hydrazones; D012436:S-Adenosylmethionine; D002262:Carboxy-Lyases; D012437:Adenosylmethionine Decarboxylase