Comparison of inhibitors of S-adenosylmethionine decarboxylase from different species

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Abstract
S-Adenosyl-L-methionine decarboxylases were purified from rat ventral prostate, yeast (Saccharomyces cerevisiae), slime mold (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 analogs of S-adenosylmethionine with a different base were tested or when the ribose ring was opened or the positive charge on the S 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 betwen the enzymes from different sources. 5''-(Dimethylsufonio)-5''-deoxyadenosine and S-adenosyl-3-methylthiopropylamine were the most inhibitory substances and had similar Kki 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 analog, although the putrescine-activated enzymes from prostate and yeast were more sensitive than the bacterial and slime-mold enzymes. All of the S-adenoxylmethionine 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 relased by 1 mM concentrations of the drug, providing a rapid and efficient method for their purification.