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.

In the Human Malaria Parasite Plasmodium falciparum,Polyamines Are Synthesized by a Bifunctional Ornithine Decarboxylase,S-Adenosylmethionine Decarboxylase

“…The K m values of both enzyme activities were comparable to those of the AdoMetDC and ODC monofunctional proteins from mammals (32,46,57,58).…”

Mechanism of the inhibition of cell growth by N1, N12‐bis(ethyl)spermine

“…a-Difluoromethylornithine (F,MeOrn), an inhibitor of OrnDC [29], and ethylglyoxal bis(guany1hydrazone) (EGBG), an inhibitor of AdoMetDC [30,31], were kindly supplied by Marion Merrell Dow Inc. (Cincinnati, OH) and Nippon Carbide Industries, Inc. (Tokyo, Japan), respectively. Spermine tetrahydrochloride was purchased from Nacalai Tesque, Inc. (Kyoto, Japan).…”

Irreversible inhibition of putrescine-stimulated S-adenosyl-l-methionine decarboxylase by berenil and pentamidine

“…1), which is a potent reversible inhibitor of putrescine-stimulated ADC (Williams-Ashman & Schenone, 1972), present in higher eukaryotes (Poso et al, 1976), but not a good inhibitor of putrescine-insensitive ADC (Poso et al, 1975b;Pegg & Jacobs, 1983) or Mg2+-stimulated prokaryotic ADC. Pegg and co-workers have shown (Pegg & Conover, 1976;Pegg, 1978) that a derivative of MGBG, MBAG ( Fig.…”