Irreversible inhibition of putrescine-stimulated S-adenosyl-L-methionine decarboxylase by berenil and pentamidine.
The putrescine-stimulated S-adenosyl-L-methionine decarboxylases from rat liver and yeast were strongly inhibited by Berenil and to a lesser extent by Pentamidine. Ten times greater drug concentrations were needed to achieve a similar level of inhibition of a Mg2+-stimulated bacterial enzyme. The inhibition was irreversible in that extensive dialyses or precipitation with (NH4)2SO4 did not restore enzyme activity. Putrescine did not protect the enzyme against Berenil, but adenosylmethionine either alone or with putrescine partially protected the irreversible action of Berenil. The compound 4,4'-diamidinodiphenylamine, which differs from Berenil only in lacking the azo group between benzene rings, was a weaker inhibitor than Berenil, and its inhibition was reversible. Berenil also inhibited the activity of adenosylmethionine decarboxylase in vivo, by depressing the activity of the enzyme in normal rat liver, for at least 24 h after a single injection (50 mg/kg body wt.) of the drug.
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors*; D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D004133:Diminazene / Q000031:analogs & derivatives / Q000494:pharmacology*; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D010419:Pentamidine / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000201:enzymology; D011700:Putrescine / Q000494:pharmacology*; D051381:Rats; D012436:S-Adenosylmethionine / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000201:enzymology
D000578:Amidines; C046869:4,4'-diamidinodiphenylamine; D010419:Pentamidine; D012436:S-Adenosylmethionine; D004159:Diphenylamine; D002262:Carboxy-Lyases; D012437:Adenosylmethionine Decarboxylase; C003915:diminazene aceturate; D011700:Putrescine; D004133:Diminazene