Inhibition of S-adenosylmethionine decarboxylase and diamine oxidase activities by analogues of methylglyoxal bis(guanylhydrazone) and their cellular uptake during lymphocyte activation.
Several congeners of methylglyoxal bis(guanylhydrazone) were tested for their ability to inhibit eukaryotic putrescine-activated S-adenosylmethionine decarboxylase (EC 4.1.1.50) and intestinal diamine oxidase (EC 1.4.3.6). All the compounds tested, namely methylglyoxal bis(guanylhydrazone), ethylglyoxal bis(guanylhydrazone), dimethylglyoxal bis(guanylhydrazone) and the di-N"-methyl derivative of methylglyoxal bis(guanylhydrazone), were strong inhibitors of both yeast and mouse liver adenosylmethionine decarboxylase activity in vitro. The enzyme from both sources was most powerfully inhibited by ethylglyoxal bis(guanylhydrazone). All the diguanidines likewise inhibited diamine oxidase activity in vitro. The maximum intracellular concentrations of the ethyl and dimethylated analogues achieved in activated lymphocytes were only about one-fifth of that of the parent compound. However, both derivatives appeared to utilize the polyamine-carrier system, as indicated by competition experiments with spermidine.
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors*; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors*; D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D002417:Cattle; D002478:Cells, Cultured; D006146:Guanidines / Q000494:pharmacology*; D007422:Intestines / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008935:Mitoguazone / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology
D006146:Guanidines; C021998:dimethylglyoxal bis(guanylhydrazone); C041127:ethylglyoxal bis(guanylhydrazone); C021999:di-N',N''-methylglyoxal bis(guanylhydrazone); D006631:Amine Oxidase (Copper-Containing); D002262:Carboxy-Lyases; D012437:Adenosylmethionine Decarboxylase; D008935:Mitoguazone