Inhibition of adenosylmethionine decarboxylase and perturbation of polyamine metabolism by 3-deaza-(+/-)aristeromycin.
3-Deaza-(+/-)aristeromycin, previously known mainly as a potent inhibitor of adenosylhomocysteine hydrolase, can also inhibit the activity of adenosylmethionine decarboxylase. The release of [14C]CO2 from HeLa cells labeled with [carboxyl-14C]methionine was inhibited by more than 70% after 4 hours in the presence of 4 microM 3-deaza-(+/-)aristeromycin. Concomitant with this inhibition, there was a significant increase in the amount of putrescine in the HeLa cells. Adenosylmethionine decarboxylase isolated from HeLa cells could also be inhibited by 3-deaza-(+/-)aristeromycin and 3-deazaadenosine, 3-deazaadenosylhomocysteine, and 3-deaza-(+/-)aristeromycinylhomocysteine.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D011073:Polyamines / Q000378:metabolism*
D004791:Enzyme Inhibitors; D011073:Polyamines; C034583:3-deazaaristeromycin; D002262:Carboxy-Lyases; D012437:Adenosylmethionine Decarboxylase; D000241:Adenosine