[Depression of rat liver acetyl-CoA-carboxylase activity by salicylate and other compounds].
Two intraperitoneal injections of salicylate at a dose of 250 mg/kg of body weight led to decrease in the acetyl-CoA-carboxylase activity in liver soluble fraction (140000xg) more than by 60%. Salicylate in concentrations 10(-4) and 10(-2) M inhibited the enzyme from rat liver soluble fraction by 25% and 80%, respectively, in vitro: it was found to be as effective inhibitor as kynurenate and clofibrate. Derivatives of salicylate -- acetyl salicylate and salicyl amide also showed this inhibitory effect, but their action was less disinct as compared with salicylate. 2-phenyl-3-methyl-hydroxypentanic and 2,3-diphenyl-3-hydroxypentanic acids (derivatives of deoxymevalonic acid) demonstrated the strong inhibitory effect on acetyl-CoA-carboxylase, comparable to the action of salicylate. The effect of salicylate on the reaction of carboxylation was not related to competition for acetyl-CoA (formation of acetyl salicylate), to interaction with biotin and to allosteric reaction with acetyl-CoA-carboxylase. Possible mechanisms of the salicylate effect on the enzyme activity are discussed.
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D000107:Acetylation; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002994:Clofibrate / Q000494:pharmacology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D008025:Ligases / Q000037:antagonists & inhibitors*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D012457:Salicylamides / Q000494:pharmacology; D012459:Salicylates / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D004791:Enzyme Inhibitors; D012457:Salicylamides; D012459:Salicylates; D008025:Ligases; D000103:Acetyl-CoA Carboxylase; D007736:Kynurenic Acid; D002994:Clofibrate; D001241:Aspirin
Ugnetenie salitsilatom i nekotorymi drugimi soedineniiami aktivnosti atsetil-KoA-karboksilazy pecheni krys.