Inhibition of fatty acid oxidation by 2-bromooctanoate. Evidence for the enzymatic formation of 2-bromo-3-ketooctanoyl coenzyme A and the inhibition of 3-ketothiolase.
Incubation of rat liver mitochondria with 10 microM DL-2-bromooctanoate causes complete and irreversible inactivation of 3-ketothiolase I (acyl-CoA:acetyl-CoA C-acyltransferase). Evidence is presented that mitochondria convert bromooctanoate to 2-bromo-3-ketooctanoyl-CoA, an alpha-haloketone which is probably the active form of the inhibitor. The inactivation is accompanied by incorporation of radioactivity from [1-14C]bromooctanoate into the enzyme. Bromooctanoate does not affect the activities of the other enzymes of beta-oxidation, except for 3-ketothiolase II (acetyl-CoA:acetyl-CoA C-acetyltransferase), which becomes partially inhibited. Evidence is also presented that various enzymes of beta-oxidation can use 2-bromooctanoyl-CoA and its beta-oxidation products as substrates.
D000102:Acetyl-CoA C-Acyltransferase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D000214:Acyl Coenzyme A; D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D002210:Caprylates / Q000494:pharmacology*; D007700:Kinetics; D008930:Mitochondria, Liver / Q000201:enzymology*; D008970:Molecular Weight; D051381:Rats
D000214:Acyl Coenzyme A; D002210:Caprylates; D000217:Acyltransferases; D000102:Acetyl-CoA C-Acyltransferase