3-Mercaptopropionic acid, a potent inhibitor of fatty acid oxidation in rat heart mitochondria.
The effects of several short-chain mercapto acids on the rate of respiration supported by either palmitoylcarnitine, octanoate, or pyruvate was studied with coupled rat heart mitochondria. 3-Mercaptopropionic acid was found to be a potent inhibitor of respiration sustained by palmitoylcarnitine or octanoate, whereas under identical conditions respiration with pyruvate as a substrate was unaffected. 2-Mercaptoacetic acid also inhibits palmitoylcarnitine-supported respiration, but only at much higher concentrations of the inhibitor. 2-Mercaptopropionic acid has virtually no effect. Incubation of mitochondria with 3-mercaptopropionic acid did not cause the irreversible inactivation of any beta-oxidation enzyme. Since 3-mercaptopropionic acid did not inhibit beta-oxidation in uncoupled mitochondria, it appears that this compound must first be metabolized in an energy-dependent reaction before it becomes inhibitory. 3-Mercaptopropionyl-CoA and three of its S-acyl derivatives, all of which are likely mitochondrial metabolites of 3-mercaptopropionic acid, were tested for their capacity to inhibit the individual enzymes of beta-oxidation. 3-Mercaptopropionyl-CoA inhibits only acyl-CoA dehydrogenase, whereas S-myristoyl-3-mercaptopropionyl-CoA inhibits reversibly several beta-oxidation enzymes. All observations together lead us to suggest that the inhibition of beta-oxidation by 3-mercaptopropionic acid in coupled rat heart mitochondria is most likely a consequence of the reversible inhibition of acyl-CoA dehydrogenase by long-chain S-acyl-3-mercaptopropionyl-CoA thioesters and possibly by 3-mercaptopropionyl-CoA.
D015097:3-Mercaptopropionic Acid / Q000494:pharmacology*; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000378:metabolism; D000818:Animals; D002210:Caprylates / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects*; D010172:Palmitoylcarnitine / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D002210:Caprylates; D005227:Fatty Acids; D011773:Pyruvates; D013438:Sulfhydryl Compounds; D010172:Palmitoylcarnitine; D015097:3-Mercaptopropionic Acid; D044942:Acyl-CoA Dehydrogenase, Long-Chain; C023884:thiolactic acid; C031492:octanoic acid