title: 2-Mercaptoacetate administration depresses the beta-oxidation pathway through an inhibition of long-chain acyl-CoA dehydrogenase activity.
abstract: To elucidate the mechanisms through which 2-mercaptoacetate administration inhibits fatty acid oxidation in the liver, the respiration rates induced by different substrates were studied polarographically in rat hepatic mitochondria isolated 3 h after 2-mercaptoacetate administration. Palmitoyl-L-carnitine oxidation was almost completely inhibited in either the absence or presence of malonate. Octanoate oxidation was also inhibited, and the intramitochondrial acyl-CoA content was markedly increased. The oxidation rate of pyruvate and 2-oxoglutarate on the one hand and of 3-hydroxybutyrate, succinate and glutamate on the other was either normal or only slightly decreased. In the presence of 2,4-dinitrophenol, the extent of the inhibition of palmitoyl-L-carnitine oxidation was unchanged. All these results are consistent with the hypothesis that the 2-mercaptoacetate inhibition of fatty acid oxidation is due to an inhibition of the beta-oxidation pathway itself. Finally, the mitochondrial defect responsible for this inhibition was shown to be an inhibition of palmitoyl-CoA dehydrogenase activity (EC 1.3.99.3).
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000037:antagonists & inhibitors*; D000818:Animals; D005260:Female; D005292:Ferricyanides / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010172:Palmitoylcarnitine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013864:Thioglycolates / Q000494:pharmacology*
chemical_list: D005292:Ferricyanides; D013864:Thioglycolates; D010172:Palmitoylcarnitine; C017487:2-mercaptoacetate; D044942:Acyl-CoA Dehydrogenase, Long-Chain