2-MERCAPTOACETATE ADMINISTRATION DEPRESSES THE BETA-OXIDATION PATHWAY THROUGH AN INHIBITION OF LONG-CHAIN ACYL-COA DEHYDROGENASE-ACTIVITY

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 and of 3-hydroxybutyrate, succinate and glutamate 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. The mitochondrial defect responsible for this inhibition was an inhibition of palmitoyl-CoA dehydrogenase activity (EC 1.3.99.3).