INHIBITORY EFFECTS OF ACYL-COENZYME A ESTERS ON PYRUVATE AND ALPHA-OXOGLUTARATE DEHYDROGENASE COMPLEXES

1. 1. Acyl-CoA inhibition of the pyruvate and α-oxoglutarate dehydrogenase complexes was studied in order to gain some insight into possible factors which might regulate these two enzymes. 2. 2. Short chain acyl-CoA esters inhibit the overall pyruvate and α-oxoglutarate dehydrogenase complex by competing for the CoASH site. The efficiency with which CoASH overcomes this inhibition in the two complexes is a function of the Km for CoASH of the two enzymes. 3. 3. Long chain acyl-CoA inhibition of α-oxoglutarate dehydrogenase was studied in detail. Inhibition results from irreversible binding of acyl-CoA to the CoASH site by virtue of the interaction between the acyl-CoA side chain with hydrophobic regions in the enzyme. The potency of this inhibition is related to the properties of the acyl side chain. 4. 4. The interaction between hydrocarbon side chain of acyl-CoA esters and the intact α-oxoglutarate dehydrogenase ultimately results in the dissociation of lipoamide dehydrogenase from the complex. 5. 5. Control of α-oxo acid oxidation is considered to be related to short chain acyl-CoA and free CoASH levels rather than to inhibition by long chain acyl-CoA esters. © 1969.