Effect of Dietary Protein on the Liver Content and Subunit Composition of the Branched-Chain α-Ketoacid Dehydrogenase Complex

Levels of expression of two subunits of the liver branched-chain α-ketoacid dehydrogenase complex in response to extremes of dietary protein intake (50% versus 0% protein diet) were determined by quantitative immunoblotting. Dietary protein deficiency decreased the amount of E1α protein to a greater extent than E2 protein. The ratio of E1α to E2 was below 1 in the liver of animals starved for protein and above 1 in the liver of animals fed the high-protein diet. Supplementation of the 0% protein diet with 5% leucine (but not 5% valine) had the same effect as the 50% protein diet. The extremes of dietary protein also resulted in a divergent pattern of expression of the mRNAs for the subunits of the complex. The E1β message showed the expected corollary of being greater in the liver of the high-protein-fed rats than the no-protein-fed rats. In contrast, the E2 message was not affected by the two extremes of dietary protein and the E1α message was greater in the liver of the no-protein-fed rats than the high-protein-fed rats. Thus, coordinate regulation of gene expression of the subunits of the complex does not occur in response to dietary protein. Post-transcriptional regulatory mechanisms most likely determine the amount of the complex and the ratio of its subunits. The decrease in E1α/E2 protein ratio that occurs in dietary protein deficiency may increase sensitivity of the complex to phosphorylation-mediated inhibition by branched-chain α-ketoacid dehydrogenase kinase.