Developmental pattern of branched-chain 2-oxo acid dehydrogenase complex in rat liver and heart

Abstract

The developmental pattern of the branched-chain 2-oxo acid dehydrogenase complex was examined in the liver and heart of the rat throughout the suckling period. Basal activity and total activity of the complex were measured as a function of age. The hepatic enzyme activity increased dramatically and was 100% active (dephosphorylated) during the suckling period. The level of protein kinase associated with the complex was particularly low at birth, but like the complex increased throughout the suckling period. The level of heart enzyme also increased as a function of age, but only about 30-45% of the enzyme was active throughout the suckling period. Very low protein levels of liver and heart branched-chain 2-oxo acid dehydrogenase were detected by immunoblot analysis in newborn rats. The mRNA levels for the liver E1 alpha, E1 beta, and E2 subunits in newborn rat were 30%, 19%, and 4% of adult levels respectively. The capacity of the neonatal rat for oxidizing leucine in vivo was low at birth and increased with age. 4-Methyl-2-oxopentanoate was more toxic when given to newborn and 3-day-old pups than 21-day-old pups, as expected from the relative capacities of their tissues to dispose of branched-chain 2-oxo acids by oxidation. Force-feeding suckling rats a protein-free artificial milk formula resulted in partial inactivation of the hepatic branched-chain 2-oxo acid dehydrogenase complex, indicating that the liver of the suckling rat can adapt to conserve branched-chain amino acid residues during periods of protein deficiency.