Metabolism of branched-chain keto acids in neonatal rat liver perfusions

Abstract

The ability of the neonatal rat to oxidize the branched-chain amino acids leucine and valine and their corresponding keto acids was evaluated. In vivo, about 20% of orally administered labeled amino or keto acids were oxidized in 6 h, after which time little further oxidation occurred. In perfused neonatal liver the amino acids were oxidized at only 5–10% the rate of the keto acids. The oxidation of the keto acids showed a saturable dependence on concentration. The decarboxylation of ketoisocaproate (KIC) had a maximal rate of 40.1 ± 1.6 μmol/h/g liver with an apparent K m of 0.27 ± 0.03 m m and decarboxylation of ketoisovalerate (KIV) had a maximal rate of 37.9 ± 1.9 μmol/h/g liver and an apparent K m of 0.28 ± 0.04 m m. KIC was ketogenic, producing mainly acetoacetate at a maximal rate of 44.5 ± 1.6 μmol/h/g liver with an apparent K m of 0.27 ± 0.03 m m. On the other hand, KIV was not gluconeogenic, although the perfused neonatal liver was able to produce glucose from lactate. During liver perfusion, KIV did not produce measurable quantities of either propionic or β-aminoisobutyric acids, which are possible end products of KIV metabolism. Decanoic acid inhibited the decarboxylation of both keto acids to the same extent with a maximal effect at 0.4 m m fatty acid. At saturating levels, KIC was less ketogenic than decanoate. Inhibition of endogenous fatty acid oxidation by 2-tetradecylglycidic acid had no effect on keto acid oxidation. These data suggest that branched-chain amino acids derived from milk proteins are probably not quantitatively significant sources of either ketone bodies or glucose in the neonatal rat.