Metabolism of 2-oxo-acid analogues of leucine and valine in isolated rat hepatocytes.

Isolated hepatocytes were incubated with 1-14C-labelled 2-oxo-acid analogues of leucine and valine. Decarboxylation and transamination rates were determined by measuring 14CO2 release and the appearance of the corresponding 14C-labelled amino acid. Decarboxylation exceeded transamination with both substrates, the ratio of decarboxylation/transamination being 3.4 for 4-methyl-2- oxovalerate and 78 for 3-methyl-2-oxobutyrate. Urea synthesis and ammonia utilization were not significantly decreased by the 2-oxo-acids even under conditions of stimulated urea production. To see if dietary treatment can alter the decarboxylation/ transamination ratio in favour of transamination rats were fed diets low in nitrogen content. These diets caused a reduction of the branched-chain 2-oxo-acid dehydrogenase activity by 80% but did not alter the branched-chain amino-acid aminotransferase activity in liver cells. This change in enzyme activities resulted in a marked decrease of the uptake and decarboxylation rates of 4-methyl-2- oxovalerate but did not enhance the conversion to the corresponding amino acid. Reducing the uptake of branched-chain 2-oxo acids by liver might increase the amount of orally administered 2-oxo acids reaching the muscle for transamination thus improving the nitrogen-sparing effect of these compounds.