Metabolism of 2-Oxo-Acid Analogues of Leucine and Valine in Isolated Rat Hepatocytes

Abstract

Isolated hepatocytes were incubated with l-14 C-labelled 2-oxo-acid analogues of leucine and valine. Decarboxylation and transamination rates were determined by measuring 14 C0 2 release and the appearance of the corresponding 14 C-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 branchedchain 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.

Alzheimer’s disease: targeting the glutamatergic system

“…Tracing studies of [ 15 N] leucine in rodent models showed that BCAAs were metabolised faster than they were incorporated into proteins in brain slices (Chaplin et al 1976). Approximately 30% of the nitrogen of Glu/glutamine was derived from leucine alone (Brand 1981;Brand and Hauschildt 1984), which was later supported using in vivo rat brain and ex vivo rat retina models (accepted models of Glutamatergic neurons) (Lieth et al 2001;LaNoue et al 2001). Based on the de novo synthesis of Glu from leucine, together with the location of BCATm in astrocytes and BCATc in neuronal cells, it was proposed that an exchange of metabolites between these cells, governed by BCAT transamination, supports Glu synthesis and regulation of the Glu/glutamine cycle (Yudkoff et al 1997;Hutson et al 1998;Hutson et al 2001).…”