Fetal fuels VI. Metabolism of alpha-ketoisocaproic acid in fetal rat brain.

The metabolic regulation of alpha-ketoisocaproic acid was studied in fetal brain from rats. Starvation of the mother for days 18-20 did not alter CO2 evolution from alpha-ketoisocaproic acid in fetal brain slices but significantly diminished the incorporation of the branched-chain keto acids into leucine. When fetal brain slices from starved mothers were exposed to graded concentrations of labeled alpha-ketoisocaproic acid (0.05-2.5 mM), over 70% of the labeled products were consistently represented by leucine and less than 30% by CO2. Both beta-hydroxybutyrate and pyruvate, alone and in combination, diminished the amount of 14CO2 that evolved from alpha-ketoisocaproic acid-1-14C, but had no effect on the conversion of the keto acid to labeled leucine. It is concluded that exogenous alpha-ketoisocaproic acid is preferentially converted to leucine by fetal brain slices independent of the nutritional state of the mother. During maternal starvation, beta-hydroxybutyrate, by restraining irreversible decarboxylation of alpha-ketoisocaproic acid, could act to salvage the keto acid for conversion to leucine. Thus alpha-ketoisocaproic acid metabolism in the fetal brain may be regulated in part by altered metabolic functions in this structure and in part by changing components in circulating fuel mixtures reaching the fetus from the starved mother.