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.