Fetal fuels. IV. Regulation of branched-chain amino and keto acid metabolism in fetal brain.
The regulation of branched-chain amino and keto acid metabolism was examined in fetal rat brains at 20 days gestation. When fetal brain slices were incubated with [1-14C]leucine, graded concentrations of beta-hydroxybutyrate or acetoacetate resulted in a progressive rise in labeled alpha-ketoisocaproic acid accompanied by a fall in 14CO2, whereas the sum of these products remained unchanged. These reciprocal relationships were maintained when leucine concentrations were varied from 0.4 to 4 mM. Increasing concentrations of glucose or pyruvate enhanced the formation of both 14CO2 and alpha-ketoisocaproic acid from [1-14C]leucine, but resulted in a progressive decrease in the conversion of alpha-ketoisocaproic acid to 14CO2. That glucose and ketone bodies probably acted via separate mechanisms was suggested by a further inhibition of alpha-ketoisocaproic acid decarboxylation whenever beta-hydroxybutyrate was added. When mothers were starved from days 18-20, a threefold rise in circulating branched-chain keto acids was reflected concordantly in the fetus and was attended by a significant enhancement of leucine transaminase activity in fetal brain. Because levels of circulating ketone bodies reported during maternal starvation were maximally effective in diminishing the conversion of alpha-ketoisocaproic acid to 14CO4, it is suggested that the inhibitory effects of beta-hydroxybutyrate on the critical dehydrogenase step in branched-chain keto acid metabolism in fetal brain could restrain oxidation of maternally derived alpha-ketoisocaproic acid, thereby permitting salvage for reversible transamination to leucine.
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates; D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006885:Hydroxybutyrates / Q000378:metabolism*; D007651:Keto Acids / Q000378:metabolism*; D007700:Kinetics; D007930:Leucine / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013217:Starvation
D000090:Acetoacetates; D006885:Hydroxybutyrates; D007651:Keto Acids; C016635:acetoacetic acid; D007930:Leucine; D020155:3-Hydroxybutyric Acid