Energy metabolism in rat brain: inhibition of pyruvate decarboxylation by 3-hydroxybutyrate in neonatal mitochondria.
The effect of 3-hydroxybutyrate on pyruvate decarboxylation by neonatal rat brain mitochondria and synaptosomes was investigated. The rate of [1-14C]pyruvate decarboxylation (1 mM final concentration) by brain synaptosomes derived from 8-day-old rats was inhibited by 10% in the presence of 2 mM-D,L-3-hydroxybutyrate and by more than 20% in the presence of 20 mM D,L-3-hydroxybutyrate. The presence of 2 mM-D,L-3-hydroxybutyrate did not affect the rate of [1-14C]pyruvate decarboxylation (1 mM final concentration) by brain mitochondria; however, at a concentration of 20 mM-D,L-3-hydroxybutyrate, a marked inhibition was seen in preparations from both 8-hydroxybutyrate, a marked inhibition was seen in preparations from both 8-day-old (35% inhibition) and 21-day-old (24% inhibition) but not in those from adult rats. Although the presence of 100 mM-K+ in the incubation medium stimulated the rate of pyruvate decarboxylation by approximately 50% compared with the rate in presence of 1 mM-K+, the presence of 20 mM-D,L-3-hydroxybutyrate still caused a marked inhibition in both media (1 and 100 mM-K+). The presence of 20 mM-D,L-3-hydroxybutyrate during the incubation caused an approximately 20% decrease in the level of the active form of the pyruvate dehydrogenase complex in brain mitochondria from 8-day-old rats. The concentrations of ATP, ADP, NAD+, NADH, acetyl CoA, and CoA were measured in brain mitochondria from 8-day-old rats incubated in the presence of 1 mM-pyruvate alone or 1 mM-pyruvate plus 20 mM-D,L-3-hydroxybutyrate. Neither the APT/ADP nor the NADH/NAD+ ratio showed significant changes. The acetyl CoA/CoA ratio was significantly increased by more than twofold in the presence of 3-hydroxybutyrate. The possible mechanisms and physiological significance of 3-hydroxybutyrate inhibition of pyruvate decarboxylation in neonatal rat brain rat mitochondria are discussed.
D020155:3-Hydroxybutyric Acid; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D006885:Hydroxybutyrates / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism
D006885:Hydroxybutyrates; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; D019289:Pyruvic Acid; D020155:3-Hydroxybutyric Acid