Metabolism of lactate in the rat brain during the early neonatal period.
The metabolism of lactate in isolated cells from early neonatal rat brain has been studied. In these circumstances, lactate was mainly oxidized to CO2, although a significant portion was incorporated into lipids (78% sterols, 4% phosphatidylcholine, 2% phosphatidylethanolamine, and 1% phosphatidylserine). The rate of lactate incorporation into CO2 and lipids was higher than those found for glucose and 3-hydroxybutyrate. Lactate strongly inhibited glucose oxidation through the pyruvate dehydrogenase-catalyzed reaction and the tricarboxylic acid cycle while scarcely affecting glucose utilization by the pentose phosphate pathway. Lipogenesis from glucose was strongly inhibited by lactate without relevant changes in the rate of glycerol phosphate synthesis. These results suggest that lactate inhibits glucose utilization at the level of the pyruvate dehydrogenase-catalyzed reaction, which may be a mechanism to spare glucose for glycerol and NADPH synthesis. The effect of 3-hydroxybutyrate inhibiting lactate utilization only at high concentrations of 3-hydroxybutyrate suggests that before ketogenesis becomes active, lactate may be the major fuel for the neonatal brain. (-)-Hydroxycitrate and aminooxyacetate markedly inhibited lipogenesis from lactate, suggesting that the transfer of lactate carbons through the mitochondrial membrane is accomplished by the translocation of both citrate and N-acetylaspartate.
Vicario
C
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Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Salamanca, Spain.
Medina
J M
JM
D020155:3-Hydroxybutyric Acid; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002469:Cell Separation; D005947:Glucose / Q000378:metabolism; D006885:Hydroxybutyrates / Q000378:metabolism; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008928:Mitochondria / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D006885:Hydroxybutyrates; D007773:Lactates; D019344:Lactic Acid; D005947:Glucose; D020155:3-Hydroxybutyric Acid