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Pyruvate carboxylation in neurons
Author(s) -
Hassel Bjørnar
Publication year - 2001
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10044
Subject(s) - carboxylation , citric acid cycle , pyruvate carboxylase , pyruvate decarboxylation , biochemistry , pyruvate dehydrogenase complex , decarboxylation , tricarboxylic acid , chemistry , glutamate receptor , pyruvate dehydrogenase phosphatase , pyruvate dehydrogenase kinase , gluconeogenesis , glutamine , pyruvic acid , metabolism , amino acid , enzyme , catalysis , receptor
Carboxylation of pyruvate in the brain was for many years thought to occur only in glia, an assumption that formed much of the basis for the concept of the glutamine cycle. It was shown recently, however, that carboxylation of pyruvate to malate occurs in neurons and that it supports formation of transmitter glutamate. The role of pyruvate carboxylation in neurons is to ensure tricarboxylic acid cycle activity by compensating for losses of α‐ketoglutarate that occur through release of transmitter glutamate and GABA; these amino acids are α‐ketoglutarate derivatives. Available data suggest that neuronal pyruvate carboxylation is quantitatively important. But because there is no net CO 2 fixation in the brain, pyruvate carboxylation must be balanced by decarboxylation of malate or oxaloacetate. Such decarboxylation occurs in both neurons and astrocytes. Several in vitro studies have shown a neuroprotective effect of pyruvate supplementation. Pyruvate carboxylation may be one mechanism through which such treatment is effective, because pyruvate carboxylation through malic enzyme is active during energy deficiency and leads to an increase in the level of dicarboxylates that can be metabolized through the tricarboxylic acid cycle for ATP production. © 2001 Wiley‐Liss, Inc.