Pyruvate carboxylation in neurons

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 o f the glutamine cycle. It was shown recently, however, that carboxylation o f pyruvate to malate occurs in neurons and that it supports formation of tr ansmitter glutamate. The role of pyruvate carboxylation in neurons is to en sure tricarboxylic acid cycle activity by compensating for losses of alpha -ketoglutarate that occur through release of transmitter glutamate and GABA ; these amino acids are a-ketoglutarate derivatives. Available data suggest that neuronal pyruvate carboxylation is quantitatively important. But beca use there is no net CO2 fixation in the brain, pyruvate carboxylation must be balanced by decarboxylation of malate or oxaloacetate. Such decarboxylat ion occurs in both neurons and astrocytes. Several in vitro studies have sh own a neuroprotective effect of pyruvate supplementation. Pyruvate carboxyl ation may be one mechanism through which such treatment is effective, becau se pyruvate carboxylation through malic enzyme is active during energy defi ciency and leads to an increase in the level of dicarboxylates that can be metabolized through the tricarboxylic acid cycle for ATP production. (C) 20 01 Wiley-Liss, Inc.