Differential distribution of the enzymes glutamate dehydrogenase and aspartate aminotransferase in cortical synaptic mitochondria contributes to metabolic compartmentation in cortical synaptic terminals

There have been numerous studies on the activity and localization of aspart ate aminotransferase (AAT) and glutamate dehydrogenase (GDH) in brain tissu e. However, there is still a controversy as to the specific roles and relat ive importance of these enzymes in glutamate and glutamine metabolism in as trocytes and neurons or synaptic terminals. There are many reports document ing GDH activity in synaptic terminals, yet the misconception that it is a glial enzyme persists. Furthermore, there is evidence that this tightly reg ulated enzyme may have an increased role in synaptic metabolism in adverse conditions such as low glucose and hyperammonemia that could compromise syn aptic function. In the present study, we report high activity of both AAT a nd GDH in mitochondrial subfractions from cortical synaptic terminals. The relative amount of GDH/AAT activity was higher in SM2 mitochondria, compare d to SMI mitochondria. Such a differential distribution of enzymes can cont ribute significantly to the compartmentation of metabolism. There is eviden ce that the metabolic capabilities of the SMI and SM2 subfractions of synap tic mitochondria are compatible with the compartments A and B of neuronal m etabolism proposed by Waagepetersen et al. (1998b. Dev. Neurosci. 20, 310-3 20). (C) 2000 Elsevier Science Ltd. All rights reserved.