NAA in Neuronal Energy Metabolism

The first report that NAA might be involved in brain metabolism was by Buniatian and coworkers in 1965.18 The idea that NAA is involved in energy metabolism in the nervous system is based on a number of facts, including that 1) NAA is synthesized by aspartate N-acetyltransferase in neuronal mitochondria19,20, 2) traumatic brain injury causes rapid and partially reversible decreases in NAA concentrations,21-23 3) inhibition of mitochondrial respiration results in the simultaneous decrease of NAA production, ATP production and oxygen consumption in isolated brain mitochondria,24 and 4) NAA levels in the striatum of rats and primates were significantly decreased after the animals were treated with a mitochondrial toxin (3-ntiroproprionate).25 Recently, Madhavarao and coworkers proposed a model whereby NAA is associated with neuronal energy production (see Namboodiri et al. and Madhavarao and Namboodiri, this volume). In this model, aspartate aminotransferase, the enzyme that synthesizes NAA, facilitates removal of excess aspartate from neuronal mitochondria via acetylation, thus favoring a-ketoglutarate formation from glutamate, and energy production via the citric acid cycle.26

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