Acute Action of Ammonia on Leucine Metabolism in Isolated Astrocytes, Neurons and Oligo Cells of Rat Brain

Abstract

It is well known that in brain ammonia is detoxified by way of glutamine synthesis and this process requires glutamate as a precursor (Cooper et al., 1979, 1985; Cooper and Plum, 1987). Results obtained in the studies on metabolic compartmentation led to the belief that the glutamate required for this process is generated in the astrocytes by the reductive amination of α-ketoglutarate (KG) in the reaction mediated by glutamate dehydrogenase (Berl and Clarke, 1983). However, it was observed recently that the glutamate generated in this reaction may not be serving as the substrate for the synthesis of glutamine in brain either in normal or in hyper-ammonemic states (Cooper et al., 1979, 1985; Subbalakshmi and Murthy, 1983; Yudkoff et al., 1983; Yu et al., 1984). Hence, it was proposed that the pool of glutamate required for glutamine synthesis in brain may be generated from the transamination of branched-chain amino acids (leucine, isoleu-cine and valine; BCAA) with KG (Cooper et al., 1979, 1985; Duffy and Plum, 1982; Jessy and Murthy, 1985, 1988).