Compartmentation of Tricarboxylic Acid Cycle Intermediates and Related Metabolites

Abstract

The first suggestion of metabolic compartmentation in the brain was obtained by the late Dr Heinrich Waelsch and his associates while studying glutamate metabolism (Lajtha et al., 1960). This was further substantiated by the intra-carotid infusion of [¹⁵N]ammonia or [¹⁴C]bicarbonate (Berl et al., 1962a,b). The specific radioactivity was found to be highest in glutamine, suggesting that glutamine was synthesized from an extremely active glutamate pool of relatively small size in the brain. Since the only known metabolic reaction leading to the synthesis of glutamine is that catalyzed by glutamine synthetase, it was proposed that both glutamate and glutamine exist in two separate pools. The observations made originally in vivo were later confirmed in in vitro studies using brain slices (Balázs et al., 1970; Berl and Clarke, 1969; Berl et al., 1970; Cheng and Nakamura, 1972; Nakamura and Cheng, 1969; Nakamura et al., 1970; Simon et al., 1967; 1968).