In vivo C-13 NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during [2-C-13]glucose infusion

Journal article

The aims of this study were twofold: (i) to determine quantitatively the contribution of glutamate/glutamine cycling to total astrocyte/neuron substrate trafficking for the replenishment of neurotransmitter glutamate; and (ii) to determine the relative contributions of anaplerotic flux and glutamate/glutamine cycling to total glutamine synthesis. In this work in vivo and in vitro 13C NMR spectroscopy were used, with a [2-13C]glucose or [5-13C]glucose infusion, to determine the rates of glutamate/glutamine cycling, de novo glutamine synthesis via anaplerosis, and the neuronal and astrocytic tricarboxylic acid cycles in the rat cerebral cortex. The rate of glutamate/glutamine cycling measured in this study is compared with that determined from re-analysis of 13C NMR data acquired during a [1-13C]glucose infusion. The excellent agreement between these rates supports the hypothesis that glutamate/glutamine cycling is a major metabolic flux (∼0.20 μmol/min/g) in the cerebral cortex of anesthetized rats and the predominant pathway of astrocyte/neuron trafficking of neurotransmitter glutamate precursors. Under normoammonemic conditions anaplerosis was found to comprise 19-26% of the total glutamine synthesis, whilst this fraction increased significantly during hyperammonemia (∼32%). These findings indicate that anaplerotic glutamine synthesis is coupled to nitrogen removal from the brain (ammonia detoxification) under hyperammonemic conditions.

Authors: Sibson, N; Mason, G; Shen, J; Cline, G; Herskovits, A

• Publication status: Published
• Journal: JOURNAL OF NEUROCHEMISTRY
• Volume: 76
• Issue: 4
• Pages: 975-989
• Publication date: 2001-02-01
• DOI: 10.1046/j.1471-4159.2001.00074.x
• ISSN: 0022-3042
• Language: English
• Keywords: anaplerosis; neurotransmitter cycling; C-13 NMR; ammonia; glutamate; glutamine