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In vivo 13 C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during [2‐ 13 C]glucose infusion
Author(s) -
Sibson Nicola R.,
Mason Graeme F.,
Shen Jun,
Cline Gary W.,
Herskovits A. Zara,
Wall Joyce E. M.,
Behar Kevin L.,
Rothman Douglas L.,
Shulman Robert G.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00074.x
Subject(s) - glutamine , glutamate receptor , astrocyte , hyperammonemia , biochemistry , glutamic acid , citric acid cycle , neurotransmitter , biology , chemistry , metabolism , endocrinology , amino acid , central nervous system , receptor
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 13 C NMR spectroscopy were used, with a [2‐ 13 C]glucose or [5‐ 13 C]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 13 C NMR data acquired during a [1‐ 13 C]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.