期刊
JOURNAL OF NEUROCHEMISTRY
卷 76, 期 4, 页码 975-989出版社
BLACKWELL SCIENCE LTD
DOI: 10.1046/j.1471-4159.2001.00074.x
关键词
ammonia; anaplerosis; C-13 NMR; glutamate; glutamine; neurotransmitter cycling
资金
- NICHD NIH HHS [P01 HD032573, HD-32573] Funding Source: Medline
- NIDDK NIH HHS [R01 DK027121, DK-27121] Funding Source: Medline
- NINDS NIH HHS [R01 NS034813, NS-32126] Funding Source: Medline
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 C-13 NMR spectroscopy were used, with a [2-C-13]glucose or [5-C-13]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 C-13 NMR data acquired during a [1-C-13]glucose infusion. The excellent agreement between these rates supports the hypothesis that glutamate/glutamine cycling is a major metabolic flux (similar to0.20 mu mol/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 (similar to 32%). These findings indicate that anaplerotic glutamine synthesis is coupled to nitrogen removal from the brain (ammonia detoxification) under hyperammonemic conditions.
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