In vivo (13)C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during

J Neurochem. 2001 Feb;76(4):975-89. doi: 10.1046/j.1471-4159.2001.00074.x.


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 ( approximately 0.20 micromol/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 ( approximately 32%). These findings indicate that anaplerotic glutamine synthesis is coupled to nitrogen removal from the brain (ammonia detoxification) under hyperammonemic conditions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetates
  • Ammonia / metabolism
  • Animals
  • Astrocytes / metabolism
  • Blood Glucose
  • Brain / cytology
  • Brain / metabolism*
  • Brain Chemistry / physiology
  • Carbon Isotopes
  • Cerebral Cortex / chemistry
  • Cerebral Cortex / metabolism
  • Citric Acid Cycle / physiology*
  • Glucose / administration & dosage
  • Glucose / metabolism*
  • Glutamic Acid / metabolism*
  • Glutamine / metabolism
  • Homeostasis / physiology
  • Hyperammonemia / chemically induced
  • Hyperammonemia / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Models, Theoretical
  • Neurons / metabolism
  • Rats
  • Rats, Sprague-Dawley


  • Acetates
  • Blood Glucose
  • Carbon Isotopes
  • Glutamine
  • Glutamic Acid
  • Ammonia
  • Glucose
  • ammonium acetate