title: In vivo (13)C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during.
abstract: 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.
authors.affiliation: Departments of Molecular Biophysics, Yale University School of Medicine, New Haven, Connecticut, USA. niki@bioch.ox.ac.uk
authors.forename: N R
authors.initials: NR
authors.lastname: Sibson
authors.forename: G F
authors.initials: GF
authors.lastname: Mason
authors.forename: J
authors.initials: J
authors.lastname: Shen
authors.forename: G W
authors.initials: GW
authors.lastname: Cline
authors.forename: A Z
authors.initials: AZ
authors.lastname: Herskovits
authors.forename: J E
authors.initials: JE
authors.lastname: Wall
authors.forename: K L
authors.initials: KL
authors.lastname: Behar
authors.forename: D L
authors.initials: DL
authors.lastname: Rothman
authors.forename: R G
authors.initials: RG
authors.lastname: Shulman
mesh_terms: D000085:Acetates; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001786:Blood Glucose; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology; D002247:Carbon Isotopes; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism; D002952:Citric Acid Cycle / Q000502:physiology*; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D022124:Hyperammonemia / Q000139:chemically induced / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008962:Models, Theoretical; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000085:Acetates; D001786:Blood Glucose; D002247:Carbon Isotopes; D005973:Glutamine; D018698:Glutamic Acid; D000641:Ammonia; D005947:Glucose; C018824:ammonium acetate