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Metabolic Fate of a High Concentration of Glutamine and Glutamate in Rat Brain Slices: a (13)C NMR Study.
MedLine Citation:
PMID:  21338644     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
This study was performed to analyze the metabolic fate of a high concentration (5mM) of glutamine and glutamate in rat brain slices and the participation of these amino acids in the glutamine-glutamate cycle. For this, brain slices were incubated for 60min with [3-(13)C]glutamine or [3-(13)C]glutamate. Tissue plus medium extracts were analyzed by enzymatic and (13)C NMR measurements and fluxes through pathways of glutamine and glutamate metabolism were calculated. We demonstrate that both substrates were utilized and oxidized at high rates by rat brain slices and served as precursors of neurotransmitters, tricarboxylic acid (TCA) cycle intermediates and alanine. In order to determine the participation of glutamine synthetase in the appearance of new glutamine molecules with glutamine as substrate, brain slices were incubated with [3-(13)C]glutamine in the presence of methionine sulfoximine, a specific inhibitor of glutamine synthetase. Our results indicate that 36.5% of the new glutamine appeared was glutamine synthetase- dependent and 63.5% was formed from endogenous substrates. Flux through glutamic acid decarboxylase was higher with glutamine than with glutamate as substrate whereas fluxes from α-ketoglutarate to glutamate and through glutamine synthetase, malic enzyme, pyruvate dehydrogenase, pyruvate carboxylase and citrate synthase were in the same range with both substrates.
Authors:
Maha El Hage; Agnès Conjard-Duplany; Gabriel Baverel; Guy Martin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-18
Journal Detail:
Title:  Neurochemistry international     Volume:  -     ISSN:  1872-9754     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Ltd.
Affiliation:
Institut National de la Santé et de la Recherche Médicale, Unit # 820, (Métabolomique et Maladies Métaboliques); Metabolys, Inc., Faculté de Médecine R.T.H. Laennec, 69372 Lyon Cedex 08, France.
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