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Rat brain slices oxidize glucose at high rates: a (13)C NMR study
Authors:El Hage Maha  Ferrier Bernard  Baverel Gabriel  Martin Guy
Institution:a Institut National de la Santé et de la Recherche Médicale, Unit # 820 (Métabolomique et Maladies Métaboliques), 69372 Lyon Cedex 08, France
b Metabolys Inc., Faculté de Médecine R.T.H. Laennec, 69372 Lyon Cedex 08, France
Abstract:Since glucose is the main cerebral substrate, we have characterized the metabolism of various 13C glucose isotopomers in rat brain slices. For this, we have used our cellular metabolomic approach that combines enzymatic and carbon 13 NMR techniques with mathematical models of metabolic pathways. We identified the fate and the pathways of the conversion of glucose carbons into various products (pyruvate, lactate, alanine, aspartate, glutamate, GABA, glutamine and CO2) and determined absolute fluxes through pathways of glucose metabolism. After 60 min of incubation, lactate and CO2 were the main end-products of the metabolism of glucose which was avidly metabolized by the slices. Lactate was also used at high rates by the slices and mainly converted into CO2. High values of flux through pyruvate carboxylase, which were similar with glucose and lactate as substrate, were observed. The addition of glutamine, but not of acetate, stimulated pyruvate carboxylation, the conversion of glutamate into succinate and fluxes through succinate dehydrogenase, malic enzyme, glutamine synthetase and aspartate aminotransferase. It is concluded that, unlike brain cells in culture, and consistent with high fluxes through PDH and enzymes of the tricarboxylic acid cycle, rat brain slices oxidized both glucose and lactate at high rates.
Keywords:13C NMR  Brain slices  Glucose  Lactate  Metabolism
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