Brain metabolism of exogenous pyruvate.

作者: Susana Villa Gonzalez , Nga H. T. Nguyen , Frode Rise , Bjørnar Hassel

DOI: 10.1111/J.1471-4159.2005.03365.X

关键词:

摘要: Pyruvate given in large doses may be neuroprotective stroke, but it is not known to what degree the brain metabolizes pyruvate. Intravenous injection of [3-13C]pyruvate led dose-dependent labelling cerebral metabolites so that at 5 min after 18 mmoles [3-13C]pyruvate/kg (2 g sodium pyruvate/kg), approximately 20% glutamate and GABA were labelled, as could detected by 13C nuclear magnetic resonance spectrometry ex vivo. Pyruvate, 9 mmoles/kg, was equivalent glucose, a substrate for tricarboxylic acid (TCA) cycle activity. Inhibition glial TCA with fluoroacetate did affect formation [4-13C]glutamate or [2-13C]GABA from [3-13C]pyruvate, reduced [4-13C]glutamine 50%, indicating predominantly neuronal metabolism exogenous Extensive [3-13C]lactate [2-13C]pyruvate demonstrated reversible carboxylation pyruvate malate equilibration fumarate, presumably neurones, anaplerotic intermediates detected. Too rapid amounts seizure activity, respiratory arrest death. We conclude an excellent energy neurones vivo, care must taken avoid seizure-inducing effect doses.

参考文章(43)
Helle S. Waagepetersen, Hong Qu, Leif Hertz, Ursula Sonnewald, Arne Schousboe, Demonstration of pyruvate recycling in primary cultures of neocortical astrocytes but not in neurons. Neurochemical Research. ,vol. 27, pp. 1431- 1437 ,(2002) , 10.1023/A:1021636102735
J. W. Pan, F. W. Telang, J. H. Lee, R. A. De Graaf, D. L. Rothman, D. T. Stein, H. P. Hetherington, Measurement of β-hydroxybutyrate in acute hyperketonemia in human brain Journal of Neurochemistry. ,vol. 79, pp. 539- 544 ,(2008) , 10.1046/J.1471-4159.2001.00575.X
Bjørnar Hassel, Anders Bråthe, Cerebral metabolism of lactate in vivo: evidence for neuronal pyruvate carboxylation. Journal of Cerebral Blood Flow and Metabolism. ,vol. 20, pp. 327- 336 ,(2000) , 10.1097/00004647-200002000-00014
Rudolph A. Peters, Mechanism of the toxicity of the active constituent of Dichapetalum cymosum and related compounds. Advances in Enzymology and Related Areas of Molecular Biology, Volume 18. ,vol. 18, pp. 113- 159 ,(1957) , 10.1002/9780470122631.CH3
S Cerdan, B Künnecke, J Seelig, Cerebral metabolism of [1,2-13C2]acetate as detected by in vivo and in vitro 13C NMR. Journal of Biological Chemistry. ,vol. 265, pp. 12916- 12926 ,(1990) , 10.1016/S0021-9258(19)38247-X
Nga Huynh Tran Nguyen, Anders Bråthe, Bjørnar Hassel, Neuronal uptake and metabolism of glycerol and the neuronal expression of mitochondrial glycerol-3-phosphate dehydrogenase Journal of Neurochemistry. ,vol. 85, pp. 831- 842 ,(2003) , 10.1046/J.1471-4159.2003.01762.X
Nelson D. Goldberg, Janet V. Passonneau, Oliver H. Lowry, Effects of Changes in Brain Metabolism on the Levels of Citric Acid Cycle Intermediates Journal of Biological Chemistry. ,vol. 241, pp. 3997- 4003 ,(1966) , 10.1016/S0021-9258(18)99802-9
John H. Exton, Jerry G. Corbin, Sandra C. Harper, Control of Gluconeogenesis in Liver Journal of Biological Chemistry. ,vol. 247, pp. 4996- 5003 ,(1972) , 10.1016/S0021-9258(19)44930-2
Jed A. Hartings, Michael L. Rolli, X.-C. May Lu, Frank C. Tortella, Delayed secondary phase of peri-infarct depolarizations after focal cerebral ischemia: relation to infarct growth and neuroprotection. The Journal of Neuroscience. ,vol. 23, pp. 11602- 11610 ,(2003) , 10.1523/JNEUROSCI.23-37-11602.2003