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Brain metabolism of exogenous pyruvate
Author(s) -
Gonzalez Susana Villa,
Nguyen Nga H. T.,
Rise Frode,
Hassel Bjørnar
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03365.x
Subject(s) - citric acid cycle , fluoroacetate , pyruvate decarboxylation , pyruvate carboxylase , pyruvate dehydrogenase complex , dihydrolipoyl transacetylase , sodium pyruvate , pyruvate dehydrogenase kinase , pyruvate dehydrogenase phosphatase , biochemistry , glutamate receptor , chemistry , pyruvic acid , glutamine , metabolism , gluconeogenesis , enzyme , amino acid , receptor
Pyruvate given in large doses may be neuroprotective in stroke, but it is not known to what degree the brain metabolizes pyruvate. Intravenous injection of [3‐ 13 C]pyruvate led to dose‐dependent labelling of cerebral metabolites so that at 5 min after injection of 18 mmoles [3‐ 13 C]pyruvate/kg (2 g sodium pyruvate/kg), approximately 20% of brain glutamate and GABA were labelled, as could be detected by 13 C nuclear magnetic resonance spectrometry ex vivo . Pyruvate, 9 mmoles/kg, was equivalent to glucose, 9 mmoles/kg, as a substrate for cerebral tricarboxylic acid (TCA) cycle activity. Inhibition of the glial TCA cycle with fluoroacetate did not affect formation of [4‐ 13 C]glutamate or [2‐ 13 C]GABA from [3‐ 13 C]pyruvate, but reduced formation of [4‐ 13 C]glutamine by 50%, indicating predominantly neuronal metabolism of exogenous pyruvate. Extensive formation of [3‐ 13 C]lactate from [2‐ 13 C]pyruvate demonstrated reversible carboxylation of pyruvate to malate and equilibration with fumarate, presumably in neurones, but anaplerotic formation of TCA cycle intermediates from exogenous pyruvate could not be detected. Too rapid injection of large amounts of pyruvate led to seizure activity, respiratory arrest and death. We conclude that exogenous pyruvate is an excellent energy substrate for neurones in vivo , but that care must be taken to avoid the seizure‐inducing effect of pyruvate given in large doses.