The effects of ketone bodies on brain metabolism of glutamate and GABA were studied in three different systems: synaptosomes, cultured astrocytes and the whole animal. In synaptosomes the addition of either acetoacetate or 3-OH-butyrate was associated with diminished consumption of glutamate via transamination to aspartate and increased formation of labelled GABA from either L-[2H5-2,3,3,4,4]glutamine or L-[15N]glutamine. There was no effect of ketone bodies on synaptosomal GABA transamination. An increase of total forebrain GABA and a diminution of aspartate was noted when mice were injected intraperitoneally with 3-OH-butyrate. In cultured astrocytes the addition of acetoacetate to the medium was associated with a significantly enhanced rate of citrate production and with a diminution in the rate of conversion of [15N]glutamate to [15N]aspartate. These data are consistent with the hypothesis that the metabolism of ketone bodies to acetyl-CoA results in a diminution of the pool of brain oxaloacetate, which is consumed in the citrate synthetase reaction (oxaloacetate + acetyl-CoA → citrate). As less oxaloacetate is available to the aspartate aminotransferase reaction, thereby lowering the rate of glutamate transamination, more glutamate becomes accessible to the glutamate decarboxylase pathway, thereby favoring the synthesis of GABA.
Marc Yudkoff, MD
Children’s Hospital of Philadelphia
1 Children’s Center, Abramson Building
Philadelphia, PA 19104-4318 (USA)
Tel. +1 215 590 3412, Fax +1 215 590 3779, E-Mail firstname.lastname@example.org
Received: Received: January 5, 1998
Accepted: February 13, 1998
Number of Print Pages : 7
Number of Figures : 4, Number of Tables : 2, Number of References : 64
Vol. 20, No. 4-5, Year 1998 (Cover Date: July-October 1998)
Journal Editor: A.T. Campagnoni, Los Angeles, Calif.
ISSN: 0378–5866 (print), 1421–9859 (Online)
For additional information: http://www.karger.com/journals/dne
Article / Publication Details
Published online: 10/30/1998
Issue release date: July–October 1998
Number of Print Pages: 7
Number of Figures: 4
Number of Tables: 2
ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)
For additional information: http://www.karger.com/DNE
Copyright / Drug Dosage
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