Abstract
We do not know the mode of action of the ketogenic diet in controlling epilepsy. One
possibility is that the diet alters brain handling of glutamate, the major excitatory
neurotransmitter and a probable factor in evoking and perpetuating a convulsion. We
have found that brain metabolism of ketone bodies can furnish as much as 30% of glutamate
and glutamine carbon. Ketone body metabolism also provides acetyl-CoA to the citrate
synthetase reaction, in the process consuming oxaloacetate and thereby diminishing
the transamination of glutamate to aspartate, a pathway in which oxaloacetate is a
reactant. Relatively more glutamate then is available to the glutamate decarboxylase
reaction, which increases brain [GABA]. Ketosis also increases brain [GABA] by increasing
brain metabolism of acetate, which glia convert to glutamine. GABA-ergic neurons readily
take up the latter amino acid and use it as a precursor to GABA. Ketosis also may
be associated with altered amino acid transport at the blood–brain barrier. Specifically,
ketosis may favor the release from brain of glutamine, which transporters at the blood–brain
barrier exchange for blood leucine. Since brain glutamine is formed in astrocytes
from glutamate, the overall effect will be to favor the release of glutamate from
the nervous system.
Keywords
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Article Info
Publication History
Accepted:
July 1,
2003
Received:
June 6,
2003
Footnotes
☆Supported by Grants HD26979, NS37915 from the National Institutes of Health.
Identification
Copyright
© 2003 Elsevier Science Ltd. Published by Elsevier Inc. All rights reserved.
