title: Interactions in the Metabolism of Glutamate and the Branched-Chain Amino Acids and Ketoacids in the CNS.
abstract: Glutamatergic neurotransmission entails a tonic loss of glutamate from nerve endings into the synapse. Replacement of neuronal glutamate is essential in order to avoid depletion of the internal pool. In brain this occurs primarily via the glutamate-glutamine cycle, which invokes astrocytic synthesis of glutamine and hydrolysis of this amino acid via neuronal phosphate-dependent glutaminase. This cycle maintains constancy of internal pools, but it does not provide a mechanism for inevitable losses of glutamate N from brain. Import of glutamine or glutamate from blood does not occur to any appreciable extent. However, the branched-chain amino acids (BCAA) cross the blood-brain barrier swiftly. The brain possesses abundant branched-chain amino acid transaminase activity which replenishes brain glutamate and also generates branched-chain ketoacids. It seems probable that the branched-chain amino acids and ketoacids participate in a "glutamate-BCAA cycle" which involves shuttling of branched-chain amino acids and ketoacids between astrocytes and neurons. This mechanism not only supports the synthesis of glutamate, it also may constitute a mechanism by which high (and potentially toxic) concentrations of glutamate can be avoided by the re-amination of branched-chain ketoacids.
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. yudkoff@email.chop.edu.
authors.forename: Marc
authors.identifier: http://orcid.org/0000-0002-9628-9608
authors.initials: M
authors.lastname: Yudkoff
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007651:Keto Acids / Q000378:metabolism*
chemical_list: D000597:Amino Acids, Branched-Chain; D007651:Keto Acids; D018698:Glutamic Acid
keywords: Brain; Brain metabolism; Branched-chain amino acids; Glutamate; Metabolism