Distribution of the branched chain aminotransferase proteins in the human brain and their role in glutamate regulation

Jonathon Hull, Maya El Hindy, Patrick G. Kehoe, Katy Chalmers, Seth Love, Myra E. Conway*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

39 Citations (Scopus)

Abstract

The branched chain aminotransferase enzymes (BCAT) serve as nitrogen donors for the production of 30% of de novo glutamate synthesis in rat brain. Despite the importance of this major metabolite and excitatory neurotransmitter, the distribution of BCAT proteins in the human brain (hBCAT) remains unreported. We have studied this and report, for the first time, that the mitochondrial isoform, hBCATm is largely confined to vascular endothelial cells, whereas the cytosolic hBCATc is restricted to neurons. The majority of hBCATc-labelled neurons were either GABA-ergic or glutamatergic showing both cell body and axonal staining indicating a role for hBCATc in both glutamate production and glutamate release during excitation. Strong staining in hormone secreting cells suggests a further role for the transaminases in hormone regulation potentially similar to that proposed for insulin secretion. Expression of hBCATm in the endothelial cells of the vasculature demonstrates for the first time that glutamate could be metabolized by aminotranferases in these cells. This has important implications given that the dysregulation of glutamate metabolism, leading to glutamate excitotoxicity, is an important contributor to the pathogenesis of several neurodegenerative conditions, where the role of hBCATm in metabolizing excess glutamate may factor more prominently.

Original languageEnglish
Pages (from-to)997-1009
Number of pages13
JournalJournal of Neurochemistry
Volume123
Issue number6
DOIs
Publication statusPublished - Dec 2012

Bibliographical note

© 2012 International Society for Neurochemistry.

Keywords

  • ENDOTHELIAL-CELLS
  • GENE-EXPRESSION
  • HUMAN MITOCHONDRIAL
  • GLIAL-CELLS
  • LEUCINE
  • NEUROTRANSMITTER METABOLISM
  • IN-VIVO
  • GABAergic
  • ALZHEIMERS-DISEASE
  • glutamatergic
  • BCAT
  • endothelial glutamate regulation
  • RAT-TISSUES
  • AMINO-ACID-METABOLISM

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