title: Distribution of the branched chain aminotransferase proteins in the human brain and their role in glutamate regulation.
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.
authors.affiliation: Faculty of Health and Life Sciences, University of the West of England, Bristol, UK.
authors.forename: Jonathon
authors.initials: J
authors.lastname: Hull
authors.forename: Maya El
authors.initials: ME
authors.lastname: Hindy
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Kehoe
authors.forename: Katy
authors.initials: K
authors.lastname: Chalmers
authors.forename: Seth
authors.initials: S
authors.lastname: Love
authors.forename: Myra E
authors.initials: ME
authors.lastname: Conway
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D011257:Pregnancy Proteins / Q000378:metabolism / Q000502:physiology*; D000637:Transaminases / Q000378:metabolism / Q000502:physiology*
chemical_list: D015778:Minor Histocompatibility Antigens; D011257:Pregnancy Proteins; D018698:Glutamic Acid; C490590:BCAT1 protein, human; D000637:Transaminases; C424463:BCAT2 protein, human