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Distribution of the branched chain aminotransferase proteins in the human brain and their role in glutamate regulation
Author(s) -
Hull Jonathon,
Hindy Maya El,
Kehoe Patrick G.,
Chalmers Katy,
Love Seth,
Conway Myra E.
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12044
Subject(s) - glutamate receptor , excitotoxicity , glutamatergic , biology , neurotransmitter , glutamate dehydrogenase , neurochemical , microbiology and biotechnology , biochemistry , endocrinology , central nervous system , receptor
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, hBCAT m is largely confined to vascular endothelial cells, whereas the cytosolic hBCAT c is restricted to neurons. The majority of hBCAT c‐labelled neurons were either GABA ‐ergic or glutamatergic showing both cell body and axonal staining indicating a role for hBCAT c 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 hBCAT m 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 hBCAT m in metabolizing excess glutamate may factor more prominently.