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New insights into the role of the branched-chain aminotransferase proteins in the human brain

Hull, Jonathon; Patel, Vinood B.; Hutson, Susan M.; Conway, Myra E.


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Jonathon Hull
Senior Lecturer in Biomedical Sci (Biochemistry)

Vinood B. Patel

Susan M. Hutson

Myra Conway
Occasional Associate Lecturer - CHSS - DAS


© 2015 Wiley Periodicals, Inc. The human cytosolic branched-chain aminotransferase (hBCATc) enzyme is strategically located in glutamatergic neurons, where it is thought to provide approximately 30% of de novo nitrogen for brain glutamate synthesis. In health, glutamate plays a dominant role in facilitating learning and memory. However, in patients with Alzheimer's disease (AD), synaptic levels of glutamate become toxic, resulting in a direct increase in postsynaptic neuronal calcium, causing a cascade of events that contributes to the destruction of neuronal integrity and cell death, pathological features of AD. Our group is the first to map the hBCAT proteins to the human brain, where cell-specific compartmentation indicates key roles for these proteins in regulating glutamate homeostasis. Moreover, increased expression of hBCAT was observed in the brains of patients with AD relative to matched controls. We reflect on the importance of the redox-active CXXC motif, which confers novel roles for the hBCAT proteins, particularly with respect to substrate channeling and protein folding. This implies that, in addition to their role in glutamate metabolism, these proteins have additional functional roles that might impact redox cell signaling. This review discusses how these proteins behave as potential neuroprotectors during periods of oxidative stress. These findings are particularly important because an increase in misfolded proteins, linked to increased oxidative stress, occurs in several neurodegenerative conditions. Together, these studies give an overview of the diverse role that these proteins play in brain metabolism, in which a dysregulation of their expression may contribute to neurodegenerative conditions such as AD.


Hull, J., Patel, V. B., Hutson, S. M., & Conway, M. E. (2015). New insights into the role of the branched-chain aminotransferase proteins in the human brain. Journal of Neuroscience Research, 93(7), 987-998.

Journal Article Type Review
Acceptance Date Dec 21, 2014
Publication Date Jul 1, 2015
Journal Journal of Neuroscience Research
Print ISSN 0360-4012
Electronic ISSN 1097-4547
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 93
Issue 7
Pages 987-998
Keywords hBCAT, glutamate, neuronal toxicity, redox, protein folding, neurodegeneration
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