The cytosolic and mitochondrial branched-chain aminotransferase

Conway, Myra E.; Hutson, Susan

Abstract

Key Points
• The branched chain aminotransferases (BCAT) are PLP dependent proteins which catalyze the transfer of an amino group from the donor amino acid to α-ketoglutarate, forming glutamate and the respective keto acids.
• Structurally the BCAT proteins are homodimers, where the active site between each isoform is largely conserved.
• The cytosolic and mitochondrial isoforms show cell and tissue specific expression where the aminotransferase proteins play an integrated role in shuttling metabolites between cells and tissues.
• These anaplerotic shuttles interface with core metabolic pathways and protein complexes such as the branched-chain α-keto acid dehydrogenase complex and glutamate dehydrogenase, respectively, indicating a role in the regeneration of key metabolites such as the primary neurotransmitter glutamate.
• Leucine is a nutrient signal and involved in mTOR signalling, which controls the synthesis of cellular protein levels.
• Moreover, the BCAT proteins have a unique redox active CXXC motif regulated through changes in the redox environment, likely to play a key role in this signalling mechanism.
• Site-directed mutagenesis studies have identified that the N-terminal cysteine acts as the ‘redox sensor’ and the C-terminal cysteine as its resolving partner, which permits reversible regulation.
• Oxidation, S-nitrosation and S-glutathionylation are important redox regulators of BCAT activity and are reversibly controlled through the glutaredoxin/glutathione system.
• Biochemical and X-ray crystallography studies of the redox-active mutant proteins describe the importance of the N-terminal cysteine in the orientation of the substrate and its interaction with key residues of the interdomain loop.

• Publication Date: Oct 15, 2015
• Peer Reviewed: Peer Reviewed
• Volume: 1
• Pages: 25-40
• Series Title: Nutrition and Health
• Book Title: Branched Chain Amino Acids in Clinical Nutrition
• ISBN: 9781493919222
• DOI: https://doi.org/10.1007/978-1-4939-1923-9_3
• Keywords: BCATm, BCATc, brain-glutamate metabolism, metabolite shuttling, BCKDC, redox-regulation, S-nitrosylation and X-ray crystallography
• Public URL: https://uwe-repository.worktribe.com/output/804570
• Publisher URL: http://dx.doi.org/10.1007/978-1-4939-1923-9_3
• Contract Date: Sep 11, 2014