title: BCAA Metabolism and NH3Homeostasis.
abstract: The branched chain amino acids (BCAA) are essential amino acids required not only for growth and development, but also as nutrient signals and as nitrogen donors to neurotransmitter synthesis and glutamate/glutamine cycling. Transamination and oxidative decarboxylation of the BCAAs are catalysed by the branched-chain aminotransferase proteins (BCATm, mitochondrial and BCATc, cytosolic) and the branched-chain α-keto acid dehydrogenase enzyme complex (BCKDC), respectively. These proteins show tissue, cell compartmentation, and protein-protein interactions, which call for substrate shuttling or channelling and nitrogen transfer for oxidation to occur. Efficient regulation of these pathways is mediated through the redox environment and phosphorylation in response to dietary and hormonal stimuli. The wide distribution of these proteins allows for effective BCAA utilisation. We discuss how BCAT, BCKDC, and glutamate dehydrogenase operate in supramolecular complexes, allowing for efficient channelling of substrates. The role of BCAAs in brain metabolism is highlighted in rodent and human brain, where differential expression of BCATm indicates differences in nitrogen metabolism between species. Finally, we introduce a new role for BCAT, where a change in function is triggered by oxidation of its redox-active switch. Our understanding of how BCAA metabolism and nitrogen transfer is regulated is important as many studies now point to BCAA metabolic dysregulation in metabolic and neurodegenerative conditions.
authors.affiliation: Department of Applied Sciences, University of the West of England, Coldharbour Lane, Bristol, BS16 1QY, UK. myra.conway@uwe.ac.uk.
authors.forename: M E
authors.initials: ME
authors.lastname: Conway
authors.affiliation: Department of Human Nutrition, Foods and Exercise, Integrated Life Sciences Building (0913), 1981 Kraft Drive, Blacksburg, VA, 24060, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Hutson
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans
chemical_list: D000597:Amino Acids, Branched-Chain; D000641:Ammonia
keywords: BCAAs; BCAT; Glutamate; MSUD; Metabolon; Nitrogen shuttling; Redox-switch