Branched-Chain Amino Acids: Enzyme and Substrate Regulation
Open accessAbstract
The three branched-chain amino acids (BCAAs) are the most hydrophobic of the amino acids and play crucial roles in determining the structures of globular proteins as well as the interaction of the transmembrane domains of membranous proteins with phospholipid bilayers. However, the three BCAAs do not behave identically. In terms of protein secondary structure, valine and isoleucine exhibit a definite preference for the beta-structure, whereas leucine has a higher preference for the alpha-helix. Although mutation of one BCAA to another is commonly regarded as conservative, there are well-documented examples of such substitutions that have a significant effect on protein function. The occurrence of BCAA in nature is, therefore, attributable to their primary role in protein structure, not to their secondary metabolic roles. These functions are important for almost all proteins; therefore, BCAA commonly account for approximately 20-25% of most dietary proteins. Dietary BCAA largely escape first-pass splanchnic metabolism. The first steps in their catabolism are common to all three, involving the BCAA aminotransferase (BCAT) and branched-chain alpha-keto acid dehydrogenase (BCKD). Their further metabolism employs distinct pathways to different end-products (glucose and/or ketone bodies). However, the fact that the flux-generating step for the catabolism of the three BCAAs occurs at one of the common steps indicates that the production of these downstream products are not individually regulated and, hence, may not play important individual roles. The catabolism of the BCAAs is highly regulated by both allosteric and covalent mechanisms. BCKD is inhibited by phosphorylation and activated by dephosphorylation. Allosteric inhibition of the kinase by the branched-chain keto acids (BCKA) (particularly by alpha-ketoisocaproate) serves both as a mechanism for promoting the catabolism of excess quantities of these amino acids as well as for conserving low concentrations of these dietary essential amino acids. Cytosolic and mitochondrial isoenzymes of BCAT have been identified. They are thought to play an important role in brain neurotransmitter metabolism.
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The three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine are unique among the EAAs for their roles in protein metabolism, neural function, and blood glucose and insulin regulation.
“The three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine are unique among the EAAs for their roles in protein metabolism [150], neural function [151–153], and blood glucose and insulin regulation [154].”
From International Society of Sports Nutrition Position Stand: protein and exercise (2017) · cites this paper as [154]
Citation [154] is attached to the blood-glucose and insulin-regulation clause, not the protein-metabolism or neural-function clauses. The Metabolic Disposal of the BCAAs section describes valine and isoleucine as glucogenic, but it does not establish that BCAAs regulate blood glucose or insulin. It also says their catabolism is not primarily driven by a need for glucose. No page number is supplied for this passage. (LLM, conf=0.78)
Experimental — accuracy not yet measuredBCAAs participate indirectly and directly in a variety of biochemical functions in the peripheral and central nervous systems.
“They participate indirectly and directly in a variety of biochemical functions in the peripheral and central nervous systems (Brosnan and Brosnan, 2006;Fernstrom, 2005;Sperringer et al., 2017).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Brosnan and Brosnan, 2006
The BCAAs leucine, isoleucine, and valine are a major source of cellular energy via acetyl CoA and succinyl CoA generation.
“The BCAAs leucine, isoleucine, and valine are a major source of cellular energy via acetyl CoA and succinyl CoA generation.44”
From The multifaceted contributions of mitochondria to cellular metabolism (2018) · cites this paper as [44]
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- Authors
- Brosnan, J. T., & Brosnan, M. E.
- Affiliations
- Memorial University of Newfoundland (CA)
- Corresponding author
- Brosnan, John T
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 136
- Issue
- 1
- Pages
- 207S-211S
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W1946555313
- Cited by
- 577
- References
- 39
- Citations by year
- 2026: 17 · 2025: 37 · 2024: 52 · 2023: 43 · 2022: 53 · 2021: 41 · 2020: 43 · 2019: 48 · 2018: 49 · 2017: 38 · 2016: 29 · 2015: 24 · 2014: 21 · 2013: 17 · 2012: 17
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- branched-chain amino acids, valine, isoleucine, leucine, BCAA catabolism, branched-chain ketoacid dehydrogenase, allosteric regulation, phosphorylation, alpha-ketoisocaproate, branched-chain keto acids, protein secondary structure, first-pass metabolism, ketone bodies
- MeSH terms
- Amino Acids, Branched-Chain, Transaminases, Animals, Humans, Proteins, Tissue Distribution, 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
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