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Cited by 76Muscle metabolism and nutritionCardiovascular and exercise physiologyAmino Acid Enzymes and Metabolism

Disruption of bcaa metabolism in mice impairs exercise metabolism and endurance

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She, Pengxiang, Zhou, Yingsheng, Zhang, Zhiyou, Griffin, Kathleen, Gowda, Kavitha, Lynch, Christopher J.·2010·Journal of Applied Physiology
DOI 10.1152/japplphysiol.01248.2009PMC PMC2853195
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Abstract

Exercise enhances branched-chain amino acid (BCAA) catabolism, and BCAA supplementation influences exercise metabolism. However, it remains controversial whether BCAA supplementation improves exercise endurance, and unknown whether the exercise endurance effect of BCAA supplementation requires catabolism of these amino acids. Therefore, we examined exercise capacity and intermediary metabolism in skeletal muscle of knockout (KO) mice of mitochondrial branched-chain aminotransferase (BCATm), which catalyzes the first step of BCAA catabolism. We found that BCATm KO mice were exercise intolerant with markedly decreased endurance to exhaustion. Their plasma lactate and lactate-to-pyruvate ratio in skeletal muscle during exercise and lactate release from hindlimb perfused with high concentrations of insulin and glucose were significantly higher in KO than wild-type (WT) mice. Plasma and muscle ammonia concentrations were also markedly higher in KO than WT mice during a brief bout of exercise. BCATm KO mice exhibited 43-79% declines in the muscle concentration of alanine, glutamine, aspartate, and glutamate at rest and during exercise. In response to exercise, the increments in muscle malate and alpha-ketoglutarate were greater in KO than WT mice. While muscle ATP concentration tended to be lower, muscle IMP concentration was sevenfold higher in KO compared with WT mice after a brief bout of exercise, suggesting elevated ammonia in KO is derived from the purine nucleotide cycle. These data suggest that disruption of BCAA transamination causes impaired malate/aspartate shuttle, thereby resulting in decreased alanine and glutamine formation, as well as increases in lactate-to-pyruvate ratio and ammonia in skeletal muscle. Thus BCAA metabolism may regulate exercise capacity in mice.

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  • The disruption of BCAA metabolism was shown to severely impair endurance exercise to exhaustion within the skeletal muscle of rodents.

    “The disruption of BCAA metabolism was shown to severely impair endurance exercise to exhaustion within the skeletal muscle of rodents [176].”

    From Regulation of Energy Substrate Metabolism in Endurance Exercise (2021) · cites this paper as [176]

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Authors
She, P., Zhou, Y., Zhang, Z., Griffin, K., Gowda, K., & Lynch, C. J.
Affiliations
  • Departments of 1Cellular and Molecular Physiology and
  • Beijing Hospital (CN)
  • Pennsylvania State University (US)
Corresponding author
She, Pengxiang
ORCID
Venue
Journal of Applied Physiology
Publisher
American Physiological Society
Published
2010-04
Volume
108
Issue
4
Pages
941-949
ISSN
  • 0161-7567 (ISSN-L)
  • 8750-7587
  • 1522-1601
DOI
10.1152/japplphysiol.01248.2009
PMC
PMC2853195
OpenAlex
W2162279856
Cited by
75
References
52
Citations by year
2026: 1 · 2025: 6 · 2024: 3 · 2023: 6 · 2022: 3 · 2021: 7 · 2020: 9 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 9 · 2015: 8 · 2014: 3 · 2013: 3
FWCI
1.26
Type
journal article
Language
en
Open access
Locations
  • Journal of Applied Physiology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Vanderbilt University
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-062880, R01DK053843, R01DK062880)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
branched-chain amino acids, BCAA catabolism, exercise endurance, skeletal muscle metabolism, lactate/pyruvate ratio, ammonia, malate-aspartate shuttle, purine nucleotide cycle, exercise intolerance, BCAA supplementation
MeSH terms
Amino Acids, Branched-Chain, Transaminases, Ammonia, Animals, Aspartic Acid, Blood Glucose, Exercise Test, Physical Exertion, Glucose, Insulin, Ketoglutaric Acids, Male, Maleates, Mice, Inbred C57BL, Physical Conditioning, Animal, Exercise Tolerance, Mice, Knockout, Muscle, Skeletal, Lactic Acid, Mice

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