Branched-chain amino acids in skeletal and cardiac muscles: a review of metabolic variations and cancer’s impact
Year: 2026
Type: review
Abstract: Branched-chain amino acids (BCAA) - leucine, isoleucine, and valine - serve as essential regulators of energy homeostasis, protein turnover, and nutrient signaling in striated muscle. However, their metabolic processing varies substantially across tissues. This review contrasts BCAA metabolism in skeletal versus cardiac muscle and evaluates how cancer alters it. Skeletal muscle functions as the main site for whole-body BCAA transamination and oxidation, distributing these amino acids between protein synthesis and oxidative catabolism in line with physiological needs. In comparison, the myocardium maintains low baseline BCAA oxidation, depends primarily on fatty acids and glucose, and tightly limits BCAA catabolic flux to prevent the buildup of intermediates that would undermine mitochondrial function. In malignancies, BCAA metabolism is reconfigured in a way that depends on tumor type: many tumors increase BCAA uptake and suppress catabolism in order to preserve intracellular stores, as a result maintaining mechanistic target of rapamycin complex 1 (mTORC1) signaling and supporting proliferation. Using lung, pancreatic and colorectal cancers as main examples, we outline how this tumor-driven metabolic rewiring is linked to cancer cachexia - a multi-organ syndrome in which inflammation, mitochondrial dysfunction, and impaired anabolic signaling promote muscle and cardiac wasting rather than simple substrate limitation. We describe first the mechanisms shared by skeletal and cardiac muscle, then the features specific to each tumor type, and we distinguish throughout between cardiac evidence obtained in tumor-bearing hosts and inferences extrapolated from heart failure. We conclude that interventions directed at BCAA are most reasonable early in the disease course, and only when paired with approaches that suppress inflammation and restore mitochondrial quality control. We also identify priorities for tissue-specific biomarkers and for future research.
Source: Frontiers in Physiology
Institution: Medical University of Warsaw
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223182959