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Amino acid homeostasis links essential and nonessential amino acid supply with branched\u2010chain amino acid (BCAA) catabolism, one\u2010carbon metabolism, mechanistic target of rapamycin complex 1 (mTORC1)\/general control nonderepressible 2 (GCN2) nutrient sensing, glutathione\u2010dependent redox control, epigenetic regulation, and the gut microbiota\u2013amino acid axis. When this network is disturbed, amino acid flux can contribute to disease initiation and progression rather than simply mirroring established pathology. This review synthesizes how amino acid metabolism supports the nervous, cardiovascular, digestive, metabolic\u2013endocrine, immune, skeletal, urinary and reproductive systems, as well as malignant and inherited metabolic disorders. We also examine how pathway\u2010level disturbances converge on excitotoxicity, endothelial dysfunction, insulin resistance, inflammation, fibrosis, immune escape, toxic metabolite accumulation, and impaired fertility. Rather than catalog isolated findings, we emphasize unifying principles and unresolved controversies, including the context\u2010dependent effects of BCAA signaling, the causal versus biomarker status of circulating amino acid signatures, host\u2013gut microbiome crosstalk, and the therapeutic window of dietary, enzymatic, transporter\u2010targeted, and microbiota\u2010based interventions. Finally, we assess clinical translation, drawing lessons from late\u2010stage trial failures and emerging strategies with realistic potential for precision metabolic therapy.<\/jats:p>","DOI":"10.1002\/mco2.70930","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T07:06:53Z","timestamp":1787900813000},"source":"Crossref","is-referenced-by-count":0,"title":["Amino Acid Metabolism in Health and Disease"],"prefix":"10.1002","volume":"7","author":[{"given":"Zhiwei","family":"Su","sequence":"first","affiliation":[{"name":"Department II of Digestive Diseases, Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Interdisciplinary Integrative 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