{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T03:45:58Z","timestamp":1784951158100,"version":"3.55.0"},"reference-count":85,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute","award":["R01HL161004"],"award-info":[{"award-number":["R01HL161004"]}]},{"name":"National Heart, Lung, and Blood Institute","award":["R01HL146442"],"award-info":[{"award-number":["R01HL146442"]}]},{"name":"National Heart, Lung, and Blood Institute","award":["R01HL149714"],"award-info":[{"award-number":["R01HL149714"]}]},{"name":"National Heart, Lung, and Blood Institute","award":["R01HL148151"],"award-info":[{"award-number":["R01HL148151"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymatic disorder, affects over 500 million people worldwide and is often linked to exercise intolerance due to oxidative stress, but its true impact on physical performance remains unclear. This study aimed to evaluate the physiological and metabolic effects of G6PD deficiency on endurance capacity. Using humanized mice carrying the African G6PD variant [V68M; N126D] (hG6PDA\u2212), we show that despite reduced pentose phosphate pathway activity, these mice exhibit a 10.8% increase in treadmill critical speed (CS)\u2014suggesting enhanced endurance capacity. Multi-omics profiling across red blood cells, plasma, skeletal muscle, spleen, kidney, and liver reveals metabolic adaptations, including elevated glycolysis, fatty acid oxidation, and increased mitochondrial activity, alongside heightened oxidative phosphorylation in muscle and accelerated red blood cell turnover in the spleen and liver. These findings indicate that systemic metabolic reprogramming may offset antioxidant deficiencies, potentially conferring a performance advantage. Given that G6PD deficiency affects up to 13% of African Americans and is associated with cardiovascular health disparities, our results challenge conventional exercise restrictions and highlight the need for personalized exercise guidelines for affected individuals.<\/jats:p>","DOI":"10.3390\/antiox14080927","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T12:39:29Z","timestamp":1753792769000},"page":"927","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Increased Exercise Tolerance in G6PD African Variant Mice Driven by Metabolic Adaptations and Erythrophagocytosis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8874-2150","authenticated-orcid":false,"given":"Francesca I.","family":"Cendali","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5199-8670","authenticated-orcid":false,"given":"Abby L.","family":"Grier","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6217-4063","authenticated-orcid":false,"given":"Christina","family":"Lisk","sequence":"additional","affiliation":[{"name":"Cardiovascular and Pulmonary Research Laboratory, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Dzieciatkowska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Haiman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Reisz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Harral","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Stephenson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9003-6415","authenticated-orcid":false,"given":"Ariel M.","family":"Hay","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P.","family":"Wartchow","sequence":"additional","affiliation":[{"name":"Department of Pathology, Children\u2019s Hospital Colorado, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0687-3008","authenticated-orcid":false,"given":"Paul W.","family":"Buehler","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"},{"name":"The Center for Blood Oxygen Transport, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk C.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8566-7119","authenticated-orcid":false,"given":"Travis","family":"Nemkov","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Zimring","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22903, 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