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Nilsson A, Björnson E, Flockhart M, Larsen FJ, Nielsen J
Nat Commun 10 (1) 5072 [2019-11-07; online 2019-11-07]
Human muscles are tailored towards ATP synthesis. When exercising at high work rates muscles convert glucose to lactate, which is less nutrient efficient than respiration. There is hence a trade-off between endurance and power. Metabolic models have been developed to study how limited catalytic capacity of enzymes affects ATP synthesis. Here we integrate an enzyme-constrained metabolic model with proteomics data from muscle fibers. We find that ATP synthesis is constrained by several enzymes. A metabolic bypass of mitochondrial complex I is found to increase the ATP synthesis rate per gram of protein compared to full respiration. To test if this metabolic mode occurs in vivo, we conduct a high resolved incremental exercise tests for five subjects. Their gas exchange at different work rates is accurately reproduced by a whole-body metabolic model incorporating complex I bypass. The study therefore shows how proteome allocation influences metabolism during high intensity exercise.
PubMed 31699973
DOI 10.1038/s41467-019-12934-8
Crossref 10.1038/s41467-019-12934-8
pmc: PMC6838197
pii: 10.1038/s41467-019-12934-8