Abstract
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.
Highlights
Human muscles are tailored towards ATP synthesis
In the context of human endurance performance, high sustained ATP synthesis is one of the most important competitive advantages. It is increasingly recognized[1,2] that there is an evolutionary conserved trade-off between maximum-power output and maximum metabolic efficiency, which is rooted in differences in catalytic capacity of the different pathways (ATP produced per gram protein)
We find that metabolic bypass of complex I is an optimal strategy at high ATP synthesis rates
Summary
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. Metabolic models have been developed to study how limited catalytic capacity of enzymes affects ATP synthesis. 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. 1234567890():,; In the context of human endurance performance, high sustained ATP synthesis is one of the most important competitive advantages It is increasingly recognized[1,2] that there is an evolutionary conserved trade-off between maximum-power output (using fermentative pathways) and maximum metabolic efficiency (using complete oxidative phosphorylation), which is rooted in differences in catalytic capacity of the different pathways (ATP produced per gram protein). A kinetic model has been developed on the whole-body level to simulate dynamics in substrate utilization[13]
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