The hyperbolic-like decrease with time in power output during all-out exercise (AOE) correlates well with changes in “fatigue-related” metabolites: Pi, H2PO4- (Pi-) and H+. A simple mechanism of muscle fatigue during AOE, named “Pipeak-Pi-distance” mechanism, is proposed and incorporated into a dynamic computer model of the skeletal muscle bioenergetic system. It involves the dependence of the current power output (PO) on the difference between peak Pi (Pipeak), at which exercise is terminated because of fatigue in constant-power exercise (CPE), and current Pi. This mechanism can account for several dynamic properties of the skeletal muscle bioenergetic system during AOE, including PO decrease over time, (almost) identical V̇O2max in AOE and CPE, much faster on-kinetics of V̇O2 and metabolites than PO in AOE, much faster V̇O2 on-kinetics in AOE than CPE, much lower V̇O2 slow component (and higher primary phase II) at the same V̇O2max in AOE than CPE, different rates of approaching a steady-state by PO in different experiments, the V̇O2 decrease during AOE after reaching a maximum observed in some experiments and others. The mechanism is also able to explain mechanistically a broad spectrum of system behaviors, including the above-mentioned phenomena. The Pipeak-Pi-distance mechanism for AOE can be unified with the Pi-double-threshold mechanism proposed previously for CPE (and ramp-incremental exercise, RIE) into the “PiPipeak” mechanism of muscle fatigue. Generally, this unified mechanism, with Pi and Pipeak as central elements, allows to explain the similarities and differences in fatigue generation in various exercise types.

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