Design of exogenous fuel supply systems: adaptive strategies for endurance locomotion

The prolonged performance of submaximal exercise depends on the adequate supply of exogenous fuels (e.g., hepatic glucose) to slow down the use of endogenous substrates (e.g, intramuscular fat or glycogen) and delay their depletion. This paper investigates the adaptive strategies available to vertebrates for increasing the rate of exogenous fuel supply in endurance locomotion. Two steps can be defined for the design of a "good" system: (i) the choice of oxidizable fuels and storage sites that maximize the rate of energy transfer to the working muscle and (ii) the provision of adequate regulatory mechanisms which alter substrate fluxes rapidly in response to work of different intensities. The principal oxidizable fuels used by vertebrates (free fatty acids (FFA), glucose, and lactate) are examined to determine the major constraints on maximal supply rates. The delivery of albumin binding sites to adipose tissue represents a specific constraint on FFA transport to working muscles. Furthermore, because the supply of all exogenous fuels is probably limited by membrane transport, animals requiring the rapid use of oxidizable substrates to sustain locomotion can follow two strategies: (i) switch to endogenous substrates whenever possible to avoid this constraint and (ii) evolve different transmembrane fuel carriers or augment the density of existing ones to increase maximal rates of substrate translocation across cell membranes.