Design of the Oxygen and Substrate Pathways: VII. Different Structural Limits for Oxygen and Substrate Supply to Muscle Mitochondria

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Abstract
This paper integrates the results of a series of studies on the supply of O2 and substrates for oxidative muscle metabolism and draws conclusions on the role of structural design in partitioning and limiting substrate supply. The studies compared dogs and goats exercising at different intensities and combined physiological, biochemical and morphometric investigations. In both species, the rate of fatty acid oxidation reached an upper limit at low exercise intensities, and only glucose consumption was increased at higher exercise intensities. The supply of both glucose and fatty acids from the capillaries reached maximal rates at low exercise intensities; this limitation is related to the design of the sarcolemma as calculations suggest that the endothelium introduces only a small resistance to substrate flux. From these findings, it appears that the capillaries are designed to satisfy O2 supply up to maximal O2 demand. The increase in substrate supply to the mitochondria at higher exercise intensities is achieved by drawing on intracellular stores of glycogen and lipids. The size of these stores is larger in dogs than in goats, providing the athletic species with twice the fuel reserves. These findings are interpreted on the basis of a network model with fluxes partitioned between direct and indirect pathways and with some structures shared by more than one function. Whereas O2 is supplied through a direct pathway, the supply of both substrates is split temporally to allow, during exercise, immediate fuel supply to the mitochondria from intracellular stores; these are replaced from the vasculature, during periods of rest, to a size commensurate with high rates of combustion. Considering this complexity, we conclude that the results are compatible with the principle of symmorphosis applied to a network structure and that the adjustment of design to functional demand involves different structures for O2 and for substrates.