Power Output and Substrate Utilization in Skeletal Muscle: The Thermodynamics of Demand and Delivery Pathways

A substantial aim of this study is to show how substrate utilization depends on power output. Metabolic reactions of demand and delivery in skeletal muscle are simulated. These are the pathways of coupled adenosine triphosphate (ATP) consumption of the sarcosol (demand), and those of glucose and/or glycogen and of palmitic acid oxidation (delivery). From respective ATP formation rates, substrate utilization of respective pathways can be calculated. Results are obtained from three types of muscle fibers, which differ in their mitochondrial content. Substrate utilization is shifted from palmitic acid at low and medium power outputs towards glucose/glycogen at higher power outputs. This is caused by an increase of the conductance of the glycolytic pathway through adenosine monophosphate (AMP) activation of phosphofructokinase, while on the contrary, the conductance of the fatty acid pathway remains unchanged. The flux through this latter pathway can be markedly increased only by an increase of its conductance for membrane transport. Interferences such as uncoupling of oxidative phosphorylation, or a change from isotonic to isometric contractions must be followed by an alteration of substrate utilization, because power output and the concentration of AMP are changed concomitantly. The entire flux of both substrates through demand and delivery reactions can be formulated by one single equation. Coupling between these parts of energy metabolism is achieved by ATP cycling through ATP forming and ATP splitting reactions. A negative entropy production can occur only with coupled reactions, when the negative output affinity is gone through by a flux. But this process is more than compensated for by the positive input affinity. From this it can be concluded that the Second Law of thermodynamics, 0, always remains fulfilled, even in the presence of negative entropy production.