Interactions of mitochondrial ATP synthesis and the creatine kinase equilibrium in skeletal muscle

In skeletal muscle, creatine kinase imposes constraints on the concentrations of phosphocreatine, creatine, ATP and ADP, which complicate our understanding of the regulation of mitochondrial ATP synthesis, because correlations between oxidation rate (Q) and metabolite concentrations cannot prove causal relations. Two kinds of theory of mitochondrial control in vivo have evolved, based on (i) the hyperbolic relationship between Q and cytosolic [ADP] and (ii) linear correlations between Q and, for example, free energy of ATP hydrolysis. This paper examines some relationships between these theories in order to show (i) to what extent they may be regarded as different expressions of the same metabolic mechanisms, (ii) how they can be understood in terms of general principles of feedback control, and (iii) how they explain relationships between mitochondrial function and resting metabolite concentrations.