The Physiological Role of the Creatine Kinase System: Evolution of Views

The development of ideas concerning the buffer and transport functions of the creatine kinase system is described. The concept of ATP compartmentation at sites of its production and utilization is critically analyzed. Kinetic, thermodynamic, and structural data used as a basis for a hypothesis on the structural and functional coupling of mitochondrial creatine kinase and adenine nucleotide translocase are comprehensively analyzed, and experimental evidence inconsistent with this hypothesis is presented. It seems that the mitochondrial creatine kinase may serve to equilibrate ADP concentration in the intermembrane space with fluctuating ADP concentrations in the cytoplasm. It is suggested that creatine kinase molecules bound to other intracellular structures (e.g., to myofibrils) may equilibrate local ADP concentrations with those present in the cytoplasm.