During prolonged submaximal exercise, skeletal muscle must overcome the problem of continually renewing the local supply of ATP at the ATPase site of myosin. This problem is compounded by the fact that there is little free water in the cell to enable a rapid diffusion of the compound (ATP and ADP) involved. This appears to occur via the Cr-CrP shuttle whereby the ADP produced as a result of contraction is converted to ATP via the adenylate kinase reaction with the production of AMP. The ADP used to regenerate ATP by the adenylate kinase reaction is ultimately replenished from ATP generated by the metabolic pathways and transported through the cytosol via the CK located sequentially on the myofibrils, in the cytosol, and bound to the outer surface of the inner mitochondrial membrane. The increase in the mitochondrial protein concentration of skeletal muscle that occurs with endurance training has a direct effect on improving work capacity by providing a greater potential for the CrP shuttle, produced by a greater surface area, increasing the number of transport sites for the exchange of substrates and products between the cytosol and the mitochondrial matrix, exerting a tighter control over the adenine nucleotides as they turnover during contractile and metabolic activity, and providing for a tighter control over the Embden-Meyerhof pathway to prevent excessive lactate production. The effect of these changes is to produce a more effective use of fat and carbohydrate reserves.