During muscular work, chemical energy is converted into mechanical energy. The site of this energy exchange, which involves the biological energy currency ATP, is the cross-bridges between the contractile proteins actin and myosin, and the energy is used during the breaking and reattachment cycles of the cross-bridges. The terminal phosphate group and ADP moiety of ATP are transferred to the participating systems in the contractile system, and eventually Pi and ADP are released so that, when the net reaction is completed, ATP has been hydrolysed. The resynthesis of ATP from ADP and Pi occurs from some of the energy made available in the oxidative reactions of the cell. Consequently, the energy conserved during oxidation is transferred to the processes that utilize energy (e.g. muscular contraction) via the ATP/ADP-coupled system in Scheme 1. It cannot be emphasized too strongly that ATP is not stored in the cell; its concentration in muscle is only 5-7m~ (see Beis & Newsholme, 1975), which would be depleted in less than a second during contraction unless it is resynthesized. Furthermore, to maintain the steady-state concentration of ATP, the increase in the rate of resynthesis must equal precisely that of utilization (see Newsholme & Start, 1973). That this occurs is demonstrated by the many observations that the ATP concentration remains remarkably constant despite very large variations in the power output of a given muscle. These observations strongly suggest the existence of specific mechanisms that regulate the rate of ATP formation to that of its utilization. These mechanisms must be sensitive, precise and permit the rapid transfer of information between the utilizing and
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Newsholme et al. (1978) studied this question.