ATPases force generation

In summary, therefore, solution and fiber biochemistry have provided some idea about how ATP is used by actomyosin to generate force. Currently, it seems most likely that phosphate release, and also an isomerization between two AM.ADP.Pj states, are closely linked to force generation in muscle. ATP binds rapidly to actomyosin (A.M.) and is subsequently rapidly hydrolyzed by myosin/actomyosin. There is also a rapid equilibrium between M. ADP.Pj and A.M.ADP.Pj (this can also be seen in fibers from mechanical measurements at low ionic strength). The rate limiting step in the ATPase cycle is therefore likely to be release of Pj from A.M.ADP.Pj, in fibers as well as in solution, and this supports the idea that phosphate release is associated with force generation in muscle. 

The ATP in fatigued muscle is, however, well above the K , for actomyosin ATPase activity (Naiminga and Mommaerts, 1960). This indicates that the decrease in force generation is not related to a lack of ATP for crossbridge formation but... 

Quantify the correlation between changes in the state of the proposed regulatory component and parameters associated with the biological responses (force generation, shortening, ATPase activity, etc.)... 

Motors Myosins Myosin V, kinesin, dynein (IFs bind to the non-ATPase site of these motors and they act as either cargoes or supports for force generation) Kinesin, dynein... 

As discussed below in section 8.4.4.11, ATP binding provides the major push component of force, but we expect the peak in AG.p to occur at the moment of hydrolysis when the charge concentration is greatest with the momentary presence of both ADP and Pj In the synthesis function of the Fi motor of ATP synthase, we expect that the maximum repulsion occurs between the most hydrophobic side of the rotor and the ADP and Pj state and that this maximal repulsion decreases on ATP formation, which, in the consiUent view, drives ATP formation. Accordingly, because repulsion is the force that drives the ATPase function of the Fi motor and because repulsion drives rotation, ATP binding would provide near-maximal force generation, enhanced only at the moment of hydrolysis to form ADP plus Pj. 

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