The modeling of the actomyosin subfragment-1 ATPase activity.

In summary the four state model can at least qualitatively account for all of the available steady state and presteady state data. In order to account for the ATPase data, the four state model predicts a linear plot at low actin concentrations that extrapolates to a considerably higher Vmax and a weaker Kapp than measured experimentally. The inhibition term then dominates wrapping the predicted curve around the data. However, the four state model can account for the ATPase data within an acceptable margin of error. Controversy exists over how well the four state model can account for the burst magnitude. Stein et al., working under conditions where a four- to eightfold difference exists between KATPase and Kbinding, found that the four state model was inadequate for accounting for their quench flow burst data. On the other hand, Rosenfeld and Taylor, working under conditions where the ratio of Kbinding to KATPase was of the order of three, found a somewhat better fit to the quench flow burst data. Both laboratories, however, found that the fluorescence burst appeared larger than could be explained by the four state model. Of interest, Stein et al. found that their burst measurements were somewhat smaller than those predicted by the six state model. However, unlike the ATPase activity, the magnitude measurements are quite difficult, and therefore the results must be viewed as less conclusive. Finally, the four state model can qualitatively account for the rise in the fluorescence rate as a function of the actin concentration, but has difficulty accounting for it quantitatively. However, because of turbidity transients that may be occurring during the measurement, these data are also not as conclusive as they might be. On the other hand the six state model clearly fits the data better, but this is not surprising considering the increased degrees of freedom afforded this model. Controversy continues concerning the interpretation of the kinetics of the crosslinked actoS-1, especially the kinetics of the 18O exchange that appears on the surface to support a four state model in the case of skeletal S-1, but to oppose a four state model in the case of cardiac S-1. Further work will be necessary to determine the adequacy of the models discussed.