Stein L A
Department of Medicine, Health Sciences Center, State University of New York, Stony Brook 11794-8171.
Cell Biophys. 1988 Jan-Jun;12:29-58. doi: 10.1007/BF02918349.
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.
总之，四态模型至少在定性上能够解释所有现有的稳态和前稳态数据。为了解释ATP酶数据，四态模型预测在低肌动蛋白浓度下呈线性图，外推至比实验测量值高得多的Vmax和较弱的Kapp。然后抑制项占主导，使预测曲线围绕数据。然而，四态模型可以在可接受的误差范围内解释ATP酶数据。关于四态模型对爆发幅度的解释程度存在争议。斯坦因等人在KATP酶和K结合之间存在四到八倍差异的条件下工作，发现四态模型不足以解释他们的猝灭流动爆发数据。另一方面，罗森菲尔德和泰勒在K结合与KATP酶的比率约为三的条件下工作，发现与猝灭流动爆发数据的拟合度稍好一些。然而，两个实验室都发现荧光爆发似乎比四态模型所能解释的要大。有趣的是，斯坦因等人发现他们的爆发测量值比六态模型预测的值略小。然而，与ATP酶活性不同，幅度测量相当困难，因此结果必须被视为不太具有决定性。最后，四态模型可以定性地解释荧光速率随肌动蛋白浓度的增加，但在定量解释方面存在困难。然而，由于测量过程中可能出现的浊度瞬变，这些数据也不像可能的那样具有决定性。另一方面，六态模型显然与数据拟合得更好，但考虑到该模型具有更多的自由度，这并不奇怪。关于交联肌动蛋白S-1动力学的解释，特别是18O交换的动力学，仍然存在争议，在骨骼肌S-1的情况下，表面上的18O交换似乎支持四态模型，而在心肌S-1的情况下则反对四态模型。需要进一步的工作来确定所讨论模型的适用性。
