Chou T C, Talalay P
J Biol Chem. 1977 Sep 25;252(18):6438-42.
The summation of the effects of two or more reversible inhibitors of various types on the initial velocity of enzyme systems obeying Michaelis-Menten kinetics is described by the the general relation: (formula: see text) wherein v1,2,3...n is the velocity of reaction in the simultaneous presence of n inhibitors, vi is the velocity observed in the presence of each individual inhibitor, and v0 is the velocity in the absence of inhibition. The derivation is based on the assumption that each enzyme species can combine with no more than one of the inhibitors (i.e. the inhibitors are mutually exclusive). The above relationship holds irrespective of the number of inhibitors, the type of inhibition (competitive, noncompetitive, or uncompetitive), or the kinetic mechanism (sequential or ping-pong) of the enzyme reaction under consideration. Deviations from this equality define synergism or antagonism of inhibitors depending on whether the value of the left side of the above equation is greater or smaller than the right, respectively. Knowledge of the kinetic constants for substrates and inhibitors is not required. If two or more inhibitors act independently (i.e. are not mutually exclusive), their combined effects are necessarily synergistic. Under certain circumstances, described in the text, mutually nonexclusive inhibitors obey the fractional velocity product relationship: v1,2,3...n/v0 = (v1/v0) x (v2/v0) x (v3/v0)...(vn/v0).
两种或更多种不同类型的可逆抑制剂对遵循米氏动力学的酶系统初速度的影响总和，可用以下一般关系式描述：（公式：见原文）其中v1,2,3...n是n种抑制剂同时存在时的反应速度，vi是每种单独抑制剂存在时观察到的速度，v0是无抑制时的速度。该推导基于每种酶分子与不超过一种抑制剂结合的假设（即抑制剂相互排斥）。上述关系成立，与抑制剂的数量、抑制类型（竞争性、非竞争性或反竞争性）或所考虑的酶反应的动力学机制（顺序或乒乓机制）无关。根据上述等式左侧的值分别大于或小于右侧，与该等式的偏差定义了抑制剂的协同作用或拮抗作用。不需要底物和抑制剂的动力学常数知识。如果两种或更多种抑制剂独立起作用（即不相互排斥），它们的联合效应必然是协同的。在文中所述的某些情况下，相互不排斥的抑制剂遵循分数速度乘积关系：v1,2,3...n/v0 = (v1/v0) × (v2/v0) × (v3/v0)...(vn/v0) 。
