Juska A, de Foresta B
Institute of Biochemistry, Vilnius, Lithania.
Biochim Biophys Acta. 1995 Jun 14;1236(2):289-98. doi: 10.1016/0005-2736(95)00062-8.
A mathematical model relating the activity of adenylate cyclase (AC) with concentrations of stimulators, equilibrium dissociation constants, specific activity and efficacies of AC depending on the states of its binding sites has been developed and used for analysis of the data on activation of AC of bovine adrenal cortex plasma membranes presented in (De Foresta et al. (1987) FEBS Lett. 216, 107-112). Equilibrium dissociation constants. chi h and chi l, corresponding to high- and low-affinity forskolin-binding sites were estimated to be 0.37 and 17 microM: these constants characterize forskolin's potency more adequately than does ED50, the concentration eliciting half-asymptotic activity of AC. Corticotropin does not affect the affinity of AC for forskolin whereas fluoride increases this affinity, thus augmenting forskolin's potency. Hormone receptor of adenylate cyclase of bovine adrenal cortex has been suggested to have two or more binding sites for corticotropin. Some unidentified factor(s) may be responsible for the differences found in adenylate cyclase activity in different experiments carried out under similar conditions. The model applied for the analysis may be thought to be the best means for the moment to relate dose-response dependencies with what is known or can be hypothesized about the mechanisms underlying activation of adenylate cyclase.
已建立一个数学模型，该模型将腺苷酸环化酶（AC）的活性与刺激剂浓度、平衡解离常数、AC的比活性以及取决于其结合位点状态的效能相关联，并用于分析（De Foresta等人，（1987年）《欧洲生物化学学会联合会快报》216，107 - 112）中所呈现的牛肾上腺皮质质膜AC激活的数据。对应于高亲和力和低亲和力福斯高林结合位点的平衡解离常数χh和χl估计分别为0.37和17μM：这些常数比引起AC半渐近活性的浓度ED50更充分地表征了福斯高林的效力。促肾上腺皮质激素不影响AC对福斯高林的亲和力，而氟化物增加这种亲和力，从而增强福斯高林的效力。已提出牛肾上腺皮质腺苷酸环化酶的激素受体对促肾上腺皮质激素有两个或更多个结合位点。在相似条件下进行的不同实验中发现的腺苷酸环化酶活性差异可能由一些未确定的因素导致。用于分析的该模型可能被认为是目前将剂量 - 反应依赖性与已知的或可假设的腺苷酸环化酶激活潜在机制相关联的最佳方法。
