Newsholme P, Walsh D A
Department of Biological Chemistry, School of Medicine, University of California, Davis 95616.
Biochem J. 1992 May 1;283 ( Pt 3)(Pt 3):845-8. doi: 10.1042/bj2830845.
The regulation of phosphorylase kinase has been proposed to occur physiologically under conditions of zero-order ultrasensitivity [Meinke & Edstrom (1991) J. Biol. Chem. 266, 2259-2266]. This is also one of the conditions that recent theoretical approaches have indicated to be essential in order for an interconvertible enzyme cascade to generate a sensitive response to an effector [Cardenas & Cornish-Bowden (1989) Biochem. J. 257, 339-345]. In contrast, all published kinetic data to date have strongly suggested that activation of phosphorylase kinase by Ca2+ or phosphorylation is attributable solely to a change in affinity for phosphorylase, with no effect on the Vmax. of the reaction. In this study an attempt is made to resolve this conflict. Findings suggest that changes in Vmax. can fully account for the activation of phosphorylase kinase by the physiological mechanisms of cyclic AMP-dependent phosphorylation and increase in Ca2+ concentration.
磷酸化酶激酶的调节作用被认为在零级超敏感性条件下会发生生理性调节[Meinke和Edstrom（1991年）《生物化学杂志》266卷，2259 - 2266页]。这也是近期理论方法所指出的条件之一，即对于一个可互变的酶级联反应来说，该条件对于产生对效应物的敏感反应至关重要[Cardenas和Cornish - Bowden（1989年）《生物化学杂志》257卷，339 - 345页]。相比之下，迄今为止所有已发表的动力学数据都强烈表明，Ca²⁺或磷酸化对磷酸化酶激酶的激活仅仅归因于对磷酸化酶亲和力的变化，而对反应的最大反应速度（Vmax）没有影响。在本研究中，试图解决这一矛盾。研究结果表明，最大反应速度的变化可以完全解释通过环磷酸腺苷依赖性磷酸化的生理机制以及Ca²⁺浓度升高对磷酸化酶激酶的激活作用。
