Hardie D G, Salt I P, Hawley S A, Davies S P
Biochemistry Department, Dundee University, MSI/WTB Complex, Dow Street, Dundee DD1 5EH, Scotland, UK.
Biochem J. 1999 Mar 15;338 ( Pt 3)(Pt 3):717-22.
The AMP-activated protein kinase cascade is activated by elevation of AMP and depression of ATP when cellular energy charge is compromised, leading to inhibition of anabolic pathways and activation of catabolic pathways. Here we show that the system responds in intact cells in an ultrasensitive manner over a critical range of nucleotide concentrations, in that only a 6-fold increase in activating nucleotide is required in order for the maximal activity of the kinase to progress from 10% to 90%, equivalent to a co-operative system with a Hill coefficient (h) of 2.5. Modelling suggests that this sensitivity arises from two features of the system: (i) AMP acts at multiple steps in the cascade (multistep sensitivity); and (ii) the upstream kinase is initially saturated with the downstream kinase (zero-order ultrasensitivity).
当细胞能量状态受损时，AMP激活的蛋白激酶级联反应会因AMP升高和ATP降低而被激活，从而导致合成代谢途径受到抑制，分解代谢途径被激活。在此，我们表明该系统在完整细胞中，在关键的核苷酸浓度范围内以超敏感的方式做出反应，即仅需激活核苷酸增加6倍，激酶的最大活性就能从10%提升至90%，这相当于一个希尔系数（h）为2.5的协同系统。模型表明，这种敏感性源于该系统的两个特征：（i）AMP在级联反应的多个步骤起作用（多步敏感性）；以及（ii）上游激酶最初被下游激酶饱和（零级超敏感性）。
