Noise-Induced Breakdown of the Michaelis-Menten Equation in Steady-State Conditions

Noise-Induced Breakdown of the Michaelis-Menten Equation in Steady-State Conditions
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DOI:
10.1103/physrevlett.102.218103
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发表时间:
2009-05-29
影响因子:
8.6
通讯作者:
Grima, R.
Grima, R.
中科院分区:
物理与天体物理1区
文献类型:
--
作者:
Grima, R.

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Michaelis-Menten(MM)方程是酶动力学的基本方程,也是许多生物系统模型的基本构件。我们在一个小的亚细胞隔间内建立了一个酶动力学的随机微观模型。通过理论和模拟,我们证明了即使在稳态代谢条件下,本征噪声也会导致MM方程的崩溃。特别地,我们证明了(I)给定反应速度,确定性的速率方程可以严重低估稳态细胞内底物浓度;(Ii)不同的反应方案在宏观水平上是不可区分的,因为它们在亚细胞空间中由相同的MM方程描述,遵循明显不同的方程。
The Michaelis-Menten (MM) equation is the basic equation of enzyme kinetics; it is also a basic building block of many models of biological systems. We build a stochastic and microscopic model of enzyme kinetics inside a small subcellular compartment. Using both theory and simulations, we show that intrinsic noise induces a breakdown of the MM equation even if steady-state metabolic conditions are enforced. In particular, we show that (i) given a reaction velocity, deterministic rate equations can severely underestimate steady-state intracellular substrate concentrations and (ii) different reaction schemes which on a macroscopic level are indistinguishable because they are described by the same MM equation obey distinctly different equations in subcellular compartments.