Craciun Gheorghe, Tang Yangzhong, Feinberg Martin
Mathematical Biosciences Institute, 231 West 18th Avenue, Ohio State University, Columbus, OH 43210, USA.
Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8697-702. doi: 10.1073/pnas.0602767103. Epub 2006 May 30.
Much attention has been paid recently to bistability and switch-like behavior that might be resident in important biochemical reaction networks. There is, in fact, a great deal of subtlety in the relationship between the structure of a reaction network and its capacity to engender bistability. In common physicochemical settings, large classes of extremely complex networks, taken with mass action kinetics, cannot give rise to bistability no matter what values the rate constants take. On the other hand, bistable behavior can be induced in those same settings by certain very simple and classical mass action mechanisms for enzyme catalysis of a single overall reaction. We present a theorem that distinguishes between those mass action networks that might support bistable behavior and those that cannot. Moreover, we indicate how switch-like behavior results from a well-studied mechanism for the action of human dihydrofolate reductase, an important anti-cancer target.
最近，人们对重要生化反应网络中可能存在的双稳性和类似开关的行为给予了极大关注。事实上，反应网络的结构与其产生双稳性的能力之间存在着大量微妙之处。在常见的物理化学环境中，一大类极其复杂的网络，采用质量作用动力学，无论速率常数取何值，都不会产生双稳性。另一方面，在相同环境中，通过某些非常简单且经典的单步总反应酶催化质量作用机制，可以诱导出双稳性行为。我们提出了一个定理，用于区分那些可能支持双稳性行为的质量作用网络和那些不能支持双稳性行为的网络。此外，我们还指出了人类二氢叶酸还原酶（一种重要的抗癌靶点）的作用机制（该机制已得到充分研究）是如何导致类似开关的行为的。
