Easterby J S
Department of Biochemistry, University of Liverpool, UK.
J Mol Recognit. 1993 Dec;6(4):179-85. doi: 10.1002/jmr.300060406.
When a metabolic system undergoes a transition between steady states, the lag or transition time of the system is determined by the aggregated lifetimes of the metabolite pools. This allows the transition time, and hence the temporal responsiveness of the system, to be estimated from a knowledge of the starting and finishing steady states and obviates the need for dynamic measurements. The analysis of temporal response in metabolic systems may be integrated with the general field of metabolic control analysis by the definition of a temporal control coefficient (Cei tau) in terms of flux and concentration control coefficients. The temporal control coefficient exhibits summation and other properties analogous to the flux and concentration control coefficients. For systems in which static metabolite channels exist, the major kinetic advantage of channelling is a reduction in pool sizes and, as a result, a more rapid system response reflected in a reduced transition time. The extent of the channelling advantage may therefore be assessed from a knowledge of the system transition time. This reveals that no channelling advantage is achieved at high enzyme concentrations (i.e., comparable to Km) or, in the case of 'leaky' channels, where rapid equilibrium kinetic mechanisms obtain. In the case of a perfect channel with no leakage and direct transfer of metabolite between adjacent enzyme active sites, the transition time is minimized and equal to the lifetime of the enzyme-substrate complex.
当一个代谢系统在稳态之间发生转变时，系统的滞后或转变时间由代谢物池的总寿命决定。这使得可以根据起始和结束稳态的知识来估计转变时间，进而估计系统的时间响应性，并且无需进行动态测量。通过根据通量和浓度控制系数定义时间控制系数（Cei tau），代谢系统中时间响应的分析可以与代谢控制分析的一般领域相结合。时间控制系数表现出与通量和浓度控制系数类似的求和及其他性质。对于存在静态代谢物通道的系统，通道化的主要动力学优势是减小了池的大小，结果是系统响应更快，表现为转变时间缩短。因此，可以根据系统转变时间的知识来评估通道化优势的程度。这表明在高酶浓度（即与Km相当）时，或者在“渗漏”通道且存在快速平衡动力学机制的情况下，无法实现通道化优势。对于没有渗漏且代谢物在相邻酶活性位点之间直接转移的完美通道，转变时间最小化，且等于酶 - 底物复合物的寿命。
