Mendes P, Kell D B, Westerhoff H V
Department of Biological Sciences, University College of Wales, Aberystwyth.
Eur J Biochem. 1992 Feb 15;204(1):257-66. doi: 10.1111/j.1432-1033.1992.tb16632.x.
It is widely considered that a possible advantage of metabolite channelling, in which a product of an enzyme is transferred to the next enzyme in a metabolic pathway without being released to the 'bulk' solution, is that channelling can decrease the steady-state concentrations of 'pool' intermediates. This then spares the limited solvent capacity of the cell, and reduces the loss of pathway flux due to leakage or instability of the free intermediate. Recently, however, based on simulations of a particular model of a 'dynamic' channel, Cornish-Bowden ["Failure of channelling to maintain low concentrations of metabolic intermediates" (1991) Eur. J. Biochem. 195, 103-108] has argued that this is not in fact the case; his simulations indicated that the channel was rather ineffective at decreasing the concentration of the pool intermediate, and in some cases actually increased it. However, although his simulations were restricted to very specific thermodynamic and kinetic parameters, he generalised his conclusions, arguing that "channelling has no effect on the free concentration of a channelled intermediate in a pathway". By showing that, for a number of kinetic cases, the concentration of the pool intermediate did decrease substantially with increased channelling, we demonstrate here that the conclusion of Cornish-Bowden is not correct. In particular, if the reaction catalysed by the enzymes forming the channel has an equilibrium constant K higher than 1, and if the enzyme removing the product of the channel reaction is kinetically competent, channelling in the model system studied by Cornish-Bowden (1991) can decrease the steady-state concentration of the pool by a factor of 1000, independently of the mechanism of the terminal reaction and under conditions of essentially constant overall flux. If the channel is a 'static' channel, the decrease in the pool can be to arbitrarily low levels. This conclusion also holds for a system in which other reactions may consume the pool intermediate. Thus, channelling can maintain metabolite concentrations at low levels.
人们普遍认为，代谢物通道化可能具有的一个优势是，通道化能够降低“池”中间产物的稳态浓度。在代谢物通道化过程中，一种酶的产物会转移到代谢途径中的下一种酶，而不会释放到“大量”溶液中。这进而节省了细胞有限的溶剂容量，并减少了由于游离中间产物的泄漏或不稳定性导致的途径通量损失。然而，最近基于对一个“动态”通道特定模型的模拟，康沃尔-鲍登[《通道化未能维持代谢中间产物的低浓度》（1991年），《欧洲生物化学杂志》195卷，第103 - 108页]认为实际情况并非如此；他的模拟表明，该通道在降低池中间产物浓度方面相当无效，在某些情况下实际上还使其增加。然而，尽管他的模拟仅限于非常特定的热力学和动力学参数，但他却将其结论进行了推广，声称“通道化对途径中被通道化的中间产物的游离浓度没有影响”。通过表明在许多动力学情况下，随着通道化增加，池中间产物的浓度确实大幅下降，我们在此证明康沃尔-鲍登的结论是不正确的。特别是，如果构成通道的酶所催化的反应的平衡常数K大于1，并且如果去除通道反应产物的酶在动力学上是有效的，那么在康沃尔-鲍登（1991年）研究的模型系统中，通道化能够将池的稳态浓度降低1000倍，这与末端反应的机制无关，并且是在总通量基本恒定的条件下。如果通道是一个“静态”通道，池的降低可以达到任意低的水平。这一结论对于其他反应可能消耗池中间产物的系统也成立。因此，通道化能够将代谢物浓度维持在低水平。
