Bae W, Rittmann B E
National Institute of Environmental Research, Seoul 122-040, Republic of Korea.
Biotechnol Bioeng. 1996 Mar 20;49(6):683-9. doi: 10.1002/(SICI)1097-0290(19960320)49:6<683::AID-BIT10>3.0.CO;2-7.
A structured model of substrate-utilization kinetics that encompasses dual-limitation conditions, caused by simultaneously low concentrations of the electron donor and the electron acceptor, is developed by incorporating the internal cofactor responses into the kinetic variables. The structured model is based on an assumption that the maximum specific electron-donor-oxidation rate (q(md)) is not a constant, but is linearly controlled by the intracellular chemical potentials, log(NAD/NADH) and log(ATP/ADP . P(i)). Determination of the kinetic parameters for the dual-limitation model, using experimental data from the companion article, verifies that q(md) varies and demonstrates that the NAD/NADH ratio affects q(md) in a positive direction; thus, an increase of the ratio increases the rate of electron-donor utilization. Because the internal NAD/NADH ratio rises with an increase in S(ar) the specific electron-donor-utilization rate is accelerated by high S(a). Since the ratio also increases as the specific electron-donor-utilization rate falls, the specific rate is intrinsically accelerated by the cofactor response when it becomes low due to a depletion of electron donor. Because the cofactor responses upon changes of the external substrate concentrations are systematic, the dual-limitation model can be expressed as a function of only external concentrations of electron donor and electron acceptor, which results in a multiplicative (double-Monod) form. Thus, dual limitation by both substrates reduces the overall reaction rate below the rate expected from single limitation by only one, the most severely limiting, substrate. (c) 1996 John Wiley & Sons, Inc.
通过将内部辅因子响应纳入动力学变量，建立了一个底物利用动力学的结构化模型，该模型涵盖了由电子供体和电子受体同时低浓度引起的双重限制条件。该结构化模型基于这样一个假设：最大比电子供体氧化速率（q(md)）不是一个常数，而是由细胞内化学势log(NAD/NADH)和log(ATP/ADP·P(i))线性控制。使用来自配套文章的实验数据确定双重限制模型的动力学参数，验证了q(md)是变化的，并表明NAD/NADH比率在正向影响q(md)；因此，该比率的增加会提高电子供体的利用速率。由于内部NAD/NADH比率随着S(ar)的增加而升高，高S(a)会加速比电子供体利用速率。由于该比率也随着比电子供体利用速率的下降而增加，当由于电子供体耗尽而变得很低时，比速率会因辅因子响应而内在地加速。由于外部底物浓度变化时的辅因子响应是系统性的，双重限制模型可以仅表示为电子供体和电子受体外部浓度的函数，这导致了一种乘法（双莫诺德）形式。因此，两种底物的双重限制会使总反应速率低于仅由一种最严重限制底物的单一限制所预期的速率。(c) 1996 John Wiley & Sons, Inc.
