A STRUCTURED MODEL OF DUAL-LIMITATION KINETICS

A structured model of substrate-utilization kinetics that encompasses dual-limitation conditions, caused by simultaneously low concentration s of the electron donor and the electron acceptor, is developed by inc orporating the internal cofactor responses into the kinetic variables. The structured model is based on an assumption that the maximum speci fic electron-donor-oxidation rate (q(md)) is not a constant, but is li nearly controlled by the intracellular chemical potentials, log(NAD/NA DH) and log(ATP/ADP . P-i). Determination of the kinetic parameters fo r the dual-limitation model, using experimental data from the companio n article, verifies that q(md) varies and demonstrates that the NAD/NA DH ratio affects q(md) in a positive direction; thus, an increase of t he ratio increases the rate of electron-donor utilization. Because the internal NAD/NADH ratio rises with an increase in S-a, the specific e lectron-donor-utilization rate is accelerated by high S-a. Since the r atio also increases as the specific electron-donor-utilization rate fa lls, the specific rate is intrinsically accelerated by the cofactor re sponse when it becomes low due to a depletion of electron donor. Becau se the cofactor responses upon changes of the external substrate conce ntrations are systematic, the dual-limitation model can be expressed a s a function of only external concentrations of electron donor and ele ctron 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.