Nonlinear dynamics of the peroxidase-oxidase reaction. II. Compatibility of an extended model with previously reported model-data correspondences

In the course of formulating detailed models of complex chemical reactions, it is sometimes the case that modifications intended to account for one se t of experimental observations wind up destroying a model's ability to acco unt for other results. Here, we consider a recently proposed model of the p eroxidase-oxidase reaction which derives from an earlier scheme via the add ition of NADH oxidation by superoxide anion or its protonated form, hydrope roxyl radical. This modification was introduced to account for the observat ion of bistability and bursting at enzyme concentrations less than 0.5 muM Left unanswered in our previous paper was the matter of whether the propose d "fix" invalidates previously published examples of model-data agreement a t higher enzyme concentrations. In the present paper, we show that under th ese latter circumstances, the new mechanism is as good as, and in some inst ances superior to, its predecessor. More generally, we argue that the conse quences of NADH oxidation by O-2(-) or HO2. should be manifest principally at low enzyme concentrations, thereby offering a "global" explanation of ou r findings, Neither our original model, nor the derivative scheme treated h ere, provides for reactions involving NAD dimers, a species in which there has recently been renewed interest. Most importantly, it has been proposed to replace the reduction of coIII (an enzyme intermediate) by NAD radicals, a reaction for which there is no direct evidence, with the corresponding r eaction involving NAD(2). While a detailed assessment of the consequences o f dimer chemistry to theoretical peroxidase-oxidase dynamics is beyond the scope of the present investigation, it is easily documented that this subst itution, by itself, abolishes oscillatory behavior for all model parametriz ations previously considered. Moreover, this result appears to obtain for a rbitrarily small values of the associated rate constant. Whether or not the inclusion of additional dimer reactions can restore the model's ability to account for experimental observations of complex dynamics remains to be de termined.