Oscillations and bistability predicted by a model for a cyclical bienzymatic system involving the regulated isocitrate dehydrogenase reaction

We analyze the dynamics of a bienzymatic system consisting of isocitrate de hydrogenase (IDH, EC. 1.1.1.42), which transforms NADP(+) into NADPH, and o f diaphorase (DIA, EC 1.8.1.4), which catalyzes the reverse reaction. Exper imental evidence as well as a theoretical model showed the possibility of a coexistence between two stable steady states in this reaction system [G.M. Guidi et al. Biophys. J. 74 (1998) 1229-1240], owing to the regulatory pro perties of IDH, Here we extend this analysis by considering the behavior of the model proposed for the LDH-DIA bienzymatic system in conditions where the system is open to an influx of its substrates isocitrate and NADP(+) an d to an efflux of all metabolic species. The analysis indicates that in add ition to different modes of bistability (including mushrooms and isolas), s ustained oscillations can be observed in such conditions. These results poi nt to the isocitrate dehydrogenase reaction coupled to diaphorase as a suit able candidate for further experimental and theoretical studies of bistabil ity and oscillations in biochemical systems. The results obtained in this p articular bienzymatic system bear on other enzymatic systems possessing a c yclical nature, which are known to play significant roles in a variety of m etabolic and cellular regulatory processes. (C) 2000 Elsevier Science B.V. All rights reserved.