FROM BISTABILITY TO OSCILLATIONS IN A MODEL FOR THE ISOCITRATE DEHYDROGENASE REACTION

Considered is a bienzymatic system consisting of isocitrate dehydrogen ase (IDH, EC 1.1.1.42), which transforms NADP(+) into NADPH, and of di aphorase (DIA, EC 1.8.1.4), which catalyzes the reverse reaction. Expe rimental evidence as well as a theoretical model show the possibility of a coexistence between two stable steady stales in this reaction sys tem. The phenomenon originates from the regulatory properties of IDH. We extend the analysis of a theoretical model proposed for the IDH-DIA bienzymatic system and investigate the occurrence of different modes of bistability, with or without hysteresis, i.e. in the presence of tw o or only one limit point bounding the domain of multiple steady state s. The analysis indicates that the two types of bistability may someti mes be observed sequentially as a given control parameter is progressi vely increased. We further obtain conditions in which sustained oscill ations develop in the model. These results establish the isocitrate de hydrogenase reaction coupled to diaphorase as a suitable candidate for further experimental and theoretical studies of bistability and oscil lations in biochemical systems. (C) 1998 Elsevier Science B.V. All rig hts reserved.