Gm. Guidi et A. Goldbeter, Oscillations and bistability predicted by a model for a cyclical bienzymatic system involving the regulated isocitrate dehydrogenase reaction, BIOPHYS CH, 83(2), 2000, pp. 153-170
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.
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