Investigations into the analysis and modeling of the cytochrome P450 cycle.
The main focus of our research is to explore the fundamental dynamics of the mechanism of the cytochrome P450 (CYP450) cycle. For this purpose we propose a system-theoretical approach, a time-dependent metabolic control analysis (tdMCA), to the analysis and quantitative modeling of the CYP450 catalytic pathway. This provides theoretical enlightenment for us to assess the transient response of the system to perturbations. In addition, the robustness of the cycle has also been observed, where perturbations elicit very weak responses and the system quickly recovers to the steady state (in an average of 10(-5) s). The tdMCA also shows that the two electron transfers to the cycle have different impacts on the system, and the cycle is more sensitive to the first electron than to the second one. Knowing the dynamics of transient fluctuations, the robustness of the cycle, and the effects from the key interim steps, one has a deeper understanding of the catalytic mechanism of cytochrome P450.
Wang
Yonghua
Y
Lab of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Graduate School of the Chinese Academy of Sciences, China.
Li
Yan
Y
Li
Yanhong
Y
Ma
Xiaohua
X
Yang
Shengli
S
Yang
Ling
L
D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D004548:Elasticity; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology; D008956:Models, Chemical; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D012984:Software
D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase