Cytochrome P-450 spin state: Inorganic biochemistry of haem iron ligation and functional significance

Abstract

Haem ligation in cytochrome P-450 has been reviewed and the nature of the fifth and sixth ligands of the haemoprotein in the ferric low-spin, ferric high-spin, ferrous and ferrous-carbon-monoxy states have been discussed. Factors controlling the cytochrome P-450 spin equilibrium have been described, including substrate and functional components of the mixed-function oxidase system. In addition, a thermodynamic model describing the interaction of substrate with ferric cytochrome P-450 has been developed in terms of the micro-equilibrium constants governing substrate binding. The functional significance of the cytochrome P-450 spin state with particular reference to control of the first electron reduction of the haemoprotein has been summarized, and a subsequent validation of the spin-redox coupling model of cytochrome P-450-dependent catalysis has been presented.