Guide to Cytochromes P450

Part 1 Introduction: historical background; isolation, purification and characterization; spectral and related physiochemical properties; substrate-binding spectra; polarized optical spectroscopy; vibrational spectroscopy; magnetic resonance spectroscopy; Mossbauer spectroscopy; EXAFS spectroscopy; other physical methods; x-ray crystallography; redox potentials and their equilibria; other physiochemical and structural studies. Part 2 Evolution of the P450 superfamily: the P450 phylogenetic tree; evolutionary aspects of P450 function; conclusion; P450 nomenclature. Part 3 The P450 catalytic cycle: the P450 catalytic cycle; nature of the oxygenating species; participation of active site amino acids in P450 oxygenations; thermodynamics of P450 substrate binding and spin state equilibrium; the coupling of redox and spin equilibria; redox potential and redox interactions in the P450 system; interactions between redox components; protein-lipid interactions in the P450 system; a proposed mechanistic scheme for the P450 catalytic cycle. Part 4 P450 substrate specificity and metabolism: endogenous metabolism; exogenous metabolism; the CYP1 family; the CYP2 family; the CYP3 family; exogenous metabolism by other CYP enzymes. Part 5 Induction, regulation and inhibition: induction and regulation of P450 genes; regulatory elements in P450 genes; the toxic consequences of induction; heterologous expression systems and in vitro models; inhibition of cytochrome P450; competitive inhibitors; irreversible and mechanism-based inhibitors; therapeutic and agrochemical uses of P450 inhibitors; metal ions as P450 inhibitors. Part 6 Structural models of P450s and related topics: P450 modelling; physical methods; P450 sequence alignment; general features of P450 crystal structures and sequences; recommended procedure for homology modelling of P450s; eukaryotic P450s modelled from P450 BM3 (CYP 102); evaluation of P450-mediated toxicity by the COMPACT approach; conclusions and future prospects.