Introduction

The story of how cytochrome P450 was first discovered begins about 40 years ago with the work of Axelrod (1955) and Brodie et al. (1955) who reported that an enzyme system in the liver endoplasmic reticulum was able to metabolize oxidatively certain xenobiotic compounds. Later that year, Hayaishi and co-workers showed that dioxygenase reactions were possible in liver microsomal preparations (Hayaishi et al., 1955) whereas Mason et al. (1955) demonstrated that monooxygenase activity was present in the same system, which utilized NADPH as a reductant. However, the detection of a carbon monoxide (CO) binding pigment in liver microsomes, giving an absorption maximum at 450 nm, was made independently by Garfinkel (1958) and Klingenberg (1958), who are generally accredited with the discovery of P450. Omura and Sato were later able to demonstrate that this pigment was, in fact, a hemoprotein of the b-type cytochrome class (Omura and Sato, 1964a and b) and these co-workers first coined the term cytochrome P450, after the wavelength of the UV absorption maximum (Figure 1.1) in the optical spectrum for the CO complex of the cytochrome pigment (Omura and Sato, 1962). These workers and others subsequently showed that the position of the characteristic Soret band could be shifted by the binding of substrates to the enzyme (Schenkman et al. 1967a and b; Schenkman, 1970) or by treatment with detergent (Omura and Sato, 1962); the latter bringing about a conversion to an inactive solubilized form of the enzyme which produced an absorption maximum at 420 nm in the CO-difference spectrum. The effect of substrate binding on the UV absorption characteristics of cytochrome P450 was of particular importance, as it appeared that different types of substrate elicited differing varieties of spectral change; namely, types I, II and modified type II (Schenkman et al., 1967a and b; Schenkman, 1970; Schenkman et al., 1972).