The first experimental evidence relating to cytochromes P450 was discovered in 1955 by Axelrod  and Brodie et al. , who identified an enzyme system in the endoplasmic reticulum of the liver which was able to oxidize xenobiotic compounds. In 1958 Garfinkel  and Klingenberg  detected a CO binding pigment in liver microsomes which had an absorption maximum at 450nm (See Figure ). This was demonstrated to be a hemoprotein of the b-type class in 1964 [82, 83] which was named cytochrome P450 after the strong feature in its absorption spectrum. Electron spin resonance spectroscopy suggested that P450 is a low spin ferric hemoprotein  with a thiol residue as an axial haem ligand [85, 86, 87]. This lead to explanations for the unusual Soret peak position and its perturbation upon the binding of substrates and other chemicals in terms of charge transfer modulated by the Fe - S bond [88, 89, 90]. Raman spectroscopy provided confirmation of the presence of an Fe - S bond and identified this as a covalently bonded cysteine residue . In 1985 a full structure of (CYP101), a bacterial P450 from Pseudomonas putida, was obtained [92, 93]. Subsequently, crystal structures have been obtained for the  and enzymes  as well as for in complex with substrate , carbon monoxide , inhibitors [98, 99] and substrate analogues [100, 101, 102].
Figure: The absorption spectrum of cytochrome P450-CO complex showing the characteristic Soret peak at approximately 450nm (Created using data from  for ).
The first metabolic pathway shown to involve P450 was that for C21-hydroxylation of steroids in the adrenal corticoid system [103, 104]. Its rôle as the terminal oxidase was confirmed for the liver microsomal system in the endoplasmic reticulum .
Originally discovered in mammalian liver microsomal preparations, P450s have subsequently been discovered in every class of biotica. In addition, although found mainly in the liver , P450s have been identified in many other organs . P450s are responsible for the metabolism of numerous endogenous compounds [107, 108] as well as an enormous range of xenobiotic compounds  including many toxins and carcinogens  as well as drugs.