Cytochromes P450

The cytochromes P450 (EC 1.14.14.1) are a superfamily of heme-containing monooxygenases that catalyze a myriad of oxidative metabolic reactions upon generation of the high-valent iron-oxo species formed during the enzyme's catalytic cycle. Key characteristics of the P450s are presented in Table 1 and compared with the other drug-metabolizing enzymes under discussion.

P450s are represented in every living organism examined to date, and as of January 2005, over 4500 unique P450 sequences had been identified from animals, bacteria, fungi, and lower eukaryotes.134 The plant kingdom is particularly rich in P450 genes where they can comprise up to 1% of the plant genome.4 Mammalian species exhibit less diversity, with humans possessing 57 functional P450s which are grouped into 18 structurally related families, termed CYP1-5, CYP7-8, CYP11, CYP17, CYP19-21, CYP24, CYP26-27, CYP39, CYP46, and CYP51.5 These enzyme families are primarily associated with the metabolism of drugs and other xenobiotics or endogenous compounds such as sterols, bile acids, vitamins, and fatty acids. Several members of the CYP1, CYP2, and CYP3 families, present at relatively high concentrations in the endoplasmic reticulum of liver cells, exhibit the broadest substrate selectivity and collectively represent the 'drug-metabolizing' P450s (Table 2). See 5.05 Principles of Drug Metabolism 1: Redox Reactions for further details on redox reactions in drug metabolism.

Table 1 Human drug-metabolizing enzymes

Enzyme family

Enzymes

Subunit molecular weight (kDa)

Prosthetic group(s)/ external cofactor

Chromosomal location

Enzymes of major importance to drug metabolism/toxicity

Cytochromes P450

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