Cytochrome P450 Oxidase (CYP2E1)

Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1.14 (http://us.expasy.org/cgi-bin/get-enzyme-entry-unprecise?1.14.-.-)) important in vertebrate physiology. The cytochrome P450 mixed-function monooxygenase system is probably the most important element of Phase I metabolism in mammals.

Most are located in the endoplasmic reticulum of liver cells where they metabolize thousands of endogenous and exogenous toxins, drugs, xenobiotics, and other unneeded and potentially harmful molecules. They are, however, present in other tissues of the body including the mucosa of the gastrointestinal tract. In most animals, including humans, hepatic cytochrome P450s are the most widely studied of the P450 enzymes.

The name stands for "pigment 450" or "pink 450", so named because they absorb light of wavelengths near 450 nm when bound to carbon monoxide, giving the complexes a pink colour.

Molecular biology

Mammalian cytochrome P450 oxidases have about 500 amino acids and a heme group at the active site. Most can metabolize multiple substrates, and many can catalyze multiple reactions, which accounts for their central importance in metabolizing the potentially endless variety of foreign molecules. The cytochrome P450 monooxygenase system requires NADPH and molecular oxygen (O₂) to function.

The Human Genome Project has identified 63 human genes coding for the various cytochrome P450 enzymes.

Nomenclature

Genes encoding for the P450 enzymes, and the enzymes themselves, are designated with the abbreviation CYP, followed by an Arabic numeral indicating the gene family, a capital letter indicating the subfamily, and an Arabic numeral for the individual gene. The convention is to italicise when referring to the gene. For example, CYP2E1 is the gene which encodes for the enzyme CYP2E1 which is one of the enzymes involved in paracetamol metabolism.

CYPs involved in xenobiotic metabolism

The main CYPs involved in metabolism of compounds originating from outside the body (xenobiotics), such as drugs, include:

• CYP1A2
• CYP2B6
• CYP2C8
• CYP2C9
• CYP2C19
• CYP2D6
• CYP2E1
• CYP3A4

Other CYPs

A subset of cytochrome P450 enzymes play important roles in the synthesis of steroid hormones by the adrenals, gonads, and peripheral tissue:

• P450scc (also known as P450c11a1) in adrenal mitochondria effects “the activity formerly known as 20,22-desmolase” (20α-hydroxylase, 22-hydroxylase, cholesterol side chain scission).
• P450c11β in inner mitochondrial membrane of adrenal cortex conducts 11β-hydroxylase, 18-hydroxylase, 18-methyloxidase activities.
• P450c11AS, only in mitochondria of the adrenal zona glomerulosa conducts 11β-hydroxylase, 18-hydroxylase, 18-methyloxidase activities.
• P450c17, in endoplasmic reticulum of adrenal cortex conducts 17α-hydroxylase and 17,20-lyase activities.
• P450c21 in adrenal cortex conducts 21-hydroxylase activity.
• P450arom (aromatase) in endoplasmic reticulum of gonads, brain, adipose tissue, and elsewhere catalyzes aromatization of androgens to estrogens.