CYP450perhe

CYP450, or cytochrome P450, refers to a large superfamily of heme-containing monooxygenase enzymes that oxidize a wide range of substrates, including drugs, environmental chemicals, and endogenous compounds. The name derives from the visible absorbance peak at 450 nm of the reduced heme when bound to carbon monoxide. In some languages, this group is referred to as the CYP450 perhe. These enzymes participate in Phase I metabolism, introducing or unmasking polar groups to facilitate excretion.

The CYP450 family is organized into families (CYP1, CYP2, CYP3, etc.) and subfamilies (for example, CYP2D6). Members within a family share at least about 40% sequence identity, while subfamilies share at least 55%. Most drug-metabolizing enzymes are microsomal, anchored to the endoplasmic reticulum, with a smaller set located in mitochondria. The major human drug-metabolizing enzymes include CYP3A4/5, CYP2D6, CYP2C9, CYP2C19, and CYP1A2.

Catalysis requires electrons donated from NADPH via cytochrome P450 reductase and often a secondary electron donor. The catalytic cycle involves substrate binding, reduction of the heme iron, oxygen binding, a second reduction, and the formation of a reactive iron-oxo species that hydroxylates the substrate. This chemistry enables transformation of lipophilic compounds into more water-soluble metabolites for excretion.

Clinically, CYP450 enzymes govern much of drug clearance. Genetic polymorphisms lead to interindividual variability: phenotypes ranging from poor to ultra-rapid metabolizers, affecting drug efficacy and toxicity. Activity can be increased by inducers (e.g., rifampin, phenobarbital) or decreased by inhibitors (e.g., ketoconazole, cimetidine) or by dietary factors such as grapefruit juice acting on intestinal CYP3A4. Endogenous roles include steroid and fatty acid metabolism.