CYTOCHROME P450 – ROLE IN DRUG METABOLISM AND GENETIC POLYMORPHISM

The cytochrome P450 isoenzymes are a super family of haemoproteins that are terminal oxidases of mixed function oxidase system embedded primarily in the lipid bilayer of the endoplasmic reticulum (ER) of hepatocytes. They are so named because they are bound to membrane within a cell (cyto) and contain a haeme pigment (chrome P) that absorb light at a wavelength 450 nm when exposed to carbon monoxide. They are essential for metabolism of large number of endogenous and exogenous compounds. It has been estimated that 90% of human drug oxidation can be attributed to six main enzymes CYP 1A2, CYP 2C9, CYP 2C19, CYP 2D6, CYP 2E1 and CYP 3A4/5 with the two most significant enzymes being CYP 3A4 and CYP 2D6. Recently, the cytochrome isoenzymes have been shown to be important in the synthesis of steroid hormones, bile acids, arachidonic acid and in CNS function. Cytochrome P450 enzymes can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause anticipated adverse drug reactions or therapeutic failure. Genetic variability (polymorphism) in the enzymes may influence a patient's response to commonly prescribed drugs. Genotype tests for cytochrome P450 polymorphism have primarily been used for research purpose or clinical drug trials. Keywords: cytochrome P450, endoplasmic reticulum, metabolism, isoenzymes, polymorphism.