CYP1A1
Description
The CYP1A1 (cytochrome P450 family 1 subfamily A member 1) is a protein-coding gene located on chromosome 15.
Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein that in humans is encoded by the CYP1A1 gene. The protein is a member of the cytochrome P450 superfamily of enzymes. CYP1A1 is involved in phase I xenobiotic and drug metabolism (one substrate of it is theophylline). It is inhibited by hesperetin (a flavonoid found in lime, sweet orange), fluoroquinolones and macrolides and induced by aromatic hydrocarbons. CYP1A1 is also known as AHH (aryl hydrocarbon hydroxylase). It is involved in the metabolic activation of aromatic hydrocarbons (polycyclic aromatic hydrocarbons, PAH), for example, benzo[a]pyrene (BaP), by transforming it to an epoxide. In this reaction, the oxidation of benzo[a]pyrene is catalysed by CYP1A1 to form BaP-7,8-epoxide, which can be further oxidized by epoxide hydrolase (EH) to form BaP-7,8-dihydrodiol. Finally, CYP1A1 catalyses this intermediate to form BaP-7,8-dihydrodiol-9,10-epoxide, which is a carcinogen. However, an in vivo experiment with gene-deficient mice has found that the hydroxylation of benzo[a]pyrene by CYP1A1 can have an overall protective effect on the DNA, rather than contributing to potentially carcinogenic DNA modifications. This effect is likely due to the fact that CYP1A1 is highly active in the intestinal mucosa, and thus inhibits infiltration of ingested benzo[a]pyrene carcinogen into the systemic circulation.
CYP1A1 is a cytochrome P450 monooxygenase that plays a role in metabolizing various endogenous substrates, including fatty acids, steroid hormones, and vitamins. It uses molecular oxygen to insert one oxygen atom into a substrate and reduce the other oxygen atom into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase. CYP1A1 catalyzes the hydroxylation of carbon-hydrogen bonds and exhibits high catalytic activity in the formation of hydroxyestrogens from estrone and 17beta-estradiol. It also displays different regioselectivities for polyunsaturated fatty acid hydroxylation and catalyzes the epoxidation of double bonds of certain polyunsaturated fatty acids. Additionally, CYP1A1 converts arachidonic acid into epoxyeicosatrienoic acid regioisomers, which function as lipid mediators in the vascular system. CYP1A1 also exhibits absolute stereoselectivity in the epoxidation of eicosapentaenoic acid, producing the 17(R),18(S) enantiomer. It may play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues, catalyzing two successive oxidative transformations of all-trans retinol into all-trans retinal and then to the active form all-trans retinoic acid. CYP1A1 may also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites.
CYP1A1 is also known as AHH, AHRR, CP11, CYP1, CYPIA1, P1-450, P450-C, P450DX.
