CYP1A1

Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein which in humans in encoded by the CYP1A1 gene. The protein a member of the cytochrome P450 superfamily of enzymes.

Function
CYP1A1 is involved in phase I xenobiotic and drug metabolism (one substrate of it is theophylline). It is inhibited by 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, benzopyrene (BP), by transforming it to an epoxide. In this reaction, the oxidation of benzo[a]pyrene is catalysed by CYP1A1 to form BP-7,8-epoxide, which can be further oxidized by epoxide hydrolase (EH) to form BP-7,8-dihydrodiol. Finally CYP1A1 catalyses this intermediate to form BP-7,8-dihydrodiol-9,10-epoxide, which is the ultimate carcinogen.

Regulation
The expression of the CYP1A1 and CYP1B1 genes are regulated by the aryl hydrocarbon receptor, a ligand activated transcription factor.

Polymorphisms
Several polymorphisms have been identified in CYP1A1, some of which lead to more highly inducible AHH activity. CYP1A1 polymorphisms include:
 * M1, T→C substitution at nucleotide 3801 in the 3'-non-coding region
 * M2, A→G substitution at nucleotide 2455 leading to an amino acid change of isoleucine to valine at codon 462
 * M3, T→C substitution at nucleotide 3205 in the 3'-non-coding region
 * M4, C→A substitution at nucleotide 2453 leading to an amino acid change of threonine to asparagine at codon 461