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CYP1A1
Introduction
Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein[1] which in humans in encoded by the CYP1A1 gene.[2] The protein a member of the cytochrome P450 superfamily of enzymes.[3]
Function
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.[4]
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.[4]
Regulation
Regulation
The expression of the CYP1A1 and CYP1B1 genes are regulated by the aryl hydrocarbon receptor, a ligand activated transcription factor.[5]
Polymorphisms
Polymorphisms
Several polymorphisms have been identified in CYP1A1, some of which lead to more highly inducible AHH activity. CYP1A1 polymorphisms include:[6][7][8][9]
- 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
References
References
- ↑ Kawajiri K (1999). “CYP1A1”. IARC scientific publications (148): 159–72. PMID 10493257.
- ↑ Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, Nebert DW (2004). “Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants”. Pharmacogenetics. 14 (1): 1–18. PMID 15128046. Unknown parameter
|month=ignored (help) - ↑ Smith G, Stubbins MJ, Harries LW, Wolf CR (1998). “Molecular genetics of the human cytochrome P450 monooxygenase superfamily”. Xenobiotica; the fate of foreign compounds in biological systems. 28 (12): 1129–65. PMID 9890157. Unknown parameter
|month=ignored (help) - ↑ 4.0 4.1 Beresford AP (1993). “CYP1A1: friend or foe?”. Drug metabolism reviews. 25 (4): 503–17. PMID 8313840.
- ↑ Ma Q, Lu AY (2007). “CYP1A induction and human risk assessment: an evolving tale of in vitro and in vivo studies”. Drug metabolism and disposition: the biological fate of chemicals. 35 (7): 1009–16. doi:10.1124/dmd.107.015826. PMID 17431034. Unknown parameter
|month=ignored (help) - ↑ Petersen DD, McKinney CE, Ikeya K, Smith HH, Bale AE, McBride OW, Nebert DW (1991). “Human CYP1A1 gene: cosegregation of the enzyme inducibility phenotype and an RFLP”. American journal of human genetics. 48 (4): 720–5. PMC 1682951. PMID 1707592. Unknown parameter
|month=ignored (help) - ↑ Cosma G, Crofts F, Taioli E, Toniolo P, Garte S (1993). “Relationship between genotype and function of the human CYP1A1 gene”. Journal of toxicology and environmental health. 40 (2–3): 309–16. PMID 7901425.
- ↑ Crofts F, Taioli E, Trachman J, Cosma GN, Currie D, Toniolo P, Garte SJ (1994). “Functional significance of different human CYP1A1 genotypes”. Carcinogenesis. 15 (12): 2961–3. PMID 8001264. Unknown parameter
|month=ignored (help) - ↑ Kiyohara C, Hirohata T, Inutsuka S (1996). “The relationship between aryl hydrocarbon hydroxylase and polymorphisms of the CYP1A1 gene”. Japanese journal of cancer research : Gann. 87 (1): 18–24. PMID 8609043. Unknown parameter
|month=ignored (help)
Further reading
Further reading
- Nelson DR, Zeldin DC, Hoffman SM; et al. (2004). “Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants”. Pharmacogenetics. 14 (1): 1–18. PMID 15128046.
- Masson LF, Sharp L, Cotton SC, Little J (2005). “Cytochrome P-450 1A1 gene polymorphisms and risk of breast cancer: a HuGE review”. Am. J. Epidemiol. 161 (10): 901–15. doi:10.1093/aje/kwi121. PMID 15870154.
- Hildebrandt AG, Schwarz D, Krusekopf S; et al. (2007). “Recalling P446. P4501A1 (CYP1A1) opting for clinical application”. Drug Metab. Rev. 39 (2–3): 323–41. doi:10.1080/03602530701498026. PMID 17786624.