CYP1A2

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Cytochrome P450, family 1, subfamily A, polypeptide 2

PDB rendering based on 2hi4.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CYP1A2 ; CP12; P3-450; P450(PA)
External IDs OMIM124060 MGI88589 HomoloGene68082 ChEMBL: 3356 GeneCards: CYP1A2 Gene
EC number 1.14.14.1
RNA expression pattern
PBB GE CYP1A2 207609 s at tn.png
PBB GE CYP1A2 207608 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1544 13077
Ensembl ENSG00000140505 ENSMUSG00000032310
UniProt P05177 P00186
RefSeq (mRNA) NM_000761 NM_009993
RefSeq (protein) NP_000752 NP_034123
Location (UCSC) Chr 15:
75.04 – 75.05 Mb
Chr 9:
57.68 – 57.68 Mb
PubMed search [1] [2]

Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body.[1] In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene.[2]

Function[edit]

CYP1A2 is a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. CYP1A2 localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and acetaminophen. The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region.[3]

Effect of diet[edit]

Expression of CYP1A2 appears to be induced by various dietary constituents.[4] Vegetables such as cabbages, cauliflower and broccoli are known to increase levels of CYP1A2. Lower activity of CYP1A2 in South Asians appears to be due to cooking these vegetables in curries using ingredients such as cumin and turmeric, ingredients known to inhibit the enzyme.[5]

Ligands[edit]

Following is a table of selected substrates, inducers and inhibitors of CYP1A2.

Inhibitors of CYP1A2 can be classified by their potency, such as:

  • Strong inhibitor being one that causes at least a 5-fold increase in the plasma AUC values, or more than 80% decrease in clearance.[6]
  • Moderate inhibitor being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance.[6]
  • Weak inhibitor being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20-50% decrease in clearance.[6]
Substrates Inhibitors Inducers
Strong:

Weak

Unspecified potency:

References[edit]

  1. ^ Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, Nebert DW (January 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. doi:10.1097/00008571-200401000-00001. PMID 15128046. 
  2. ^ Jaiswal AK, Nebert DW, McBride OW, Gonzalez FJ (1987). "Human P(3)450: cDNA and complete protein sequence, repetitive Alu sequences in the 3' nontranslated region, and localization of gene to chromosome 15". J. Exp. Pathol. 3 (1): 1–17. PMID 3681487. 
  3. ^ "Entrez Gene: cytochrome P450". 
  4. ^ Fontana R, Lown K, Paine M, Fortlage L, Santella R, Felton J, Knize M, Greenberg A, Watkins P (1999). "Effects of a chargrilled meat diet on expression of CYP3A, CYP1A, and P-glycoprotein levels in healthy volunteers". Gastroenterology 117 (1): 89–98. doi:10.1016/S0016-5085(99)70554-8. PMID 10381914. 
  5. ^ a b c d e Sanday, Kate (17 October 2011), "South Asians and Europeans react differently to common drugs", University of Sydney Faculty of Pharmacy News 
  6. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as Flockhart DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine.  Retrieved on July 2011
  7. ^ a b c d e f g h i j k l m n o p Swedish environmental classification of pharmaceuticals - FASS (drug catalog) - Facts for prescribers (Fakta för förskrivare). Retrieved July 2011
  8. ^ "Erlotinib". "Metabolized primarily by CYP3A4 and, to a lesser degree, by CYP1A2 and the extrahepatic isoform CYP1A1" 
  9. ^ Maliakal, Pius. "Effect of herbal teas on hepatic drug metabolizing enzymes in rats". Journal of Pharmacy and Pharmacology. Retrieved 29 December 2012. 
  10. ^ http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm
  11. ^ Edwards DJ, Bernier SM (1996). "Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man". Life Sciences 59 (13): 1025–1030. doi:10.1016/0024-3205(96)00417-1. PMC 1381556. PMID 8485024. 
  12. ^ Wen X, Wang JS, Neuvonen PJ, Backman JT. "Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes.". PMID 11868802. 
  13. ^ Gorski JC, Huang SM, Pinto A, Hamman MA, Hilligoss JK, Zaheer NA, Desai M, Miller M, Hall SD (January 2004). "The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo". Clin. Pharmacol. Ther. 75 (1): 89–100. doi:10.1016/j.clpt.2003.09.013. PMID 14749695. 

Further reading[edit]

See also[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.