CYP1A2
Ensembl | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 15: 74.75 – 74.76 Mb | Chr 9: 57.58 – 57.59 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body.[5] In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene.[6]
Function
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 paracetamol (acetaminophen). The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region.[7]
CYP1A2 also metabolizes
20-hydroxyeicosatetraenoic acid) but also has epoxygenase activity in that it metabolizes docosahexaenoic acid to epoxides, primarily 19R,20S-epoxyeicosapentaenoic acid and 19S,20R-epoxyeicosapentaenoic acid isomers (termed 19,20-EDP) and similarly metabolizes eicosapentaenoic acid to epoxides, primarily 17R,18S-eicosatetraenoic acid and 17S,18R-eicosatetraenoic acid isomers (termed 17,18-EEQ).[8]
19-HETE is an inhibitor of 20-HETE, a broadly active signaling molecule, e.g., it constricts
soluble epoxide hydrolase
, and therefore act locally.
CYP1A2 is not regarded as being a major contributor to forming the aforementioned epoxides[12] but could act locally in certain tissues to do so.
The authoritative list of star allele nomenclature for CYP1A2 along with activity scores is kept by PharmVar.[14]
Effect of diet
Expression of CYP1A2 appears to be induced by various dietary constituents.[15] 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.[16]
CYP1A2 is also involved in the metabolization of caffeine, and the presence of alleles that make this metabolization slow have been associated with an increased risk of nonfatal myocardial infarction for those who drink a lot of coffee (4 or more cups per day).[17]
Ligands
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 clearance thereof.[18]
- Moderate inhibitor being one that causes at least a 2-fold increase in the plasma AUC values of sensitive substrates metabolized through CYP1A2, or 50-80% decrease in clearance thereof.[18]
- Weak inhibitor being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values of sensitive substrates metabolized through CYP1A2, or 20-50% decrease in clearance thereof.[18]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000140505 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032310 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 18448751.
- PMID 3681487.
- ^ "Entrez Gene: cytochrome P450". Archived from the original on 10 May 2009. Retrieved 30 August 2017.
- PMID 21945326.
- ^ PMID 25244930.
- PMID 24345640.
- PMID 26621325.
- ^ PMID 25240260.
- PMID 24634501.
- ^
This article incorporates public domain material from "PharmVar". Reference Sequence collection. National Center for Biotechnology Information. Retrieved 20 May 2020.
- PMID 10381914.
- ^ a b c d e Sanday K (17 October 2011), "South Asians and Europeans react differently to common drugs", University of Sydney Faculty of Pharmacy News, archived from the original on 9 March 2014, retrieved 24 October 2011
- PMID 16522833.
- ^ a b c Center for Drug Evaluation and Research. "Drug Interactions & Labeling - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers". www.fda.gov. Archived from the original on 10 May 2016. Retrieved 1 June 2016.
- ^ .
- ^ a b c d e f g h i j k l m n o p q r s t u v "Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers". FDA. 26 May 2021. Archived from the original on 4 November 2020. Retrieved 22 June 2020.
- S2CID 233470717.
- ^ 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 Flockhart DA (2007). "Drug Interactions Flockhart Table". Indiana University School of Medicine. Archived from the original on 30 August 2007. Retrieved 22 June 2020.
- ^ FASS (drug catalog)- Facts for prescribers (Fakta för förskrivare). Retrieved July 2011
- from the original on 21 June 2021. Retrieved 15 November 2021.
Ninety percent of melatonin is metabolized in the liver primarily by the enzyme CYP1A2
- ^ "Erlotinib". Archived from the original on 24 December 2019. Retrieved 10 April 2018.
Metabolized primarily by CYP3A4 and, to a lesser degree, by CYP1A2 and the extrahepatic isoform CYP1A1
- ^ a b "Verapamil: Drug information. Lexicomp". UpToDate. Archived from the original on 13 January 2019. Retrieved 13 January 2019.
Metabolism/Transport Effects: Substrate of CYP1A2 (minor), CYP2B6 (minor), CYP2C9 (minor), CYP2E1 (minor), CYP3A4 (major), P-glycoprotein/ABCB1; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (weak), CYP3A4 (moderate), P-glycoprotein/ABCB1
- PMID 28774812.
- PMID 22286810.
- ^ "Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers". U.S. Food and Drug Administration. 9 February 2019. Archived from the original on 10 May 2016. Retrieved 16 December 2019.
- S2CID 8375888.
- ^ PMID 30558213.
- PMID 8485024.
- S2CID 19299097.
- S2CID 24002845.
- PMID 33951339.
Further reading
- Meijerman I, Beijnen JH, Schellens JH (2006). "Herb-drug interactions in oncology: focus on mechanisms of induction". The Oncologist. 11 (7): 742–752. PMID 16880233.
- Smith G, Stubbins MJ, Harries LW, Wolf CR (December 1998). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 28 (12): 1129–1165. PMID 9890157.
- Landi MT, Sinha R, Lang NP, Kadlubar FF (1999). "Human cytochrome P4501A2". IARC Scientific Publications (148): 173–195. PMID 10493258.
- Ikeya K, Jaiswal AK, Owens RA, Jones JE, Nebert DW, Kimura S (September 1989). "Human CYP1A2: sequence, gene structure, comparison with the mouse and rat orthologous gene, and differences in liver 1A2 mRNA expression". Molecular Endocrinology. 3 (9): 1399–1408. PMID 2575218.
- Butler MA, Iwasaki M, Guengerich FP, Kadlubar FF (October 1989). "Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines". Proceedings of the National Academy of Sciences of the United States of America. 86 (20): 7696–7700. PMID 2813353.
- Quattrochi LC, Okino ST, Pendurthi UR, Tukey RH (October 1985). "Cloning and isolation of human cytochrome P-450 cDNAs homologous to dioxin-inducible rabbit mRNAs encoding P-450 4 and P-450 6". DNA. 4 (5): 395–400. PMID 3000715.
- Quattrochi LC, Pendurthi UR, Okino ST, Potenza C, Tukey RH (September 1986). "Human cytochrome P-450 4 mRNA and gene: part of a multigene family that contains Alu sequences in its mRNA". Proceedings of the National Academy of Sciences of the United States of America. 83 (18): 6731–6735. PMID 3462722.
- Wrighton SA, Campanile C, Thomas PE, Maines SL, Watkins PB, Parker G, Mendez-Picon G, Haniu M, Shively JE, Levin W (April 1986). "Identification of a human liver cytochrome P-450 homologous to the major isosafrole-inducible cytochrome P-450 in the rat". Molecular Pharmacology. 29 (4): 405–410. PMID 3517618.
- Jaiswal AK, Nebert DW, Gonzalez FJ (August 1986). "Human P3(450): cDNA and complete amino acid sequence". Nucleic Acids Research. 14 (16): 6773–6774. PMID 3755823.
- Eugster HP, Probst M, Würgler FE, Sengstag C (1993). "Caffeine, estradiol, and progesterone interact with human CYP1A1 and CYP1A2. Evidence from cDNA-directed expression in Saccharomyces cerevisiae". Drug Metabolism and Disposition. 21 (1): 43–49. PMID 8095225.
- Schweikl H, Taylor JA, Kitareewan S, Linko P, Nagorney D, Goldstein JA (October 1993). "Expression of CYP1A1 and CYP1A2 genes in human liver". Pharmacogenetics. 3 (5): 239–249. PMID 8287062.
- Yamazaki H, Inoue K, Mimura M, Oda Y, Guengerich FP, Shimada T (February 1996). "7-Ethoxycoumarin O-deethylation catalyzed by cytochromes P450 1A2 and 2E1 in human liver microsomes". Biochemical Pharmacology. 51 (3): 313–319. PMID 8573198.
- Hakkola J, Raunio H, Purkunen R, Pelkonen O, Saarikoski S, Cresteil T, Pasanen M (July 1996). "Detection of cytochrome P450 gene expression in human placenta in first trimester of pregnancy". Biochemical Pharmacology. 52 (2): 379–383. PMID 8694864.
- Guengerich FP, Johnson WW (December 1997). "Kinetics of ferric cytochrome P450 reduction by NADPH-cytochrome P450 reductase: rapid reduction in the absence of substrate and variations among cytochrome P450 systems". Biochemistry. 36 (48): 14741–14750. PMID 9398194.
- Wacke R, Kirchner A, Prall F, Nizze H, Schmidt W, Fischer U, Nitschke FP, Adam U, Fritz P, Belloc C, Drewelow B (May 1998). "Up-regulation of cytochrome P450 1A2, 2C9, and 2E1 in chronic pancreatitis". Pancreas. 16 (4): 521–528. S2CID 24670684.
- Macé K, Bowman ED, Vautravers P, Shields PG, Harris CC, Pfeifer AM (May 1998). "Characterisation of xenobiotic-metabolising enzyme expression in human bronchial mucosa and peripheral lung tissues". European Journal of Cancer. 34 (6): 914–920. PMID 9797707.
- Huang JD, Guo WC, Lai MD, Guo YL, Lambert GH (January 1999). "Detection of a novel cytochrome P-450 1A2 polymorphism (F21L) in Chinese". Drug Metabolism and Disposition. 27 (1): 98–101. PMID 9884316.
- Tatemichi M, Nomura S, Ogura T, Sone H, Nagata H, Esumi H (August 1999). "Mutagenic activation of environmental carcinogens by microsomes of gastric mucosa with intestinal metaplasia". Cancer Research. 59 (16): 3893–3898. PMID 10463577.
External links
- Human CYP1A2 genome location and CYP1A2 gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: P05177 (Cytochrome P450 1A2) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
PDB gallery | |
|---|---|
|
