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Pathway Description
Phenytoin (Antiarrhythmic) Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2013-08-22
Last Updated: 2025-01-29
This pathway illustrates the phenytoin targets involved in antiarrhythmic therapy. Contractile activity of cardiac myocytes is elicited via action potentials mediated by a number of ion channel proteins. During rest, or diastole, cells maintain a negative membrane potential; i.e. the inside the cell is negatively charged relative to the cells’ extracellular environment. Membrane ion pumps, such as the sodium-potassium ATPase and sodium-calcium exchanger (NCX), maintain low intracellular sodium (5 mM) and calcium (100 nM) concentrations and high intracellular potassium (140 mM) concentrations. Conversely, extracellular concentrations of sodium (140 mM) and calcium (1.8 mM) are relatively high and extracellular potassium concentrations are low (5 mM). At rest, the cardiac cell membrane is impermeable to sodium and calcium ions, but is permeable to potassium ions via inward rectifier potassium channels (I-K1), which allow an outward flow of potassium ions down their concentration gradient. The positive outflow of potassium ions aids in maintaining the negative intracellular electric potential. When cells reach a critical threshold potential, voltage-gated sodium channels (I-Na) open and the rapid influx of positive sodium ions into the cell occurs as the ions travel down their electrochemical gradient. This is known as the rapid depolarization or upstroke phase of the cardiac action potential. Sodium channels then close and rapidly activated potassium channels such as the voltage-gated transient outward delayed rectifying potassium channel (I-Kto) and the voltage-gated ultra rapid delayed rectifying potassium channel (I-Kur) open. These events make up the early repolarization phase during which potassium ions flow out of the cell and sodium ions are continually pumped out. During the next phase, known as the plateau phase, calcium L-type channels (I-CaL) open and the resulting influx of calcium ions roughly balances the outward flow of potassium channels. During the final repolarization phase, the voltage-gated rapid (I-Kr) and slow (I-Ks) delayed rectifying potassium channels open increasing the outflow of potassium ions and repolarizing the cell. The extra sodium and calcium ions that entered the cell during the action potential are extruded via sodium-potassium ATPases and NCX and intra- and extracellular ion concentrations are restored. In specialized pacemaker cells, gradual depolarization to threshold occurs via funny channels (I-f).
Phenytoin is an antiepileptic drug that exhibits Class 1B antiarrhythmic activity. Although phenytoin is used to treat epileptic seizures, beneficial antiarrhythmic effects have also been observed. Phenytoin preferentially binds to sodium channels (I-Na) in their inactive state. This causes a slight delay in the rapid depolarization phase of cardiac myocyte action potentials. In contrast to Class 1A antiarrhythmic drugs (e.g. quinidine) which prolong action potential duration, phenytoin and other Class 1B antiarrhythmics reduce the refractory period or action potential duration due to their membrane stabilizing effects. Phenytoin has been found to be beneficial in the treatment of atrial and ventricular arrhythmias.
References
Phenytoin (Antiarrhythmic) Pathway References
Dhein, S. Antiarrhythmic drugs. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology. (2004) p.49-51. Berlin, Germany: Springer.
Nattel S, Carlsson L: Innovative approaches to anti-arrhythmic drug therapy. Nat Rev Drug Discov. 2006 Dec;5(12):1034-49. doi: 10.1038/nrd2112.
Pubmed: 17139288
Ou Y, Gibbons SJ, Miller SM, Strege PR, Rich A, Distad MA, Ackerman MJ, Rae JL, Szurszewski JH, Farrugia G: SCN5A is expressed in human jejunal circular smooth muscle cells. Neurogastroenterol Motil. 2002 Oct;14(5):477-86.
Pubmed: 12358675
Ye B, Valdivia CR, Ackerman MJ, Makielski JC: A common human SCN5A polymorphism modifies expression of an arrhythmia causing mutation. Physiol Genomics. 2003 Feb 6;12(3):187-93. doi: 10.1152/physiolgenomics.00117.2002.
Pubmed: 12454206
Wang J, Ou SW, Wang YJ, Kameyama M, Kameyama A, Zong ZH: Analysis of four novel variants of Nav1.5/SCN5A cloned from the brain. Neurosci Res. 2009 Aug;64(4):339-47. doi: 10.1016/j.neures.2009.04.003. Epub 2009 Apr 17.
Pubmed: 19376164
Ahn AH, Freener CA, Gussoni E, Yoshida M, Ozawa E, Kunkel LM: The three human syntrophin genes are expressed in diverse tissues, have distinct chromosomal locations, and each bind to dystrophin and its relatives. J Biol Chem. 1996 Feb 2;271(5):2724-30. doi: 10.1074/jbc.271.5.2724.
Pubmed: 8576247
Ort T, Maksimova E, Dirkx R, Kachinsky AM, Berghs S, Froehner SC, Solimena M: The receptor tyrosine phosphatase-like protein ICA512 binds the PDZ domains of beta2-syntrophin and nNOS in pancreatic beta-cells. Eur J Cell Biol. 2000 Sep;79(9):621-30.
Pubmed: 11043403
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Ahn AH, Yoshida M, Anderson MS, Feener CA, Selig S, Hagiwara Y, Ozawa E, Kunkel LM: Cloning of human basic A1, a distinct 59-kDa dystrophin-associated protein encoded on chromosome 8q23-24. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4446-50. doi: 10.1073/pnas.91.10.4446.
Pubmed: 8183929
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Castello A, Brocheriou V, Chafey P, Kahn A, Gilgenkrantz H: Characterization of the dystrophin-syntrophin interaction using the two-hybrid system in yeast. FEBS Lett. 1996 Mar 25;383(1-2):124-8. doi: 10.1016/0014-5793(96)00214-1.
Pubmed: 8612778
Hasegawa M, Cuenda A, Spillantini MG, Thomas GM, Buee-Scherrer V, Cohen P, Goedert M: Stress-activated protein kinase-3 interacts with the PDZ domain of alpha1-syntrophin. A mechanism for specific substrate recognition. J Biol Chem. 1999 Apr 30;274(18):12626-31. doi: 10.1074/jbc.274.18.12626.
Pubmed: 10212242
Miyazawa M, Shindo M, Shimada T: Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes. Drug Metab Dispos. 2002 May;30(5):602-7. doi: 10.1124/dmd.30.5.602.
Pubmed: 11950794
Ibeanu GC, Goldstein JA, Meyer U, Benhamou S, Bouchardy C, Dayer P, Ghanayem BI, Blaisdell J: Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin. J Pharmacol Exp Ther. 1998 Sep;286(3):1490-5.
Pubmed: 9732415
Ibeanu GC, Blaisdell J, Ghanayem BI, Beyeler C, Benhamou S, Bouchardy C, Wilkinson GR, Dayer P, Daly AK, Goldstein JA: An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians. Pharmacogenetics. 1998 Apr;8(2):129-35.
Pubmed: 10022751
Meehan RR, Gosden JR, Rout D, Hastie ND, Friedberg T, Adesnik M, Buckland R, van Heyningen V, Fletcher J, Spurr NK, et al.: Human cytochrome P-450 PB-1: a multigene family involved in mephenytoin and steroid oxidations that maps to chromosome 10. Am J Hum Genet. 1988 Jan;42(1):26-37.
Pubmed: 2827463
Kimura S, Pastewka J, Gelboin HV, Gonzalez FJ: cDNA and amino acid sequences of two members of the human P450IIC gene subfamily. Nucleic Acids Res. 1987 Dec 10;15(23):10053-4. doi: 10.1093/nar/15.23.10053.
Pubmed: 3697070
Ikeya K, Jaiswal AK, Owens RA, Jones JE, Nebert DW, Kimura S: Human CYP1A2: sequence, gene structure, comparison with the mouse and rat orthologous gene, and differences in liver 1A2 mRNA expression. Mol Endocrinol. 1989 Sep;3(9):1399-408. doi: 10.1210/mend-3-9-1399.
Pubmed: 2575218
Jaiswal AK, Nebert DW, Gonzalez FJ: Human P3(450): cDNA and complete amino acid sequence. Nucleic Acids Res. 1986 Aug 26;14(16):6773-4. doi: 10.1093/nar/14.16.6773.
Pubmed: 3755823
Quattrochi LC, Pendurthi UR, Okino ST, Potenza C, Tukey RH: Human cytochrome P-450 4 mRNA and gene: part of a multigene family that contains Alu sequences in its mRNA. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6731-5. doi: 10.1073/pnas.83.18.6731.
Pubmed: 3462722
Hu Y, Oscarson M, Johansson I, Yue QY, Dahl ML, Tabone M, Arinco S, Albano E, Ingelman-Sundberg M: Genetic polymorphism of human CYP2E1: characterization of two variant alleles. Mol Pharmacol. 1997 Mar;51(3):370-6.
Pubmed: 9058590
Fairbrother KS, Grove J, de Waziers I, Steimel DT, Day CP, Crespi CL, Daly AK: Detection and characterization of novel polymorphisms in the CYP2E1 gene. Pharmacogenetics. 1998 Dec;8(6):543-52.
Pubmed: 9918138
Song BJ, Gelboin HV, Park SS, Yang CS, Gonzalez FJ: Complementary DNA and protein sequences of ethanol-inducible rat and human cytochrome P-450s. Transcriptional and post-transcriptional regulation of the rat enzyme. J Biol Chem. 1986 Dec 15;261(35):16689-97.
Pubmed: 3782137
Striated Muscle Contraction References
Cooke R: The sliding filament model: 1972-2004. J Gen Physiol. 2004 Jun;123(6):643-56. doi: 10.1085/jgp.200409089.
Pubmed: 15173218
Szent-Gyorgyi A: The mechanism of muscle contraction. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3343-4.
Pubmed: 4610574
Kuo IY, Ehrlich BE: Signaling in muscle contraction. Cold Spring Harb Perspect Biol. 2015 Feb 2;7(2):a006023. doi: 10.1101/cshperspect.a006023.
Pubmed: 25646377
Ou Y, Gibbons SJ, Miller SM, Strege PR, Rich A, Distad MA, Ackerman MJ, Rae JL, Szurszewski JH, Farrugia G: SCN5A is expressed in human jejunal circular smooth muscle cells. Neurogastroenterol Motil. 2002 Oct;14(5):477-86.
Pubmed: 12358675
Ye B, Valdivia CR, Ackerman MJ, Makielski JC: A common human SCN5A polymorphism modifies expression of an arrhythmia causing mutation. Physiol Genomics. 2003 Feb 6;12(3):187-93. doi: 10.1152/physiolgenomics.00117.2002.
Pubmed: 12454206
Wang J, Ou SW, Wang YJ, Kameyama M, Kameyama A, Zong ZH: Analysis of four novel variants of Nav1.5/SCN5A cloned from the brain. Neurosci Res. 2009 Aug;64(4):339-47. doi: 10.1016/j.neures.2009.04.003. Epub 2009 Apr 17.
Pubmed: 19376164
Ahn AH, Freener CA, Gussoni E, Yoshida M, Ozawa E, Kunkel LM: The three human syntrophin genes are expressed in diverse tissues, have distinct chromosomal locations, and each bind to dystrophin and its relatives. J Biol Chem. 1996 Feb 2;271(5):2724-30. doi: 10.1074/jbc.271.5.2724.
Pubmed: 8576247
Ort T, Maksimova E, Dirkx R, Kachinsky AM, Berghs S, Froehner SC, Solimena M: The receptor tyrosine phosphatase-like protein ICA512 binds the PDZ domains of beta2-syntrophin and nNOS in pancreatic beta-cells. Eur J Cell Biol. 2000 Sep;79(9):621-30.
Pubmed: 11043403
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Ahn AH, Yoshida M, Anderson MS, Feener CA, Selig S, Hagiwara Y, Ozawa E, Kunkel LM: Cloning of human basic A1, a distinct 59-kDa dystrophin-associated protein encoded on chromosome 8q23-24. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4446-50. doi: 10.1073/pnas.91.10.4446.
Pubmed: 8183929
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Castello A, Brocheriou V, Chafey P, Kahn A, Gilgenkrantz H: Characterization of the dystrophin-syntrophin interaction using the two-hybrid system in yeast. FEBS Lett. 1996 Mar 25;383(1-2):124-8. doi: 10.1016/0014-5793(96)00214-1.
Pubmed: 8612778
Hasegawa M, Cuenda A, Spillantini MG, Thomas GM, Buee-Scherrer V, Cohen P, Goedert M: Stress-activated protein kinase-3 interacts with the PDZ domain of alpha1-syntrophin. A mechanism for specific substrate recognition. J Biol Chem. 1999 Apr 30;274(18):12626-31. doi: 10.1074/jbc.274.18.12626.
Pubmed: 10212242
Miyazawa M, Shindo M, Shimada T: Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes. Drug Metab Dispos. 2002 May;30(5):602-7. doi: 10.1124/dmd.30.5.602.
Pubmed: 11950794
Ibeanu GC, Goldstein JA, Meyer U, Benhamou S, Bouchardy C, Dayer P, Ghanayem BI, Blaisdell J: Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin. J Pharmacol Exp Ther. 1998 Sep;286(3):1490-5.
Pubmed: 9732415
Ibeanu GC, Blaisdell J, Ghanayem BI, Beyeler C, Benhamou S, Bouchardy C, Wilkinson GR, Dayer P, Daly AK, Goldstein JA: An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians. Pharmacogenetics. 1998 Apr;8(2):129-35.
Pubmed: 10022751
Meehan RR, Gosden JR, Rout D, Hastie ND, Friedberg T, Adesnik M, Buckland R, van Heyningen V, Fletcher J, Spurr NK, et al.: Human cytochrome P-450 PB-1: a multigene family involved in mephenytoin and steroid oxidations that maps to chromosome 10. Am J Hum Genet. 1988 Jan;42(1):26-37.
Pubmed: 2827463
Kimura S, Pastewka J, Gelboin HV, Gonzalez FJ: cDNA and amino acid sequences of two members of the human P450IIC gene subfamily. Nucleic Acids Res. 1987 Dec 10;15(23):10053-4. doi: 10.1093/nar/15.23.10053.
Pubmed: 3697070
Ikeya K, Jaiswal AK, Owens RA, Jones JE, Nebert DW, Kimura S: Human CYP1A2: sequence, gene structure, comparison with the mouse and rat orthologous gene, and differences in liver 1A2 mRNA expression. Mol Endocrinol. 1989 Sep;3(9):1399-408. doi: 10.1210/mend-3-9-1399.
Pubmed: 2575218
Jaiswal AK, Nebert DW, Gonzalez FJ: Human P3(450): cDNA and complete amino acid sequence. Nucleic Acids Res. 1986 Aug 26;14(16):6773-4. doi: 10.1093/nar/14.16.6773.
Pubmed: 3755823
Quattrochi LC, Pendurthi UR, Okino ST, Potenza C, Tukey RH: Human cytochrome P-450 4 mRNA and gene: part of a multigene family that contains Alu sequences in its mRNA. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6731-5. doi: 10.1073/pnas.83.18.6731.
Pubmed: 3462722
Hu Y, Oscarson M, Johansson I, Yue QY, Dahl ML, Tabone M, Arinco S, Albano E, Ingelman-Sundberg M: Genetic polymorphism of human CYP2E1: characterization of two variant alleles. Mol Pharmacol. 1997 Mar;51(3):370-6.
Pubmed: 9058590
Fairbrother KS, Grove J, de Waziers I, Steimel DT, Day CP, Crespi CL, Daly AK: Detection and characterization of novel polymorphisms in the CYP2E1 gene. Pharmacogenetics. 1998 Dec;8(6):543-52.
Pubmed: 9918138
Song BJ, Gelboin HV, Park SS, Yang CS, Gonzalez FJ: Complementary DNA and protein sequences of ethanol-inducible rat and human cytochrome P-450s. Transcriptional and post-transcriptional regulation of the rat enzyme. J Biol Chem. 1986 Dec 15;261(35):16689-97.
Pubmed: 3782137
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