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Gene Review

CYP3A5  -  cytochrome P450, family 3, subfamily A,...

Homo sapiens

Synonyms: CP35, CYPIIIA5, Cytochrome P450 3A5, Cytochrome P450 HLp2, Cytochrome P450-PCN3, ...
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Disease relevance of CYP3A5


High impact information on CYP3A5

  • Our findings show that single-nucleotide polymorphisms (SNPs) in CYP3A5*3 and CYP3A5*6 that cause alternative splicing and protein truncation result in the absence of CYP3A5 from tissues of some people [7].
  • The three-dimensional displacement, or pharmacophore, of chemical features in space that are derived from inhibition data have produced pharmacophores for CYP3A4, CYP3A5 and CYP3A7, and provide new insights into ligand binding for each enzyme [8].
  • The MDR1 exon 26 CC genotype predicted higher day 29 etoposide clearance (P =.002) for all patients, and the CYP3A5 AA and GSTP1 AA genotypes predicted lower clearance in blacks (P =.02 and.03, respectively) [9].
  • CYP2D6 (*4 and *6) and CYP3A5 (*3) genotypes were determined from 190, 194, and 205 patient samples and in 17 living women [10].
  • METHODS: We determined cytochrome P450 (CYP)2D6 (*4 and *6) and CYP3A5 (*3) genotype from paraffin-embedded tumor samples and buccal cells (living patients) in tamoxifen-treated women enrolled onto a North Central Cancer Treatment Group adjuvant breast cancer trial [10].

Chemical compound and disease context of CYP3A5


Biological context of CYP3A5

  • In this manner, induction of CYP3A5 may contribute to the overall importance of this P450 in drug metabolism and drug interactions [15].
  • Taken together, studies here revealed the presence of a functional ER6 motif in the CYP3A5 promoter located -100 bp upstream from the transcription start site, suggesting that CYP3A5 is inducible by mechanisms similar to those involved in CYP3A4 induction [15].
  • Genetic polymorphisms in MDR1 (in exon 21 and 26), CYP3A5 (*1 and *3), and CYP3A4*1B were identified by direct sequencing [16].
  • The parameters of CPT-11 biotransformation into M2 and M4 were examined using cell lines expressing, respectively, with CYP3A4 and CYP3A5, indicating that CPT-11 is preferentially metabolized by CYP3A4 [17].
  • Sequencing data indicated that plasmids in 58 of 59 recombinant positive colonies contained an insert with a sequence identical to that present in CYP3A7 cDNA and the plasmid of only one colony contained an insert with a sequence identical to that present in CYP3A5 cDNA [18].

Anatomical context of CYP3A5


Associations of CYP3A5 with chemical compounds

  • Among the 6 subjects expressing intestinal CYP3A5, the mean saquinavir CL/F was almost twice as high as for the 14 nonexpressors (36.7 L/h [95% confidence interval (CI), 18.7-54.6 L/h] and 19.3 L/h [95% CI, 11.2-27.4 L/h], respectively; P = .03) [16].
  • CYP3A5 was induced 8-fold by dexamethasone and 11-fold by phenobarbital [22].
  • Notably, CYP3A5 had an unusually high ratio of 4- to 2-hydroxylation of 17beta-estradiol or estrone (0.53 or 1.26, respectively) [24].
  • In the absence of CYP3A5, a significant correlation was observed between 3-methoxymorphinan formation and the sample's erythromycin N-demethylase activity (r2 = 0.94, N = 12, P < 0.01), testosterone 6 beta-hydroxylase activity (r2 = 0.96, N = 7, P < 0.01) and relative immunoquantified levels of CYP3A4 (r2 = 0.96, N = 12, P < 0.01) [25].
  • The results showed that CYP3A4 and CYP3A5 contribute >95% to both testosterone 6beta-hydroxylation and diazepam 3-hydroxylation and 52 to 73% to diazepam N-demethylation, respectively [26].
  • Patients with the intestinal CYP3A5*1 genotype tended to require a higher dose of tacrolimus compared to the other group with the same hepatic CYP3A5 genotype [27].

Regulatory relationships of CYP3A5


Other interactions of CYP3A5

  • Hepatic expression of PXR correlated with that of CYP3A5 mRNA levels in a bank of liver samples [15].
  • PGC1alpha also showed a moderate activating effect on CYP3A4, CYP3A5, and CYP2D6 [32].
  • CYP3A4 and CYP3A5 had their highest mRNA expression in the duodenum (P < 0.001 and P < 0.000 001, respectively) and CYP2E1 in the stomach (P < 0.01) [33].
  • On the other hand, the expression levels of CYP2C9 and CYP3A5 mRNA showed small and variable changes in each donor even at a high concentration (50 microM) of NO-1886 [34].
  • CYP3A5 and CYP4B1 transcripts were found only in samples from premenopausal women [35].

Analytical, diagnostic and therapeutic context of CYP3A5


  1. Regulation of CYP3A genes in the human respiratory tract. Raunio, H., Hakkola, J., Pelkonen, O. Chem. Biol. Interact. (2005) [Pubmed]
  2. CYP3A4, CYP3A5, and CYP3A43 genotypes and haplotypes in the etiology and severity of prostate cancer. Zeigler-Johnson, C., Friebel, T., Walker, A.H., Wang, Y., Spangler, E., Panossian, S., Patacsil, M., Aplenc, R., Wein, A.J., Malkowicz, S.B., Rebbeck, T.R. Cancer Res. (2004) [Pubmed]
  3. Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients. Tsuchiya, N., Satoh, S., Tada, H., Li, Z., Ohyama, C., Sato, K., Suzuki, T., Habuchi, T., Kato, T. Transplantation (2004) [Pubmed]
  4. CYP3A5 genotype predicts renal CYP3A activity and blood pressure in healthy adults. Givens, R.C., Lin, Y.S., Dowling, A.L., Thummel, K.E., Lamba, J.K., Schuetz, E.G., Stewart, P.W., Watkins, P.B. J. Appl. Physiol. (2003) [Pubmed]
  5. Decreased expression of cytochrome P450 protein in non-malignant colonic tissue of patients with colonic adenoma. Bergheim, I., Bode, C., Parlesak, A. BMC gastroenterology [electronic resource]. (2005) [Pubmed]
  6. Cytochrome P450 3A5 is highly expressed in normal prostate cells but absent in prostate cancer. Leskelä, S., Honrado, E., Montero-Conde, C., Landa, I., Cascón, A., Letón, R., Talavera, P., Cózar, J.M., Concha, A., Robledo, M., Rodríguez-Antona, C. Endocr. Relat. Cancer (2007) [Pubmed]
  7. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Kuehl, P., Zhang, J., Lin, Y., Lamba, J., Assem, M., Schuetz, J., Watkins, P.B., Daly, A., Wrighton, S.A., Hall, S.D., Maurel, P., Relling, M., Brimer, C., Yasuda, K., Venkataramanan, R., Strom, S., Thummel, K., Boguski, M.S., Schuetz, E. Nat. Genet. (2001) [Pubmed]
  8. In vitro and pharmacophore insights into CYP3A enzymes. Ekins, S., Stresser, D.M., Williams, J.A. Trends Pharmacol. Sci. (2003) [Pubmed]
  9. Effects of prednisone and genetic polymorphisms on etoposide disposition in children with acute lymphoblastic leukemia. Kishi, S., Yang, W., Boureau, B., Morand, S., Das, S., Chen, P., Cook, E.H., Rosner, G.L., Schuetz, E., Pui, C.H., Relling, M.V. Blood (2004) [Pubmed]
  10. Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. Goetz, M.P., Rae, J.M., Suman, V.J., Safgren, S.L., Ames, M.M., Visscher, D.W., Reynolds, C., Couch, F.J., Lingle, W.L., Flockhart, D.A., Desta, Z., Perez, E.A., Ingle, J.N. J. Clin. Oncol. (2005) [Pubmed]
  11. Identification of a novel dexamethasone responsive enhancer in the human CYP3A5 gene and its activation in human and rat liver cells. Schuetz, J.D., Schuetz, E.G., Thottassery, J.V., Guzelian, P.S., Strom, S., Sun, D. Mol. Pharmacol. (1996) [Pubmed]
  12. Regulation of CYP3A5 by glucocorticoids and cigarette smoke in human lung-derived cells. Hukkanen, J., Väisänen, T., Lassila, A., Piipari, R., Anttila, S., Pelkonen, O., Raunio, H., Hakkola, J. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  13. Pharmacogenomics as molecular autopsy for forensic toxicology: genotyping cytochrome P450 3A4*1B and 3A5*3 for 25 fentanyl cases. Jin, M., Gock, S.B., Jannetto, P.J., Jentzen, J.M., Wong, S.H. Journal of analytical toxicology. (2005) [Pubmed]
  14. Nonlinear mixed effects model analysis of the pharmacokinetics of routinely administered bepridil in Japanese patients with arrhythmias. Taguchi, M., Fujiki, A., Iwamoto, J., Inoue, H., Tahara, K., Saigusa, K., Horiuchi, I., Oshima, Y., Hashimoto, Y. Biol. Pharm. Bull. (2006) [Pubmed]
  15. The induction of cytochrome P450 3A5 (CYP3A5) in the human liver and intestine is mediated by the xenobiotic sensors pregnane X receptor (PXR) and constitutively activated receptor (CAR). Burk, O., Koch, I., Raucy, J., Hustert, E., Eichelbaum, M., Brockmöller, J., Zanger, U.M., Wojnowski, L. J. Biol. Chem. (2004) [Pubmed]
  16. Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of cytochrome P450 3A5. Mouly, S.J., Matheny, C., Paine, M.F., Smith, G., Lamba, J., Lamba, V., Pusek, S.N., Schuetz, E.G., Stewart, P.W., Watkins, P.B. Clin. Pharmacol. Ther. (2005) [Pubmed]
  17. Metabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans. Santos, A., Zanetta, S., Cresteil, T., Deroussent, A., Pein, F., Raymond, E., Vernillet, L., Risse, M.L., Boige, V., Gouyette, A., Vassal, G. Clin. Cancer Res. (2000) [Pubmed]
  18. Functional cytochrome P4503A isoforms in human embryonic tissues: expression during organogenesis. Yang, H.Y., Lee, Q.P., Rettie, A.E., Juchau, M.R. Mol. Pharmacol. (1994) [Pubmed]
  19. Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: response to cytochrome P-450 inducers and autoinduction by oxazaphosphorines. Chang, T.K., Yu, L., Maurel, P., Waxman, D.J. Cancer Res. (1997) [Pubmed]
  20. Characterisation of CYP3A gene subfamily expression in human gastrointestinal tissues. McKinnon, R.A., Burgess, W.M., Hall, P.M., Roberts-Thomson, S.J., Gonzalez, F.J., McManus, M.E. Gut (1995) [Pubmed]
  21. Expression of enzymatically active CYP3A4 by Caco-2 cells grown on extracellular matrix-coated permeable supports in the presence of 1alpha,25-dihydroxyvitamin D3. Schmiedlin-Ren, P., Thummel, K.E., Fisher, J.M., Paine, M.F., Lown, K.S., Watkins, P.B. Mol. Pharmacol. (1997) [Pubmed]
  22. Induction and regulation of xenobiotic-metabolizing cytochrome P450s in the human A549 lung adenocarcinoma cell line. Hukkanen, J., Lassila, A., Päivärinta, K., Valanne, S., Sarpo, S., Hakkola, J., Pelkonen, O., Raunio, H. Am. J. Respir. Cell Mol. Biol. (2000) [Pubmed]
  23. CYP3A gene expression in human gut epithelium. Kolars, J.C., Lown, K.S., Schmiedlin-Ren, P., Ghosh, M., Fang, C., Wrighton, S.A., Merion, R.M., Watkins, P.B. Pharmacogenetics (1994) [Pubmed]
  24. Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Lee, A.J., Cai, M.X., Thomas, P.E., Conney, A.H., Zhu, B.T. Endocrinology (2003) [Pubmed]
  25. Characterization of dextromethorphan N-demethylation by human liver microsomes. Contribution of the cytochrome P450 3A (CYP3A) subfamily. Gorski, J.C., Jones, D.R., Wrighton, S.A., Hall, S.D. Biochem. Pharmacol. (1994) [Pubmed]
  26. Role of a potent inhibitory monoclonal antibody to cytochrome P-450 3A4 in assessment of human drug metabolism. Mei, Q., Tang, C., Assang, C., Lin, Y., Slaughter, D., Rodrigues, A.D., Baillie, T.A., Rushmore, T.H., Shou, M. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  27. Effect of intestinal CYP3A5 on postoperative tacrolimus trough levels in living-donor liver transplant recipients. Uesugi, M., Masuda, S., Katsura, T., Oike, F., Takada, Y., Inui, K. Pharmacogenet. Genomics (2006) [Pubmed]
  28. CYP3A7 protein expression is high in a fraction of adult human livers and partially associated with the CYP3A7*1C allele. Sim, S.C., Edwards, R.J., Boobis, A.R., Ingelman-Sundberg, M. Pharmacogenet. Genomics (2005) [Pubmed]
  29. Haloperidol half-life after chronic dosing. de Leon, J., Diaz, F.J., Wedlund, P., Josiassen, R.C., Cooper, T.B., Simpson, G.M. Journal of clinical psychopharmacology. (2004) [Pubmed]
  30. Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Yamakoshi, Y., Kishimoto, T., Sugimura, K., Kawashima, H. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  31. Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine. Aoyama, T., Yamano, S., Waxman, D.J., Lapenson, D.P., Meyer, U.A., Fischer, V., Tyndale, R., Inaba, T., Kalow, W., Gelboin, H.V. J. Biol. Chem. (1989) [Pubmed]
  32. Transcriptional Activation of CYP2C9, CYP1A1, and CYP1A2 by Hepatocyte Nuclear Factor 4{alpha} Requires Coactivators Peroxisomal Proliferator Activated Receptor-{gamma} Coactivator 1{alpha} and Steroid Receptor Coactivator 1. Mart??nez-Jim??nez, C.P., Castell, J.V., G??mez-Lech??n, M.J., Jover, R. Mol. Pharmacol. (2006) [Pubmed]
  33. Cytochromes P450 and MDR1 mRNA expression along the human gastrointestinal tract. Thörn, M., Finnström, N., Lundgren, S., Rane, A., Lööf, L. British journal of clinical pharmacology. (2005) [Pubmed]
  34. Assessment of induction of cytochrome P450 by NO-1886 (ibrolipim), a lipoprotein lipase-promoting agent, in primary cultures of human hepatocytes and in female rat liver. Morioka, Y., Nishimura, M., Imai, T., Suzuki, S., Harada, M., Satoh, T., Naito, S. Drug Metab. Pharmacokinet. (2006) [Pubmed]
  35. Expression of cytochrome P450 genes encoding enzymes active in the metabolism of tamoxifen in human uterine endometrium. Hukkanen, J., Mäntylä, M., Kangas, L., Wirta, P., Hakkola, J., Paakki, P., Evisalmi, S., Pelkonen, O., Raunio, H. Pharmacol. Toxicol. (1998) [Pubmed]
  36. Genetic polymorphisms of cytochrome P450 among patients with Balkan endemic nephropathy (BEN). Atanasova, S.Y., von Ahsen, N., Toncheva, D.I., Dimitrov, T.G., Oellerich, M., Armstrong, V.W. Clin. Biochem. (2005) [Pubmed]
  37. Inhibition of human intestinal wall metabolism by macrolide antibiotics: effect of clarithromycin on cytochrome P450 3A4/5 activity and expression. Pinto, A.G., Wang, Y.H., Chalasani, N., Skaar, T., Kolwankar, D., Gorski, J.C., Liangpunsakul, S., Hamman, M.A., Arefayene, M., Hall, S.D. Clin. Pharmacol. Ther. (2005) [Pubmed]
  38. Bimodal distribution of renal cytochrome P450 3A activity in humans. Haehner, B.D., Gorski, J.C., Vandenbranden, M., Wrighton, S.A., Janardan, S.K., Watkins, P.B., Hall, S.D. Mol. Pharmacol. (1996) [Pubmed]
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