CYP3A4 is a vitamin D-24- and 25-hydroxylase: Analysis of structure function by site-directed mutagenesis

Journal of Clinical Endocrinology and Metabolism

Volumn 90, Issue 2, 2005, Pages 1210-1219

  Gupta, Ram P ^a   He, You Ai ^c   Patrick, Kennerly S ^b   Halpert, James R ^c   Bell, Norman H ^a  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^b MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^c University of Texas Medical Branch School of Medicine   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,24 DIHYDROXYVITAMIN D2; 24 HYDROXYERGOCALCIFEROL; ALFACALCIDOL; ALPHA NAPHTHOFLAVONE; COLECALCIFEROL HYDROXYLASE; CYTOCHROME B5; CYTOCHROME P450 1A1; CYTOCHROME P450 1A2; CYTOCHROME P450 1B1; CYTOCHROME P450 2A6; CYTOCHROME P450 2B6; CYTOCHROME P450 2C18; CYTOCHROME P450 2C19; CYTOCHROME P450 2C8; CYTOCHROME P450 2C9; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; CYTOCHROME P450 4A11; CYTOCHROME P450 ISOENZYME; DOXERCALCIFEROL; ERGOCALCIFEROL; ISONIAZID; KETOCONAZOLE; OXYGENASE; TACALCITOL; TESTOSTERONE; TROLEANDOMYCIN; UNCLASSIFIED DRUG; VITAMIN D; VITAMIN D 24 HYDROXYLASE;

ARTICLE; BACULOVIRUS; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME STRUCTURE; ESCHERICHIA COLI; GAS CHROMATOGRAPHY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; HYDROXYLATION; INSECT CELL; LIVER MICROSOME; MASS SPECTROMETRY; NONHUMAN; PRIORITY JOURNAL; SITE DIRECTED MUTAGENESIS; STRUCTURE ANALYSIS; VITAMIN D METABOLISM;

ANIMALS; BACULOVIRIDAE; CYTOCHROME P-450 CYP27A1; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; INSECTS; ISONIAZID; KETOCONAZOLE; KINETICS; MICROSOMES, LIVER; MUTAGENESIS, SITE-DIRECTED; RECOMBINANT PROTEINS; STEROID HYDROXYLASES; TRANSFECTION; TROLEANDOMYCIN; VITAMIN D;

ESCHERICHIA COLI; INSECTA; UNIDENTIFIED BACULOVIRUS;

EID: 14044271607     PISSN: 0021972X     EISSN: None     Source Type: Journal    
DOI: 10.1210/jc.2004-0966     Document Type: Article

References (43)

1. Gillespie WJ, Avencil A, Henry DA, O'Connell DL, Robertson J 2001 Vitamin D and vitamin D analogs for preventing fractures associated with involutional and postmenopausal osteoporosis. Cochrane Database Syst Rev 2:CD000227
2. Brown AJ 2001 Therapeutic uses of vitamin D analogues. Am J Kidney Dis 38(Suppl 5):S3-S19
3. Bell NH 2001 Osteomalacia and rickets. In: Becker KL, Bilezikian JP, Bremner WJ, Willington H, Kahn CR, Loriaux DL, Nylen ES, Rebar RW, Robertson GL, Snider Jr RH, Wartofsky L, eds. Principles and practice of endocrinology and metabolism. 3rd ed. Philadelphia: Lippincott Williams, Wilkins; 615-623
4. 2 in mammals. Biochemistry 29:578-582
5. 2 made in the human hepatoma, Hep3B. Biochem J 310:233-241
6. 2 detectable in human serum. J Clin Endocrinol Metab 83:2156-2165
7. Guo Y-D, Strugnell S, Back DW, Jones G 1993 Transfected human liver cytochrome P-450 hydroxylates vitamin D analogs at different side-chain positions. Proc Natl Acad Sci USA 90:8668-8672
8. 3 25 hydroxylase (CYP2D25). Catalytic properties, tissue distribution, and comparison with human CYP2D6. J Biol Chem 275:34650-34655
9. Gupta RP, Hollis BW, Patel SP, Patrick KS, Bell NH 2004 CYP3A4 is a human microsomal vitamin D-25-hydroxylase. J Bone Miner Res 19:680-688
10. Human liver microsome assays. http//www:gentest.com/products/tissue_frac/ prod_inserts/hlm_meth.shtml. Accessed 5/23/02.
11. Harlow GR, Halpert JR 1997 Alanine-screening mutagenesis of a putative substrate recognition site in human cytochrome P450 3A4: role of residues 210 and 211 in flavanoid activation and substrate specificity. J Biol Chem 272:5396-5402
12. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzaon MD, Fujimoto IK, Goeke NM, Olson BJ, Klenk DC 1985 Measurement of protein using bicinchoninic acid. Anal Biochem 150:76-85
13. Khan KK, Halpert JR 2000 Structure-function analysis of human cytochrome P450 3A4 using 7-alkoxycoumarins as active-site probes. Arch Biochem Biophys 373:335-345
14. He YA, Roussel F, Halpert JR 2002 Analysis of homotropic and heterotropic cooperativity of diazepam oxidation by CYP3A4 using site-directed mutagenesis and kinetic modeling. Arch Biochem Biophys 409:92-101
15. Khan KK, He YQ, Domanski TL, Halpert JR 2002 Midazolam oxidation by cytochrome P450 3A4 and active-site mutants: an evaluation of multiple binding sites and of the metabolic pathway that leads to enzyme inactivation. Mol Pharmacol 61:495-506
16. Eiselt R, Domanski TL, Zibat A, Mueller R, Presecan-Siedel E, Hustert E, Zanger UM, Brockmoller J, Klenk HP, Meyer UA, Khan KK, He YA, Halpert JR, Wojnowski L 2001 Identification and functional characterization of eight CYP3A4 protein variants. Pharmacogenetics 11:447-458
17. Domanski TL, He YA, Khan KK, Roussel F, Wang Q, Halpert JR 2001 Phenylalanine and tryptophan scanning mutagenesis of CYP3A4 substrate recognition site residue and the effect on substrate oxidation and cooperativity. Biochemistry 40:10150-10160
18. Hollis BW 1997 Detection of vitamin D and its major metabolites. In: Feldman DD, Glorieux FH, Pike JW, eds. Vitamin D. San Diego: Academic Press; 587-606
19. 125I-labeled tracer. Clin Chem 39:529-533
20. 3 metabolism. Methods Enzymol 123:141-154
21. Roy P, Yu LJ, Crespi CL, Waxman DJ 1999 Development of a substrate-activity-based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos 27:655-666
22. Ono S, Hatanaka T, Hotta H, Satoh T, Gonzalez FJ, Tsutsui M1996 Specificity of substrate and inhibitor probes for cytochrome P450s: evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes. Xenobiotica 26:681-693
23. Desta Z, Soukhova NV, Flockhart DA 2001 Inhibition of cytochrome P450 (CYP450) isoforms by isoniazid: potent inhibition of CYP2C19 and CYP3A. Antimicrob Agents Chemother 45:382-392
24. Ghosal A, Satoh H, Thomas PE, Bush E, Moore D 1996 Inhibition and kinetics of cytochrome P4503A activity in microsomes from rat, human, and cDNA-expressed human cytochrome P450. Drug Metab Dispos 24:940-947
25. Ueng Y-F, Kuwabara T, Chun Y-J, Guengerich FP 1997 Cooperativity in oxidations catalyzed by cytochrome P450 3A4. Biochemistry 36:370-381
26. Sai Y, Dai R, Yang TJ, Krausz KW, Gonzalez FJ, Gelboin HV, Shou M 2000 Assessment of specificity of eight chemical inhibitors using cDNA-expressed cytochromes P450. Xenobiotica 30:327-343
27. Hashimoto H, Toide K, Kitamura R, Fujita M, Tagawa S, Itoh S, Kamataki T 1993 Gene structure of CYP3A4, an adult-specific form of cytochrome P450 in human livers, and its transcriptional control. Eur J Biochem 218:585-595
28. Schuetz JD, Beach DL, Guzelian PS 1994 Selective expression of cytochrome P450 CYP3A mRNAs in embryonic and adult human liver. Pharmacogenetics 4:11-20
29. Zhang CY, Dunbar D, Ostrowska A, Zeisloft S, Yang J, Kaminsky LS 1999 Characterization of human small intestinal cytochromes P-450. Drug Metab Dispos 27:804-809
30. Andersen MR, Farin FM, Omiecinski CJ 1998 Quantification of multiple human cytochrome P450 mRNA molecules using competitive reverse transcriptase-PCR. DNA Cell Biol 17:231-238
31. Edwards RJ, Adams DA, Watts PS, Davies DS, Boobis AR 1998 Development of a comprehensive panel of antibodies against the major xenobiotic metabolizing forms of cytochrome P450 in humans. Biochem Pharmacol 56:177-187
32. Stiborova M, Martinek V, Rydlova H, Hodek P, Frei E 2002 Sudan I is a potential carcinogen for humans: evidence for its metabolic activation and detoxication by human recombinant cytochrome P450 1A1 and liver microsomes. Cancer Res 62:5678-5684
33. de Wildt SN, Kearns GL, Leeder JS, van den Anker JN 1999 Cytochrome P450 3A: ontogeny and drug disposition. Clin Pharmacokinet 37:485-506
34. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich P 1994 Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals; studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414-423
35. Westlind A, Löfberg L, Tindberg N, Andersson TB, Ingel-Sundberg M 1999 Interindividual differences in hepatic expression of CYP3A4: relationship to genetic polymorphism in the 5′-upstream regulatory region. Biochem Biophys Res Commun 259:201-205
36. 3, calcitriol, and calcipotriol. Biochem Pharmacol 55:829-837
37. 3] on selected vitamin D-regulated events in the rat. Biochem Pharmacol 60:701-708
38. 2 on calcium homeostasis in postmenopausal osteopenic women. J Bone Miner Res 9:607-614
39. 2 in hemodialysis patients with moderate to severe secondary hyperparathyroidism. Kidney Int 51:583-630
40. 5. Arch Biochem Biophys 348:107-115
41. Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW 2003 Deorphanization of cytochrome P450 CYP2R1, a microsomal vitamin D 25-hydroxylase. J Biol Chem 278:38084-38093
42. Casella SJ, Reiner BJ, Chen TC, Holick MF, Harrison HE 1994 A possible genetic defect in 25-hydroxylation as a cause of rickets. J Pediatr 124:929-932
43. Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW 2004 Genetic evidence that human CYP2R1 is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci USA 101:711-715