CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo

Proceedings of the National Academy of Sciences of the United States of America

Volumn 110, Issue 39, 2013, Pages 15650-15655

  Zhu, Jinge G ^a   Ochalek, Justin T ^a   Kaufmann, Martin ^b   Jones, Glenville ^b   DeLuca, Hector F ^a  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

^b QUEEN S UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

1ALPHA,25 DIHYDROXYVITASTRONGLY D3; 25 HYDROXYVITAMIN D; CALCIFEDIOL; CYP2R1 ENZYME; CYTOCHROME; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; EMBRYONIC STEM CELL; ENDOCRINE SYSTEM; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROXYLATION; IN VIVO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; REAL TIME POLYMERASE CHAIN REACTION; SEXUAL MATURITY; WILD TYPE;

ANIMALS; CALCIUM; CHOLESTANETRIOL 26-MONOOXYGENASE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; EPIPHYSES; FEMALE; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENES, REPORTER; GENOME; LUCIFERASES; MASS SPECTROMETRY; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; PHOSPHORUS; RADIOIMMUNOASSAY; REAL-TIME POLYMERASE CHAIN REACTION; RNA, MESSENGER; VITAMIN D;

EID: 84884597662     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1315006110     Document Type: Article

References (64)

1. Holick MF (2011) Vitamin D: Evolutionary, physiological and health perspectives. Curr Drug Targets 12(1):4-18.
2. Christakos S, DeLuca HF (2011) Minireview: Vitamin D: Is there a role in extraskeletal health? Endocrinology 152 8 2930-2930.
3. Rosen CJ, et al. (2012) The nonskeletal effects of vitamin D: An Endocrine Society scientific statement. Endocr Rev 33(3):456-492.
4. Zhu J, DeLuca HF (2012) Vitamin D 25-hydroxylase-Four decades of searching, are we there yet? Arch Biochem Biophys 523 (1) :30-36.
5. Henry HL (2005) The 25-hydroxyvitamin D 1?-hydroxylase. Vitamin D, eds Feldman D, Pike JW, Glorieux FH (Elsevier Academic Press, San Diego, CA), 2nd Ed, Vol 1, pp 69-83.
6. Norlin M, Wikvall K (2007) Enzymes in the conversion of cholesterol into bile acids. Curr Mol Med 7(2):199-218.
7. Lorbek G, LewinskaM, Rozman D (2012) Cytochrome P450s in the synthesis of cholesterol and bile acids-from mouse models to human diseases. FEBS J 279(9):1516-1533.
8. Cali JJ, Russell DW (1991) Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis. J Biol Chem 266(12):7774-7778.
9. Guo YD, 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(18):8668-8672.
10. Akiyoshi-Shibata M, et al. (1991) Expression of rat liver vitamin D3 25-hydroxylase cDNA in Saccharomyces cerevisiae. FEBS Lett 280(2):367-370.
11. Axén E, Postlind H, Sjöberg H, Wikvall K (1994) Liver mitochondrial cytochrome P450 CYP27 and recombinant-expressed human CYP27 catalyze 1 alpha-hydroxylation of 25-hydroxyvitamin D3. Proc Natl Acad Sci USA 91(21):10014-10018.
12. Pikuleva IA, Björkhem I, Waterman MR (1997) Expression, purification, and enzymatic properties of recombinant human cytochrome P450c27 (CYP27). Arch Biochem Biophys 343(1):123-130.
13. Sawada N, Sakaki T, Ohta M, Inouye K (2000) Metabolism of vitamin D(3) by human CYP27A1. Biochem Biophys Res Commun 273(3):977-984.
14. Araya Z, Hosseinpour F, Bodin K, Wikvall K (2003) Metabolism of 25-hydroxyvitamin D3 by microsomal and mitochondrial vitamin D3 25-hydroxylases (CYP2D25 and CYP27A1): A novel reaction by CYP27A1. Biochim Biophys Acta 1632(1-3):40-47.
15. Rosen H, et al. (1998) Markedly reduced bile acid synthesis but maintained levels of cholesterol and vitamin D metabolites in mice with disrupted sterol 27-hydroxylase gene. J Biol Chem 273(24):14805-14812.
16. Repa JJ, et al. (2000) Disruption of the sterol 27-hydroxylase gene in mice results in hepatomegaly and hypertriglyceridemia. Reversal by cholic acid feeding. J Biol Chem 275(50):39685-39692.
17. Moghadasian MH (2004) Cerebrotendinous xanthomatosis: Clinical course, genotypes and metabolic backgrounds. Clin Invest Med 27(1):42-50.
18. Gallus GN, Dotti MT, Federico A (2006) Clinical and molecular diagnosis of cerebrotendinous xanthomatosis with a review of the mutations in the CYP27A1 gene. Neurol Sci 27(2):143-149.
19. Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW (2003) De-orphanization of cytochrome P450 2R1: A microsomal vitamin D 25-hydroxilase. J Biol Chem 278(39): 38084-38093.
20. Shinkyo R, Sakaki T, Kamakura M, Ohta M, Inouye K (2004) Metabolism of vitamin D by human microsomal CYP2R1. Biochem Biophys Res Commun 324(1):451-457.
21. Strushkevich N, Usanov SA, Plotnikov AN, Jones G, Park HW (2008) Structural analysis of CYP2R1 in complex with vitamin D3. J Mol Biol 380(1):95-106.
22. 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(6):929-932.
23. Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW (2004) Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci USA 101(20):7711-7715.
24. Dong Q, Miller WL (2004) Vitamin D 25-hydroxylase deficiency. Mol Genet Metab 83(1-2):197-198.
25. Levine MA, et al. (2007) Tropical rickets in Nigeria: Mutation of the CYP2R1 gene encoding vitamin D 25-hydroxylase as a cause of vitamin D dependent rickets. Bone 40:S60-S61.
26. Al Mutair AN, Nasrat GH, Russell DW (2012) Mutation of the CYP2R1 vitamin D 25-hydroxylase in a Saudi Arabian family with severe vitamin D deficiency. J Clin Endocrinol Metab 97(10):E2022-E2025.
27. Arbour NC, Ross TK, Zierold C, Prahl JM, DeLuca HF (1998) A highly sensitive method for large-scale measurements of 1,25-dihydroxyvitamin D. Anal Biochem 255(1): 148-154.
28. Tanaka Y, Deluca HF (1974) Role of 1,25-dihydroxyvitamin D3 in maintaining serum phosphorus and curing rickets. Proc Natl Acad Sci USA 71(4):1040-1044.
29. Choudhary D, Jansson I, Stoilov I, Sarfarazi M, Schenkman JB (2005) Expression patterns of mouse and human CYP orthologs (families 1-4) during development and in different adult tissues. Arch Biochem Biophys 436(1):50-61.
30. Nelson DR (2003) Comparison of P450s from human and fugu: 420 million years of vertebrate P450 evolution. Arch Biochem Biophys 409(1):18-24.
31. Yamasaki T, Izumi S, Ide H, Ohyama Y (2004) Identification of a novel rat microsomal vitamin D3 25-hydroxylase. J Biol Chem 279(22):22848-22856.
32. Bièche I, et al. (2007) Reverse transcriptase-PCR quantification of mRNA levels from cytochrome (CYP)1, CYP2 and CYP3 families in 22 different human tissues. Pharmacogenet Genomics 17(9):731-742.
33. Foresta C, et al. (2011) Bone mineral density and testicular failure: Evidence for a role of vitamin D 25-hydroxylase in human testis. J Clin Endocrinol Metab 96(4): E646-E652.
34. Blomberg Jensen M, et al. (2010) Vitamin D receptor and vitamin D metabolizing enzymes are expressed in the human male reproductive tract. Hum Reprod 25(5): 1303-1311.
35. Foresta C, et al. (2013) Altered bone status in unilateral testicular cancer survivors: Role of CYP2R1 and its luteinizing hormone-dependency. J Endocrinol Invest 36(6): 379-384.
36. Ahn J, et al. (2010) Genome-wide association study of circulating vitamin D levels. Hum Mol Genet 19(13):2739-2745.
37. Wang TJ, et al. (2010) Common genetic determinants of vitamin D insufficiency: A genome-wide association study. Lancet 376(9736):180-188.
38. Zhu H, et al. (2013) A genome-wide methylation study of severe vitamin D deficiency in African American adolescents. J Pediatr 162(5):1004-1009.e1.
39. Ramos-Lopez E, Brück P, Jansen T, Herwig J, Badenhoop K (2007) CYP2R1 (vitamin D 25-hydroxylase) gene is associated with susceptibility to type 1 diabetes and vitamin D levels in Germans. Diabetes Metab Res Rev 23(8):631-636.
40. Cooper JD, et al. (2011) Inherited variation in vitamin D genes is associated with predisposition to autoimmune disease type 1 diabetes. Diabetes 60(5):1624-1631.
41. Hussein AG, Mohamed RH, Alghobashy AA (2012) Synergism of CYP2R1 and CYP27B1 polymorphisms and susceptibility to type 1 diabetes in Egyptian children. Cell Immunol 279(1):42-45.
42. Simon KC, et al. (2011) Genetic predictors of 25-hydroxyvitamin D levels and risk of multiple sclerosis. J Neurol 258(9):1676-1682.
43. Andersson S, Davis DL, Dahlbäck H, Jörnvall H, Russell DW (1989) Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J Biol Chem 264(14):8222-8229.
44. Usui E, Noshiro M, Okuda K (1990) Molecular cloning of cDNA for vitamin D3 25-hydroxylase from rat liver mitochondria. FEBS Lett 262(1):135-138.
45. Su P, et al. (1990) A cDNA encoding a rat mitochondrial cytochrome P450 catalyzing both the 26-hydroxylation of cholesterol and 25-hydroxylation of vitamin D3: Gonadotropic regulation of the cognate mRNA in ovaries. DNA Cell Biol 9(9):657-667.
46. Thummel KE, et al. (2001) Transcriptional control of intestinal cytochrome P-4503A by 1alpha,25-dihydroxy vitamin D3. Mol Pharmacol 60(6):1399-1406.
47. Drocourt L, Ourlin JC, Pascussi JM, Maurel P, Vilarem MJ (2002) Expression of CYP3A4, CYP2B6, and CYP2C9 is regulated by the vitamin D receptor pathway in primary human hepatocytes. J Biol Chem 277(28):25125-25132.
48. Thompson PD, et al. (2002) Liganded VDR induces CYP3A4 in small intestinal and colon cancer cells via DR3 and ER6 vitamin D responsive elements. Biochem Biophys Res Commun 299(5):730-738.
49. Jurutka PW, et al. (2005) Molecular and functional comparison of 1,25-dihydroxyvitamin D(3) and the novel vitamin D receptor ligand, lithocholic acid, in activating transcription of cytochrome P450 3A4. J Cell Biochem 94(5):917-943.
50. Pavek P, et al. (2010) Intestinal cell-specific vitamin D receptor (VDR)-mediated transcriptional regulation of CYP3A4 gene. Biochem Pharmacol 79(2):277-287.
51. Wang Y, Zhu J, DeLuca HF (2012) Where is the vitamin D receptor? Arch Biochem Biophys 523 (1):123-133.
52. Gupta RP, Hollis BW, Patel SB, Patrick KS, Bell NH (2004) CYP3A4 is a human microsomal vitamin D 25-hydroxylase. J Bone Miner Res 19(4):680-688.
53. Gupta RP, He YA, Patrick KS, Halpert JR, Bell NH (2005) CYP3A4 is a vitamin D-24-and 25-hydroxylase: Analysis of structure function by site-directed mutagenesis. J Clin Endocrinol Metab 90(2):1210-1219.
54. Wu S, et al. (1997) Molecular cloning, expression, and functional significance of a cytochrome P450 highly expressed in rat heart myocytes. J Biol Chem 272(19): 12551-12559.
55. Spiecker M, Liao J (2006) Cytochrome P450 epoxygenase CYP2J2 and the risk of coronary artery disease. Trends Cardiovasc Med 16(6):204-208.
56. Thelen K, Dressman JB (2009) Cytochrome P450-mediated metabolism in the human gut wall. J Pharm Pharmacol 61(5):541-558.
57. Aiba I, et al. (2006) Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases. Steroids 71(10):849-856.
58. Itaya K, Ui M (1966) A new micromethod for the colorimetric determination of inorganic phosphate. Clin Chim Acta 14(3):361-366.
59. Higashi T, Awada D, Shimada K (2001) Simultaneous determination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in human plasma by liquid chromatographytandem mass spectrometry employing derivatization with a Cookson-type reagent. Biol Pharm Bull 24(7):738-743.
60. Vanhooke JL, et al. (2006) CYP27B1 null mice with LacZreporter gene display no 25-hydroxyvitamin D3-1alpha-hydroxylase promoter activity in the skin. Proc Natl Acad Sci USA 103(1):75-80.
61. Amling M, et al. (1999) Rescue of the skeletal phenotype of vitamin D receptor-ablated mice in the setting of normal mineral ion homeostasis: Formal histomorphometric and biomechanical analyses. Endocrinology 140(11):4982-4987.
62. Neville PF, DeLuca HF (1966) The synthesis of [1,2-3H]vitamin D3 and the tissue localization of a 0.25-mu-g (10 IU) dose per rat. Biochemistry 5(7):2201-2207.
63. Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37(8):911-917.
64. Yang S, Smith C, Prahl JM, Luo X, DeLuca HF (1993) Vitamin D deficiency suppresses cell-mediated immunity in vivo. Arch Biochem Biophys 303(1):98-106.