25-Hydroxyvitamin D 1-alpha-hydroxylase explained

calcidiol 1-monooxygenase
Ec Number:	1.14.15.18
Cas Number:	9081-36-1
Go Code:	0004498

25-Hydroxyvitamin D 1-alpha-hydroxylase (VD 1A hydroxylase) also known as calcidiol 1-monooxygenase ^[1] or cytochrome p450 27B1 (CYP27B1) or simply 1-alpha-hydroxylase is a cytochrome P450 enzyme that in humans is encoded by the CYP27B1 gene.^{[2] [3] [4]}

VD 1A hydroxylase is located in the proximal tubule of the kidney and a variety of other tissues, including skin (keratinocytes), immune cells,^[5] and bone (osteoblasts).^[6]

Reactions

The enzyme catalyzes the hydroxylation of calcifediol to calcitriol (the bioactive form of Vitamin D):^[7]

calcidiol + 2 reduced adrenodoxin + 2 H⁺ + O₂ calcitriol + 2 oxidized adrenodoxin + H₂O

The enzyme is also able to oxidize ercalcidiol (25-OH D2) to ercalcitriol, secalciferol to calcitetrol, and 25-hydroxy-24-oxocalciol to (1S)-1,25-dihydroxy-24-oxocalciol.^[8]

Clinical significance

Loss-of-function mutations in CYP27B1 cause Vitamin D-dependent rickets, type IA.^[9]

Further reading

• Carr EJ, Niederer HA, Williams J, Harper L, Watts RA, Lyons PA, Smith KG . Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis . BMC Medical Genetics . 10 . 121 . 2009 . 19951419 . 3224698 . 10.1186/1471-2350-10-121 . free .
• Alzahrani AS, Zou M, Baitei EY, Alshaikh OM, Al-Rijjal RA, Meyer BF, Shi Y . A novel G102E mutation of CYP27B1 in a large family with vitamin D-dependent rickets type 1 . The Journal of Clinical Endocrinology and Metabolism . 95 . 9 . 4176–83 . Sep 2010 . 20534770 . 10.1210/jc.2009-2278 . free .
• Lagishetty V, Chun RF, Liu NQ, Lisse TS, Adams JS, Hewison M . 1alpha-hydroxylase and innate immune responses to 25-hydroxyvitamin D in colonic cell lines . The Journal of Steroid Biochemistry and Molecular Biology . 121 . 1–2 . 228–33 . Jul 2010 . 20152900 . 2891066 . 10.1016/j.jsbmb.2010.02.004 .
• Giroux S, Elfassihi L, Clément V, Bussières J, Bureau A, Cole DE, Rousseau F . High-density polymorphisms analysis of 23 candidate genes for association with bone mineral density . Bone . 47 . 5 . 975–81 . Nov 2010 . 20654748 . 10.1016/j.bone.2010.06.030 .
• Zhou S, LeBoff MS, Glowacki J . Vitamin D metabolism and action in human bone marrow stromal cells . Endocrinology . 151 . 1 . 14–22 . Jan 2010 . 19966181 . 2803155 . 10.1210/en.2009-0969 .
• Payne AH, Hales DB . Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones . Endocrine Reviews . 25 . 6 . 947–70 . Dec 2004 . 15583024 . 10.1210/er.2003-0030 . free .
• Maver A, Medica I, Salobir B, Tercelj M, Peterlin B . Lack of association of immune-response-gene polymorphisms with susceptibility to sarcoidosis in Slovenian patients . Genetics and Molecular Research . 9 . 1 . 58–68 . 2010 . 20082271 . 10.4238/vol9-1gmr682 . free .
• Shen H, Bielak LF, Ferguson JF, Streeten EA, Yerges-Armstrong LM, Liu J, Post W, O'Connell JR, Hixson JE, Kardia SL, Sun YV, Jhun MA, Wang X, Mehta NN, Li M, Koller DL, Hakonarson H, Keating BJ, Rader DJ, Shuldiner AR, Peyser PA, Reilly MP, Mitchell BD . Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification . Arteriosclerosis, Thrombosis, and Vascular Biology . 30 . 12 . 2648–54 . Dec 2010 . 20847308 . 2988112 . 10.1161/ATVBAHA.110.211805 .
• Sundqvist E, Bäärnhielm M, Alfredsson L, Hillert J, Olsson T, Kockum I . Confirmation of association between multiple sclerosis and CYP27B1 . European Journal of Human Genetics . 18 . 12 . 1349–52 . Dec 2010 . 20648053 . 3002863 . 10.1038/ejhg.2010.113 .
• Fichna M, Zurawek M, Januszkiewicz-Lewandowska D, Gryczyñska M, Fichna P, Sowiñski J, Nowak J . Association of the CYP27B1 C(-1260)A polymorphism with autoimmune Addison's disease . Experimental and Clinical Endocrinology & Diabetes . 118 . 8 . 544–9 . Aug 2010 . 19998245 . 10.1055/s-0029-1241206 . 5609583 .
• Holt SK, Kwon EM, Koopmeiners JS, Lin DW, Feng Z, Ostrander EA, Peters U, Stanford JL . Vitamin D pathway gene variants and prostate cancer prognosis . The Prostate . 70 . 13 . 1448–60 . Sep 2010 . 20687218 . 2927712 . 10.1002/pros.21180 .
• Bu FX, Armas L, Lappe J, Zhou Y, Gao G, Wang HW, Recker R, Zhao LJ . 5782938 . Comprehensive association analysis of nine candidate genes with serum 25-hydroxy vitamin D levels among healthy Caucasian subjects . Human Genetics . 128 . 5 . 549–56 . Nov 2010 . 20809279 . 10.1007/s00439-010-0881-9 .
• Fichna M, Zurawek M, Januszkiewicz-Lewandowska D, Fichna P, Nowak J . PTPN22, PDCD1 and CYP27B1 polymorphisms and susceptibility to type 1 diabetes in Polish patients . International Journal of Immunogenetics . 37 . 5 . 367–72 . Oct 2010 . 20518841 . 10.1111/j.1744-313X.2010.00935.x . 19398299 .
• Wjst M, Heimbeck I, Kutschke D, Pukelsheim K . 29338132 . Epigenetic regulation of vitamin D converting enzymes . The Journal of Steroid Biochemistry and Molecular Biology . 121 . 1–2 . 80–3 . Jul 2010 . 20304056 . 10.1016/j.jsbmb.2010.03.056 .
• Liu CY, Wu MC, Chen F, Ter-Minassian M, Asomaning K, Zhai R, Wang Z, Su L, Heist RS, Kulke MH, Lin X, Liu G, Christiani DC . A Large-scale genetic association study of esophageal adenocarcinoma risk . Carcinogenesis . 31 . 7 . 1259–63 . Jul 2010 . 20453000 . 2893800 . 10.1093/carcin/bgq092 .
• Sunyer J, Basagaña X, González JR, Júlvez J, Guerra S, Bustamante M, de Cid R, Antó JM, Torrent M . Early life environment, neurodevelopment and the interrelation with atopy . Environmental Research . 110 . 7 . 733–8 . Oct 2010 . 20701904 . 10.1016/j.envres.2010.07.005 . 2010ER....110..733S .
• Simon KC, Munger KL, Ascherio A . Polymorphisms in vitamin D metabolism related genes and risk of multiple sclerosis . Multiple Sclerosis (Houndmills, Basingstoke, England) . 16 . 2 . 133–8 . Feb 2010 . 20007432 . 2819633 . 10.1177/1352458509355069 .
• Hendrickson SL, Lautenberger JA, Chinn LW, Malasky M, Sezgin E, Kingsley LA, Goedert JJ, Kirk GD, Gomperts ED, Buchbinder SP, Troyer JL, O'Brien SJ . Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression . PLOS ONE . 5 . 9 . e12862 . 2010 . 20877624 . 2943476 . 10.1371/journal.pone.0012862 . 2010PLoSO...512862H . Badger . Jonathan H. . free .
• Dusso AS, Brown AJ, Slatopolsky E . Vitamin D . American Journal of Physiology. Renal Physiology . 289 . 1 . F8–28 . Jul 2005 . 15951480 . 10.1152/ajprenal.00336.2004 .
• Bailey SD, Xie C, Do R, Montpetit A, Diaz R, Mohan V, Keavney B, Yusuf S, Gerstein HC, Engert JC, Anand S . Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study . Diabetes Care . 33 . 10 . 2250–3 . Oct 2010 . 20628086 . 2945168 . 10.2337/dc10-0452 .

Notes and References

1. Web site: 25-Hydroxyvitamin D3 1-Alpha-Hydroxylase - an overview | ScienceDirect Topics .
2. Web site: Entrez Gene: cytochrome P450.
3. Takeyama K, Kitanaka S, Sato T, Kobori M, Yanagisawa J, Kato S . 25-Hydroxyvitamin D3 1alpha-hydroxylase and vitamin D synthesis . Science . 277 . 5333 . 1827–30 . Sep 1997 . 9295274 . 10.1126/science.277.5333.1827 .
4. Monkawa T, Yoshida T, Wakino S, Shinki T, Anazawa H, Deluca HF, Suda T, Hayashi M, Saruta T . Molecular cloning of cDNA and genomic DNA for human 25-hydroxyvitamin D3 1 alpha-hydroxylase . Biochemical and Biophysical Research Communications . 239 . 2 . 527–33 . Oct 1997 . 9344864 . 10.1006/bbrc.1997.7508 .
5. Sigmundsdottir H, Pan J, Debes GF, Alt C, Habtezion A, Soler D, Butcher EC . 9540123 . DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27 . Nature Immunology . 8 . 3 . 285–93 . Mar 2007 . 17259988 . 10.1038/ni1433 .
6. Kogawa M, Findlay DM, Anderson PH, Ormsby R, Vincent C, Morris HA, Atkins GJ . Osteoclastic metabolism of 25(OH)-vitamin D3: a potential mechanism for optimization of bone resorption . Endocrinology . 151 . 10 . 4613–25 . Oct 2010 . 20739402 . 10.1210/en.2010-0334 . free .
7. Gray RW, Omdahl JL, Ghazarian JG, DeLuca HF . 25-Hydroxycholecalciferol-1-hydroxylase. Subcellular location and properties . The Journal of Biological Chemistry . 247 . 23 . 7528–32 . Dec 1972 . 10.1016/S0021-9258(19)44557-2 . 4404596 . free .
8. Sawada . N . Sakaki . T . Kitanaka . S . Takeyama . K . Kato . S . Inouye . K . Enzymatic properties of human 25-hydroxyvitamin D3 1alpha-hydroxylase coexpression with adrenodoxin and NADPH-adrenodoxin reductase in Escherichia coli. . European Journal of Biochemistry . November 1999 . 265 . 3 . 950–6 . 10.1046/j.1432-1327.1999.00794.x . 10518789. free .
9. Web site: # 264700 - VITAMIN D HYDROXYLATION-DEFICIENT RICKETS, TYPE 1A; VDDR1A . www.omim.org . en-us.