25-Hydroxyvitamin D 1-alpha-hydroxylase
| calcidiol 1-monooxygenase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 1.14.15.18 | ||||||||
| CAS no. | 9081-36-1 | ||||||||
| Databases | |||||||||
| BRENDA | enzyme data | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | enzyme entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| Rhea | reactions | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
25-Hydroxyvitamin D 1-alpha-hydroxylase (VD 1A hydroxylase) also known as calcidiol 1-monooxygenase or cytochrome p450 27B1 (CYP27B1) or simply 1-alpha-hydroxylase is a cytochrome P450 enzyme that in humans is encoded by the CYP27B1 gene.
VD 1A hydroxylase is located in the proximal tubule of the kidney and a variety of other tissues, including skin (keratinocytes), immune cells, and bone (osteoblasts).
Reactions
The enzyme catalyzes the hydroxylation of calcifediol to calcitriol (the bioactive form of Vitamin D):
- 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.
Clinical significance
Loss-of-function mutations in CYP27B1 cause Vitamin D-dependent rickets, type IA.
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.
- ↑ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".
References
- 1 2 3 GRCh38: Ensembl release 89: ENSG00000111012 – Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000006724 – Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ Enzyme 1.14.15.18 at KEGG Pathway Database.
- ↑ "Entrez Gene: cytochrome P450".
- ↑ Takeyama K, Kitanaka S, Sato T, Kobori M, Yanagisawa J, Kato S (Sep 1997). "25-Hydroxyvitamin D3 1alpha-hydroxylase and vitamin D synthesis". Science. 277 (5333). New York, N.Y.: 1827–1830. doi:10.1126/science.277.5333.1827. PMID 9295274.
- ↑ Monkawa T, Yoshida T, Wakino S, Shinki T, Anazawa H, Deluca HF, et al. (Oct 1997). "Molecular cloning of cDNA and genomic DNA for human 25-hydroxyvitamin D3 1 alpha-hydroxylase". Biochemical and Biophysical Research Communications. 239 (2): 527–533. doi:10.1006/bbrc.1997.7508. PMID 9344864.
- ↑ Sigmundsdottir H, Pan J, Debes GF, Alt C, Habtezion A, Soler D, et al. (Mar 2007). "DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27". Nature Immunology. 8 (3): 285–293. doi:10.1038/ni1433. PMID 17259988.
- ↑ Kogawa M, Findlay DM, Anderson PH, Ormsby R, Vincent C, Morris HA, et al. (Oct 2010). "Osteoclastic metabolism of 25(OH)-vitamin D3: a potential mechanism for optimization of bone resorption". Endocrinology. 151 (10): 4613–4625. doi:10.1210/en.2010-0334. PMID 20739402.
- ↑ Gray RW, Omdahl JL, Ghazarian JG, DeLuca HF (Dec 1972). "25-Hydroxycholecalciferol-1-hydroxylase. Subcellular location and properties". The Journal of Biological Chemistry. 247 (23): 7528–7532. doi:10.1016/S0021-9258(19)44557-2. PMID 4404596.
- ↑ Sawada N, Sakaki T, Kitanaka S, Takeyama K, Kato S, Inouye K (November 1999). "Enzymatic properties of human 25-hydroxyvitamin D3 1alpha-hydroxylase coexpression with adrenodoxin and NADPH-adrenodoxin reductase in Escherichia coli". European Journal of Biochemistry. 265 (3): 950–956. doi:10.1046/j.1432-1327.1999.00794.x. PMID 10518789.
- ↑ Online Mendelian Inheritance in Man (OMIM): VITAMIN D HYDROXYLATION-DEFICIENT RICKETS, TYPE 1A; VDDR1A - 264700
Further reading
- Carr EJ, Niederer HA, Williams J, Harper L, Watts RA, Lyons PA, et al. (Dec 2009). "Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis". BMC Medical Genetics. 10 121. doi:10.1186/1471-2350-10-121. PMC 3224698. PMID 19951419.
- Alzahrani AS, Zou M, Baitei EY, Alshaikh OM, Al-Rijjal RA, Meyer BF, et al. (Sep 2010). "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): 4176–4183. doi:10.1210/jc.2009-2278. PMID 20534770.
- Lagishetty V, Chun RF, Liu NQ, Lisse TS, Adams JS, Hewison M (Jul 2010). "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): 228–233. doi:10.1016/j.jsbmb.2010.02.004. PMC 2891066. PMID 20152900.
- Giroux S, Elfassihi L, Clément V, Bussières J, Bureau A, Cole DE, et al. (Nov 2010). "High-density polymorphisms analysis of 23 candidate genes for association with bone mineral density". Bone. 47 (5): 975–981. doi:10.1016/j.bone.2010.06.030. PMID 20654748.
- Zhou S, LeBoff MS, Glowacki J (Jan 2010). "Vitamin D metabolism and action in human bone marrow stromal cells". Endocrinology. 151 (1): 14–22. doi:10.1210/en.2009-0969. PMC 2803155. PMID 19966181.
- Payne AH, Hales DB (Dec 2004). "Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones". Endocrine Reviews. 25 (6): 947–970. doi:10.1210/er.2003-0030. PMID 15583024.
- Maver A, Medica I, Salobir B, Tercelj M, Peterlin B (Jan 2010). "Lack of association of immune-response-gene polymorphisms with susceptibility to sarcoidosis in Slovenian patients". Genetics and Molecular Research. 9 (1): 58–68. doi:10.4238/vol9-1gmr682. PMID 20082271.
- Shen H, Bielak LF, Ferguson JF, Streeten EA, Yerges-Armstrong LM, Liu J, et al. (Dec 2010). "Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification". Arteriosclerosis, Thrombosis, and Vascular Biology. 30 (12): 2648–2654. doi:10.1161/ATVBAHA.110.211805. PMC 2988112. PMID 20847308.
- Sundqvist E, Bäärnhielm M, Alfredsson L, Hillert J, Olsson T, Kockum I (Dec 2010). "Confirmation of association between multiple sclerosis and CYP27B1". European Journal of Human Genetics. 18 (12): 1349–1352. doi:10.1038/ejhg.2010.113. PMC 3002863. PMID 20648053.
- Fichna M, Zurawek M, Januszkiewicz-Lewandowska D, Gryczyñska M, Fichna P, Sowiñski J, et al. (Aug 2010). "Association of the CYP27B1 C(-1260)A polymorphism with autoimmune Addison's disease". Experimental and Clinical Endocrinology & Diabetes. 118 (8): 544–549. doi:10.1055/s-0029-1241206. PMID 19998245.
- Holt SK, Kwon EM, Koopmeiners JS, Lin DW, Feng Z, Ostrander EA, et al. (Sep 2010). "Vitamin D pathway gene variants and prostate cancer prognosis". The Prostate. 70 (13): 1448–1460. doi:10.1002/pros.21180. PMC 2927712. PMID 20687218.
- Bu FX, Armas L, Lappe J, Zhou Y, Gao G, Wang HW, et al. (Nov 2010). "Comprehensive association analysis of nine candidate genes with serum 25-hydroxy vitamin D levels among healthy Caucasian subjects". Human Genetics. 128 (5): 549–556. doi:10.1007/s00439-010-0881-9. PMID 20809279.
- Fichna M, Zurawek M, Januszkiewicz-Lewandowska D, Fichna P, Nowak J (Oct 2010). "PTPN22, PDCD1 and CYP27B1 polymorphisms and susceptibility to type 1 diabetes in Polish patients". International Journal of Immunogenetics. 37 (5): 367–372. doi:10.1111/j.1744-313X.2010.00935.x. PMID 20518841.
- Wjst M, Heimbeck I, Kutschke D, Pukelsheim K (Jul 2010). "Epigenetic regulation of vitamin D converting enzymes". The Journal of Steroid Biochemistry and Molecular Biology. 121 (1–2): 80–83. doi:10.1016/j.jsbmb.2010.03.056. PMID 20304056.
- Liu CY, Wu MC, Chen F, Ter-Minassian M, Asomaning K, Zhai R, et al. (Jul 2010). "A Large-scale genetic association study of esophageal adenocarcinoma risk". Carcinogenesis. 31 (7): 1259–1263. doi:10.1093/carcin/bgq092. PMC 2893800. PMID 20453000.
- Sunyer J, Basagaña X, González JR, Júlvez J, Guerra S, Bustamante M, et al. (Oct 2010). "Early life environment, neurodevelopment and the interrelation with atopy". Environmental Research. 110 (7): 733–738. Bibcode:2010ER....110..733S. doi:10.1016/j.envres.2010.07.005. PMID 20701904.
- Simon KC, Munger KL, Ascherio A (Feb 2010). "Polymorphisms in vitamin D metabolism related genes and risk of multiple sclerosis". Multiple Sclerosis. 16 (2). Houndmills, Basingstoke, England: 133–138. doi:10.1177/1352458509355069. PMC 2819633. PMID 20007432.
- Hendrickson SL, Lautenberger JA, Chinn LW, Malasky M, Sezgin E, Kingsley LA, et al. (Sep 2010). Badger JH (ed.). "Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression". PLOS ONE. 5 (9) e12862. Bibcode:2010PLoSO...512862H. doi:10.1371/journal.pone.0012862. PMC 2943476. PMID 20877624.
- Dusso AS, Brown AJ, Slatopolsky E (Jul 2005). "Vitamin D". American Journal of Physiology. Renal Physiology. 289 (1): F8–28. doi:10.1152/ajprenal.00336.2004. PMID 15951480.
- Bailey SD, Xie C, Do R, Montpetit A, Diaz R, Mohan V, et al. (Oct 2010). "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): 2250–2253. doi:10.2337/dc10-0452. PMC 2945168. PMID 20628086.
External links
- 25-Hydroxyvitamin+D3+1-alpha-Hydroxylase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Human CYP27B1 genome location and CYP27B1 gene details page in the UCSC Genome Browser.
- Human VDR genome location and VDR gene details page in the UCSC Genome Browser.
