25-Hydroxyvitamin D 1-alpha-hydroxylase

25-Hydroxyvitamin D 1-alpha-hydroxylase (VD 1A hydroxylase) also known as calcidiol 1-monooxygenase [5] or cytochrome p450 27B1 (CYP27B1) or simply 1-alpha-hydroxylase is a cytochrome P450 enzyme that in humans is encoded by the CYP27B1 gene.[6][7][8]

CYP27B1
Identifiers
AliasesCYP27B1, CP2B, CYP1, CYP1alpha, CYP27B, P450c1, PDDR, VDD1, VDDR, VDDRI, VDR, cytochrome P450 family 27 subfamily B member 1
External IDsOMIM: 609506; MGI: 1098274; HomoloGene: 37139; GeneCards: CYP27B1; OMA:CYP27B1 - orthologs
EC number1.14.15.18
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000785

NM_010009

RefSeq (protein)

NP_000776

NP_034139

Location (UCSC)Chr 12: 57.76 – 57.77 MbChr 10: 126.88 – 126.89 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
calcidiol 1-monooxygenase
Identifiers
EC no.1.14.15.18
CAS no.9081-36-1
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

VD 1A hydroxylase is located in the proximal tubule of the kidney and a variety of other tissues, including skin (keratinocytes), immune cells,[9] and bone (osteoblasts).[10]

Reactions

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The enzyme catalyzes the hydroxylation of calcifediol to calcitriol (the bioactive form of Vitamin D):[11]

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.[12]

Clinical significance

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Loss-of-function mutations in CYP27B1 cause Vitamin D-dependent rickets, type IA.[13]

Interactive pathway map

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Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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|alt=Vitamin D Synthesis Pathway (view / edit)]]
Vitamin D Synthesis Pathway (view / edit)
  1. ^ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000111012Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000006724Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "25-Hydroxyvitamin D3 1-Alpha-Hydroxylase - an overview | ScienceDirect Topics".
  6. ^ "Entrez Gene: cytochrome P450".
  7. ^ 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): 1827–30. doi:10.1126/science.277.5333.1827. PMID 9295274.
  8. ^ Monkawa T, Yoshida T, Wakino S, Shinki T, Anazawa H, Deluca HF, Suda T, Hayashi M, Saruta T (Oct 1997). "Molecular cloning of cDNA and genomic DNA for human 25-hydroxyvitamin D3 1 alpha-hydroxylase". Biochemical and Biophysical Research Communications. 239 (2): 527–33. doi:10.1006/bbrc.1997.7508. PMID 9344864.
  9. ^ Sigmundsdottir H, Pan J, Debes GF, Alt C, Habtezion A, Soler D, Butcher EC (Mar 2007). "DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27" (PDF). Nature Immunology. 8 (3): 285–93. doi:10.1038/ni1433. PMID 17259988. S2CID 9540123.[permanent dead link]
  10. ^ Kogawa M, Findlay DM, Anderson PH, Ormsby R, Vincent C, Morris HA, Atkins GJ (Oct 2010). "Osteoclastic metabolism of 25(OH)-vitamin D3: a potential mechanism for optimization of bone resorption". Endocrinology. 151 (10): 4613–25. doi:10.1210/en.2010-0334. PMID 20739402.
  11. ^ 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): 7528–32. doi:10.1016/S0021-9258(19)44557-2. PMID 4404596.
  12. ^ 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): 950–6. doi:10.1046/j.1432-1327.1999.00794.x. PMID 10518789.
  13. ^ "# 264700 - VITAMIN D HYDROXYLATION-DEFICIENT RICKETS, TYPE 1A; VDDR1A". www.omim.org.

Further reading

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