25-Hydroxyvitamin D3 1-alpha-hydroxylase

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PMC	articles
PubMed	articles
NCBI	proteins

calcidiol 1-monooxygenase
Identifiers
EC number	1.14.15.18
CAS number	9081-36-1
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search
PMC	articles
PubMed	articles
NCBI	proteins

CYP27B1
Identifiers
Aliases	CYP27B1 , CP2B, CYP1, CYP1alpha, CYP27B, P450c1, PDDR, VDD1, VDDR, VDDRI, VDR, cytochrome P450 family 27 subfamily B member 1
External IDs	OMIM: 609506 MGI: 1098274 HomoloGene: 37139 GeneCards: CYP27B1
EC number	1.14.15.18
Gene location (Human)
Chr.	Chromosome 12 (human) [1]
End	57,768,986 bp [1]
Gene location (Mouse)
Chr.	Chromosome 10 (mouse) [2]
End	127,053,006 bp [2]
Gene ontology
Molecular function	• iron ion binding ; • metal ion binding ; • monooxygenase activity ; • heme binding ; • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen ; • oxidoreductase activity ; • calcidiol 1-monooxygenase activity ;
Cellular component	• cytoplasm ; • membrane ; • mitochondrial membranes ; • mitochondrial outer membrane ; • mitochondrion ;
Biological process	• bone mineralization ; • response to vitamin D ; • calcium ion homeostasis ; • response to interferon-gamma ; • vitamin D metabolic process ; • regulation of bone mineralization ; • positive regulation of keratinocyte differentiation ; • G1 to G0 transition ; • response to estrogen ; • response to lipopolysaccharide ; • negative regulation of calcidiol 1-monooxygenase activity ; • decidualization ; • vitamin metabolic process ; • negative regulation of cell growth ; • calcitriol biosynthetic process from calciol ; • positive regulation of vitamin D 24-hydroxylase activity ; • vitamin D catabolic process ; • positive regulation of vitamin D receptor signaling pathway ; • oxidation-reduction process ; • calcium ion transport ; • negative regulation of cell proliferation ;
	Sources:Amigo / QuickGO
Orthologs
	1594
	13115
	ENSG00000111012
	ENSMUSG00000006724
	O15528
	O35084
	NM_000785
	NM_010009
	NP_000776
	NP_034139
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated October 13, 2020

25-Hydroxyvitamin D₃ 1-alpha-hydroxylase (VD3 1A hydroxylase) also known as cytochrome p450 27B1 (CYP27B1) or simply 1-alpha-hydroxylase is a cytochrome P450 enzyme that in humans is encoded by the CYP27B1 gene.^[5]^[6]^[7]

Interactive pathway map

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

[[File:

25-Hydroxyvitamin D3 1-alpha-hydroxylase

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|{{{bSize}}}px|alt=Vitamin D Synthesis Pathway (view / edit)]]

Vitamin D Synthesis Pathway (view / edit)

↑ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".

Related Research Articles

Cholecalciferol Vitamin D3, a chemical compound

Cholecalciferol, also known as vitamin D₃ and colecalciferol, is a type of vitamin D which is made by the skin when exposed to sunlight; it is also found in some foods and can be taken as a dietary supplement. It is used to treat and prevent vitamin D deficiency and associated diseases, including rickets. It is also used for familial hypophosphatemia, hypoparathyroidism that is causing low blood calcium, and Fanconi syndrome. Vitamin-D supplements may not be effective in people with severe kidney disease. It is usually taken by mouth.

Calcitriol is the active form of vitamin D, normally made in the kidney. A manufactured form is used to treat kidney disease with low blood calcium, hyperparathyroidism due to kidney disease, low blood calcium due to hypoparathyroidism, osteoporosis, osteomalacia, and familial hypophosphatemia. It is taken by mouth or by injection into a vein.

Fibroblast growth factor 23 or FGF23 is a protein that in humans is encoded by the FGF23 gene. FGF23 is a member of the fibroblast growth factor (FGF) family which participates in phosphate and vitamin D metabolism and regulation.

The vitamin D receptor (VDR), also known as the calcitriol receptor and as NR1I1, is a member of the nuclear receptor family of transcription factors. Calcitriol, the active form of vitamin D, binds to the VDR, which then forms a heterodimer with the retinoid-X receptor. This then binds to hormone response elements on DNA resulting in expression or transrepression of specific gene products. The VDR not only regulates transcriptional responses but also involved in microRNA-directed post transcriptional mechanisms. In humans, the vitamin D receptor is encoded by the VDR gene.

Aldosterone synthase protein-coding gene in the species Homo sapiens

Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steriods. The enzyme catalyzes sequential hydroxylations of the steroid angular methyl group at C18 after initial 11β-hydroxylation. It is encoded by CYP11B2 gene in humans.

X-linked hypophosphatemia (XLH), is an X-linked dominant form of rickets that differs from most cases of rickets in that vitamin D supplementation does not cure it. It can cause bone deformity including short stature and genu varum (bow-leggedness). It is associated with a mutation in the PHEX gene sequence (Xp.22) and subsequent inactivity of the PHEX protein.

Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the CYP7A1 gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enzyme, which belongs to the oxidoreductase class, and converts cholesterol to 7-alpha-hydroxycholesterol, the first and rate limiting step in bile acid synthesis.

Steroid 21-hydroxylase, also called steroid 21-monooxygenase, 21α-hydroxylase, and, less commonly, 21β-hydroxylase, is an enzyme that hydroxylates steroids at the C21 position and is involved in biosynthesis of aldosterone and cortisol. The enzyme converts progesterone and 17α-hydroxyprogesterone into 11-deoxycorticosterone and 11-deoxycortisol, respectively. The products of the conversions then continue through their appropriate pathways towards creation of aldosterone and cortisol. The enzyme is localized in endoplasmic reticulum membranes of adrenal cortex, and is encoded by CYP21A2 gene in humans.

Steroid 11β-hydroxylase, also known as steroid 11β-monooxygenase, is a steroid hydroxylase found in the zona glomerulosa and zona fasciculata. Named officially the cytochrome P450 11B1, mitochondrial, it is a protein that in humans is encoded by the CYP11B1 gene. The enzyme is involved in the biosynthesis of adrenal corticosteroids by catalyzing the addition of hydroxyl groups during oxidation reactions.

Calcitroic acid (1α-hydroxy-23-carboxy-24,25,26,27-tetranorvitamin D₃) is a major metabolite of 1α,25-dihydroxyvitamin D₃ (calcitriol). Often synthesized in the liver and kidneys, calcitroic acid is generated in the body after vitamin D is first converted into calcitriol, an intermediate in the fortification of bone through the formation and regulation of calcium in the body. These pathways managed by calcitriol are thought to be inactivated through its hydroxylation by the enzyme CYP24A1, also called calcitriol 24-hydroxylase. Specifically, it is thought to be the major route to inactivate vitamin D metabolites.

Cytochrome P450 family 24 subfamily A member 1 (abbreviated CYP24A1) is a member of the cytochrome P450 superfamily of enzymes encoded by the CYP24A1 gene. It is a mitochondrial monooxygenase which catalyzes reactions including 24-hydroxylation of calcitriol (1,25-dihydroxyvitamin D₃). It has also been identified as vitamin D3 24-hydroxylase.(EC 1.14.15.16)

Leukotriene-B(4) omega-hydroxylase 1 is an enzyme involved in the metabolism various endogenous substrates and xenobiotics. Most notable substrate of the enzyme is leukotriene B4, a potent mediator of inflammation. The enzyme is encoded by the CYP4F2 gene in humans.

25-hydroxycholesterol 7-alpha-hydroxylase also known as oxysterol and steroid 7-alpha-hydroxylase is an enzyme that in humans is encoded by the CYP7B1 gene. This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids.

Vitamin D 25-hydroxylase also known as cytochrome P450 2R1 is an enzyme that in humans is encoded by the CYP2R1 gene.

24,25-Dihydroxycholecalciferol chemical compound

24,25-Dihydroxycholecalciferol, also known as 24,25-dihydroxyvitamin D₃ and (24R)-hydroxycalcidiol (abbreviated as 24(R),25-(OH)₂D₃), is a compound which is closely related to 1,25-dihydroxyvitamin D₃, the active form of vitamin D₃, but like vitamin D₃ itself and 25-hydroxyvitamin D₃ is inactive as a hormone both in vitro and in vivo. It was identified by Michael F. Holick.

Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and multiple other biological effects. In humans, the most important compounds in this group are vitamin D₃ (also known as cholecalciferol) and vitamin D₂ (ergocalciferol).

Vitamin D3 24-hydroxylase (EC 1.14.15.16, CYP24A1) is an enzyme with systematic name calcitriol,NADPH:oxygen oxidoreductase (24-hydroxylating). This enzyme catalyses the following chemical reaction

11β-Hydroxyprogesterone chemical compound

11β-Hydroxyprogesterone (11β-OHP), also known as 21-deoxycorticosterone, as well as 11β-hydroxypregn-4-ene-3,20-dione, is a naturally occurring, endogenous steroid and derivative of progesterone. It is a potent mineralocorticoid. Syntheses of 11β-OHP from progesterone is catalyzed by the steroid 11β-hydroxylase (CYP11B1) enzyme, and, to a lesser extent, by the aldosterone synthase enzyme (CYP11B2).

Walter L. Miller is an American endocrinologist and professor emeritus of pediatrics at the University of California, San Francisco (UCSF). Miller is expert in the field of human steroid biosynthesis and disorders of steroid metabolism. Over the past 40 years Miller's group at UCSF has described molecular basis of several metabolic disorders including, congenital adrenal hyperplasia, pseudo vitamin D dependent rickets, severe, recessive form of Ehlers-Danlos syndrome, 17,20 lyase deficiency caused by CYP17A1 defects, P450scc deficiency caused by CYP11A1 defects, P450 oxidoreductase deficiency.

Late onset congenital adrenal hyperplasia (LOCAH), also known as non-classic congenital adrenal hyperplasia, is a milder form of congenital adrenal hyperplasia (CAH), a group of autosomal recessive disorders characterized by impaired cortisol synthesis that leads to variable degrees of postnatal androgen excess.

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.
↑ "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): 1827–30. doi:10.1126/science.277.5333.1827. PMID 9295274.
↑ 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.
↑ 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 ]}
↑ 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.
↑ 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. PMID 4404596.

External links

25-Hydroxyvitamin+D3+1-alpha-Hydroxylase at the US 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 .

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[WikiPathways-11] The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000111012 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000006724 - Ensembl, 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.

[entrez-5] "Entrez Gene: cytochrome P450".

[pmid9295274-6] 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.

[pmid9344864-7] 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.

[pmid17259988-8] 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 ]}

[pmid20739402-9] 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.

[pmid4404596-10] 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. PMID 4404596.

v t e Cytochromes, oxygenases: cytochrome P450 (Most belong to EC 1.14)
CYP1	A1 A2 A5 B1
CYP2	A6 A7 A13 B6 C8 C9 3 13 C18 C19 D6 E1 F1 J2 R1 S1 U1 W1
CYP3 (CYP3A)	A4 A5 A7 A37 A43
CYP4	A11 A22 B1 F2 F3 F8 F11 F12 F22 V2 X1 Z1
CYP5-20	CYP5 (A1) CYP6 (G1, M2) CYP7 (A1, B1) CYP8 (A1, B1) CYP11 (A1, A2, B1, B2, B3, C1) CYP16 CYP17 (A1) CYP19 (A1) CYP20 (A1)
CYP21-49	CYP21 (A2) CYP22 (A1) CYP24 (A1) CYP26 (A1, B1, C1) CYP27 (A1, B1, C1) CYP28 (A1) CYP35 (B1) CYP39 (A1) CYP46 (A1)
CYP51-69	CYP51 (A1, F1) CYP52 CYP53 (A1) CYP55 CYP56A1 CYP61
CYP71-99	CYP71 (C1, C2, C3, C4, Z6, AJ4, AV1, BA1) CYP72A1 CYP73A1 CYP74 (D1) CYP75 (A1, B1) CYP76 (B6, M7) CYP79 (A1, A2, B1, B2, B3, D1, D2, D3, D4) CYP80 (A1, B1, G2) CYP81 (E1, E3, E7, E9) CYP88D6 CYP90C1 CYP93E1 CYP97C1 CYP99A3
CYP101-281	CYP101A1 CYP102A1 CYP105 A1 D7 CYP106A2 CYP107 A1 G1 CYP111 CYP113A1 CYP119A1 CYP125A1 CYP152 A1 B1 CYP158A CYP161C CYP170 A1 B1 CYP176A1 CYP183A CYP199A2 CYP255A
CYP301-499	CYP303A1 CYP305M2 Halloween genes ( CYP302A1, CYP306A1, CYP307A1, CYP307A2, CYP314A1 , CYP315A1) CYP318A1
CYP501-699	CYP503 CYP504B1
CYP701-999	CYP710 CYP720A1

v t e Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14)
1.14.11: 2-oxoglutarate	Prolyl hydroxylase HIF prolyl-hydroxylase EGLN1 EGLN2 EGLN3 P4HTM Lysyl hydroxylase
1.14.13: NADH or NADPH	Flavin-containing monooxygenase FMO1 FMO2 FMO3 FMO4 FMO5 Nitric oxide synthase NOS1 NOS2 NOS3 Cholesterol 7 alpha-hydroxylase Methane monooxygenase 3A4 14α-demethylase 24-hydroxycholesterol 7α-hydroxylase
1.14.14: reduced flavin or flavoprotein	19A1 2D6 2E1
1.14.15: reduced iron-sulfur protein	11B1 11B2 11A1
1.14.16: reduced pteridine (BH4 dependent)	Phenylalanine hydroxylase Tyrosine hydroxylase Tryptophan hydroxylase
1.14.17: reduced ascorbate	Dopamine beta-hydroxylase
1.14.18-19: other	Tyrosinase Stearoyl-CoA desaturase-1
1.14.99 - miscellaneous	Cyclooxygenase Heme oxygenase (HMOX1) Squalene monooxygenase 17A1 21A2 Ecdysone 20-monooxygenase

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

25-Hydroxyvitamin D3 1-alpha-hydroxylase

Contents

Interactive pathway map

Related Research Articles

References

Further reading

External links