Information on EC 1.14.14.29 - 25/26-hydroxycholesterol 7alpha-hydroxylase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.14.14.29
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RECOMMENDED NAME
GeneOntology No.
25/26-hydroxycholesterol 7alpha-hydroxylase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
(25R)-cholest-5-ene-3beta,26-diol + [reduced NADPH-hemoprotein reductase] + O2 = (25R)-cholest-5-ene-3betA,7alpha,26-triol + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
; (2)
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cholest-5-ene-3beta,25-diol + [reduced NADPH-hemoprotein reductase] + O2 = cholest-5-ene-3beta,7alpha,25-triol + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
; (1)
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
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redox reaction
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reduction
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Primary bile acid biosynthesis
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Steroid hormone biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
cholest-5-ene-3beta,25/26-diol,[NADPH-hemoprotein reductase]:oxygen oxidoreductase (7alpha-hydroxylating)
A P-450 (heme-thiolate) protein. Unlike EC 1.14.14.26, 24-hydroxycholesterol 7alpha-monooxygenase, which is specific for its oxysterol substrate, this enzyme can also metabolize the oxysterols 24,25-epoxycholesterol, 22-hydroxycholesterol and 24-hydroxycholesterol, but to a lesser extent [2]. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH---hemoprotein reductase.
CAS REGISTRY NUMBER
COMMENTARY hide
149316-80-3
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440356-82-1
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
CYP7B1 is an enzyme expressed in many human tissues and implicated in cholesterol metabolism. In the liver, this protein is part of the alternate/acidic pathway for primary bile acid production while in brain, CYP7B1 provides the primary metabolic route for cholesterol derivatives dehydroepiandrosterone and related hydroxysteroids via 7alpha-hydroxylation
physiological function
additional information
spastic paraplegia type 5, SPG5, is caused by mutations in CYP7B1, a gene encoding the cytochrome P-450 oxysterol 7-alpha-hydroxylase, CYP7B1, an enzyme implicated in cholesterol metabolism. Mutations in CYP7B1 are found in both pure and complicated forms of the disease, clinical phenotypes, overview
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
17beta-estradiol + NADPH + H+ + O2
1,3,5(10)-estratrien-3,7-alpha,17beta-triol + NADP+ + H2O
show the reaction diagram
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-
-
-
?
22-hydroxycholesterol + NADPH + H+ + O2
7alpha,22-dihydroxycholesterol + NADP+ + H2O
show the reaction diagram
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-
-
-
?
24,25-epoxycholesterol + NADPH + H+ + O2
7alpha,hydroxy-24,25-epoxycholesterol + NADP+ + H2O
show the reaction diagram
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-
-
-
?
24-hydroxycholesterol + NADPH + H+ + O2
7alpha,24-dihydroxycholesterol + NADPH + H2O
show the reaction diagram
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-
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?
25-hydroxycholesterol + NADPH + H+ + O2
? + NADP+ + H2O
show the reaction diagram
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-
-
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?
27-hydroxycholesterol + NADPH + H+ + O2
3beta,7alpha-dihydroxy-5-cholestenoic acid + NADP+ + H2O
show the reaction diagram
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-
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?
4-androstene-3,17-dione + NADPH + H+ + O2
7alpha-hydroxy-4-androstene-3,17-dione + NADP+ + H2O
show the reaction diagram
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-
-
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?
5alpha-androstane-3alpha,17beta-diol + NADPH + O2
5alpha-androstane-3alpha,7alpha,17beta-triol + NADP+ + H2O
show the reaction diagram
5alpha-androstane-3alpha,17beta-diol + NADPH + O2
? + NADP+ + H2O
show the reaction diagram
5alpha-androstane-3beta,17beta-diol + NADPH + H+ + O2
5alpha,androstane-3beta,7alpha,17beta-triol + NADP+ + H2O
show the reaction diagram
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-
-
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?
5alpha-androstane-3beta,17beta-diol + NADPH + H+ + O2
?
show the reaction diagram
cholest-5-ene-3beta,25-diol + NADPH + H+ + O2
cholest-5-ene-3beta,7alpha,25-triol + NADP+ + H2O
show the reaction diagram
cholest-5-ene-3beta,27-diol + NADPH + H+ + O2
cholest-5-ene-3beta,7alpha,27-triol + NADP+ + H2O
show the reaction diagram
dehydroepiandrosterone + NADPH + H+ + O2
3beta,7alpha-dihydroxy-5-androsten-17-one + NADP+ + H2O
show the reaction diagram
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?
dehydroepiandrosterone + NADPH + H+ + o2
7alpha-hydroxy-dehydroepiandrosterone
show the reaction diagram
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?
dehydroepiandrosterone + NADPH + H+ + O2
7alpha-hydroxy-dehydroepiandrosterone + NADP+ + H2O
show the reaction diagram
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?
dehydroepiandrosterone + NADPH + O2
7alpha-hydroxy-dehydroepiandrosterone + NADP+ + H2O
show the reaction diagram
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?
dehydroepiandrosterone + NADPH + O2
? + NADP+ + H2O
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
25-hydroxycholesterol + NADPH + H+ + O2
? + NADP+ + H2O
show the reaction diagram
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?
27-hydroxycholesterol + NADPH + H+ + O2
3beta,7alpha-dihydroxy-5-cholestenoic acid + NADP+ + H2O
show the reaction diagram
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?
cholest-5-ene-3beta,25-diol + NADPH + H+ + O2
cholest-5-ene-3beta,7alpha,25-triol + NADP+ + H2O
show the reaction diagram
cholest-5-ene-3beta,27-diol + NADPH + H+ + O2
cholest-5-ene-3beta,7alpha,27-triol + NADP+ + H2O
show the reaction diagram
dehydroepiandrosterone + NADPH + H+ + O2
7alpha-hydroxy-dehydroepiandrosterone + NADP+ + H2O
show the reaction diagram
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?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cytochrome P-450
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cytochrome P450
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NADPH
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3alpha-adiol
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5alpha-androstane-3alpha,17beta-diol
5alpha-Androstane-3beta,17beta-diol
dehydroepiandrosterone
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inhibits hydroxylation of 5alpha-androstane-3beta,17beta-diol
LY294002
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specific inhibitor of phosphatidylinositol 3-kinase, abolishes estrogen receptor-mediated upregulation of a CYP7B1 promoter-luciferase reporter in Hep-G2 cells but not in HEK-293 cells
PD98059
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markedly suppresses basal CYP7B1 promoter activity, abolishes upregulation of CYP7B1 by estrogen receptor in Hep-G2 cells
SP600125
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markedly suppresses basal CYP7B1 promoter activity, abolishes upregulation of CYP7B1 by estrogen receptor in Hep-G2 cells but not in HEK-293 cells
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
estrogen
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overexpression of PI3K or Akt significantly increases estrogenic upregulation of CYP7B1 in Hep-G2 cells. Estrogen receptor interacts with the PI3K/Akt pathway without binding to the CYP7B1 gene. In HEK293 cells, CYP7B1 transcription is much less affected by Akt, indicating that the mechanism for upregulation of CYP7B1 is different in different cell types
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.011
17beta-estradiol
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pH 7.4, 37°C
0.004
4-androstene-3,17-dione
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pH 7.4, 37°C
0.003 - 0.022
5alpha-Androstane-3beta,17beta-diol
0.001
cholest-5-ene-3beta,25-diol
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pH 7.4, 37°C
0.005 - 0.014
dehydroepiandrosterone
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0166
5alpha-Androstane-3beta,17beta-diol
Sus scrofa
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0.033
dehydroepiandrosterone
Sus scrofa
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.006
5alpha-Androstane-3beta,17beta-diol
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inhibition of hydroxylation of dehydroepiandrosterone
0.024
dehydroepiandrosterone
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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bone marrow-derived
Manually annotated by BRENDA team
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CYP7B1 is overexpressed in high-grade prostatic intraepithelial neoplasia and in prostate cancer
Manually annotated by BRENDA team
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CYP7B1 is overexpressed in high-grade prostatic intraepithelial neoplasia and in prostate cancer
Manually annotated by BRENDA team
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CYP7B1 is overexpressed in high-grade prostatic intraepithelial neoplasia and in prostate cancer
Manually annotated by BRENDA team
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activity is detected in keratinocytes of the spinous and granula layers, and to lesser extent in the basal layer and basal cell bodies. High activity in hair follicle associated cells
Manually annotated by BRENDA team
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CYP7B1 occurrs in trabecular stroma cells
Manually annotated by BRENDA team
additional information
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CYP7B1 is elevated by 1.5 days postpartum compared with other ages, levels decrease in the midneonatal period and then increase by 20.5 days postpartum
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
14 deletion mutants of the regulatory sequences of CYP7B1/Luc reporter gene are constructed for transfection assays. The constructs are transiently transfected into HepG2, NT1088, and HEK 293 cells
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CYP7B1 genotyping and screening for CYP7B1 mutations in a large cohort of 105 Italian HSP index patients, including 50 patients with a complicated phenotype and 55 with a pure form, overall mutation frequencies of CYP7B1, overview
expression in 293/T cells
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from pCMV6 vector overexpressed in HEK-293 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of CYP7B1 by estrogen receptor can be mediated via the PI3K/Akt signal pathway. Overexpression of PI3K or Akt significantly increases estrogenic up-regulation of CYP7B1
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expression of CYP7B1 by estrogen receptor can be mediated via the PI3K/Akt signal pathway. Treatment with LY294002, a specific inhibitor of phosphatidylinositol 3-kinase PI3K, abolishes estrogen-receptor-mediated up-regulation of a CYP7B1 promoter-luciferase reporter
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lipopolysaccharide treatment does not increase the expression
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A316AA
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the mutation is associated with the SPG5A subtype of hereditary spastic paraplegia
G147D
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the mutation is associated with the SPG5A subtype of hereditary spastic paraplegia
G443A
c.1328G-C, naturally occuring mutation of CYP7B1 involved in spastic paraplegia type 5
G87V
c.260G-T, naturally occuring mutation of CYP7B1 involved in spastic paraplegia type 5
H285L
c.854A-T, naturally occuring mutation of CYP7B1 involved in spastic paraplegia type 5
R112X
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the mutation is associated with the SPG5A subtype of hereditary spastic paraplegia
R324H
c.971G-A, naturally occuring mutation of CYP7B1 involved in spastic paraplegia type 5
R486C
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the mutation is associated with the SPG5A subtype of hereditary spastic paraplegia
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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identification of mutations in CYP7B1 associated with hereditary spastic paraplegias provide direct evidence for abnormalities in cholesterol metabolism in the pathogenesis of motor-neuron degeneration