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Information on EC 1.14.15.15 - cholestanetriol 26-monooxygenase and Organism(s) Rattus norvegicus and UniProt Accession P17178

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IUBMB Comments
This mitochondrial cytochrome P-450 enzyme requires adrenodoxin. It catalyses the first three sterol side chain oxidations in bile acid biosynthesis via the neutral (classic) pathway. Can also act on cholesterol, cholest-5-ene-3beta,7alpha-diol, 7alpha-hydroxycholest-4-en-3-one, and 5beta-cholestane-3alpha,7alpha-diol. The enzyme can also hydroxylate cholesterol at positions 24 and 25. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP+ reductase.
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Rattus norvegicus
UNIPROT: P17178
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The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
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5beta-cholestane-3alpha,7alpha,12alpha-triol
+
6
reduced adrenodoxin
+
6
H+
+
3
O2
=
(25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oate
+
6
oxidized adrenodoxin
+
4
H2O
+
6
reduced adrenodoxin
+
6
+
3
=
+
6
oxidized adrenodoxin
+
4
Synonyms
sterol 27-hydroxylase, cyp27, vitamin d3 25-hydroxylase, cyp27a, cytochrome p-450a, p450 27a1, cytochrome p450c27, 5beta-cholestane-3alpha,7alpha,12alpha-triol hydroxylase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5beta-cholestane-3 alpha,7alpha,12alpha,26-tetrol dehydrogenase
-
-
-
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5beta-cholestane-3 alpha,7alpha,12alpha-triol-26-al oxidoreductase
-
-
-
-
5beta-cholestane-3alpha,7alpha,12alpha-triol 26-hydroxylase
-
-
-
-
5beta-cholestane-3alpha,7alpha,12alpha-triol 27-monooxygenase
-
enzyme was renamed into 27-monooxygenase because it hydroxylates the methyl group in position 27
5beta-cholestane-3alpha,7alpha,12alpha-triol hydroxylase
-
-
-
-
cholestanetriol 26-hydroxylase
-
-
-
-
cholestanetriol 27-hydroxylase
-
-
-
-
cytochrome P-450A
-
-
-
-
dehydrogenase, cholestanetetrol 26-
-
-
-
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hydroxylase, 5beta-cholestane-3alpha,7alpha,12alpha-triol
-
-
-
-
oxygenase, cholestanetriol 26-mono-
-
-
-
-
sterol 27-hydroxylase
-
-
TEHC-NAD oxidoreductase
-
-
-
-
vitamin D3 25-hydroxylase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
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-
-
-
SYSTEMATIC NAME
IUBMB Comments
5beta-cholestane-3alpha,7alpha,12alpha-triol,adrenodoxin:oxygen oxidoreductase (26-hydroxylating)
This mitochondrial cytochrome P-450 enzyme requires adrenodoxin. It catalyses the first three sterol side chain oxidations in bile acid biosynthesis via the neutral (classic) pathway. Can also act on cholesterol, cholest-5-ene-3beta,7alpha-diol, 7alpha-hydroxycholest-4-en-3-one, and 5beta-cholestane-3alpha,7alpha-diol. The enzyme can also hydroxylate cholesterol at positions 24 and 25. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP+ reductase.
CAS REGISTRY NUMBER
COMMENTARY hide
52227-77-7
-
62213-60-9
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1alpha-hydroxyvitamin D3 + reduced adrenodoxin + O2
1alpha,25-dihydroxyvitamin D3 + oxidized adrenodoxin + H2O
show the reaction diagram
5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + oxidized adrenodoxin + H2O
show the reaction diagram
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + H+ + O2
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
5beta-cholestane-3alpha,7alpha,12alpha,27-tetrol + oxidized adrenodoxin + H2O
show the reaction diagram
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
?
show the reaction diagram
5beta-cholestane-3alpha,7alpha-diol + reduced adrenodoxin + O2
?
show the reaction diagram
-
-
-
-
?
5beta-cholestane-3alpha-ol + reduced adrenodoxin + O2
?
show the reaction diagram
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-
-
-
?
cholesterol + reduced adrenodoxin + O2
?
show the reaction diagram
-
-
-
-
?
additional information
?
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-
sterol 27-hydroxylase is regulated by liver X receptor signaling, overview
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + oxidized adrenodoxin + H2O
show the reaction diagram
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + H+ + O2
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + oxidized adrenodoxin + H2O
show the reaction diagram
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
?
show the reaction diagram
additional information
?
-
-
sterol 27-hydroxylase is regulated by liver X receptor signaling, overview
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ATP
-
peroxisomal and mitochondrial enzyme require ATP
cytochrome P450
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
peroxisomal and mitochondrial enzyme requires Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1alpha-hydroxyvitamin D3
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competes with 5beta-cholestane-3alpha,7alpha,12alpha-triol
5beta-cholestane-3alpha,7alpha,12alpha-triol
5beta-cholestane-3alpha,7alpha-diol
-
inhibits 5beta-cholestane-3alpha,7alpha,12alpha-triol 27-monooxygenase activity only slightly
7,8-Benzoflavone
-
68% inhibition at 0.04 mM
Aminoglutethimide
-
slight inhibition
Ca2+
-
complete inhibition at 1 mM
dicoumarol
-
10% inhibition at 0.05 mM
Metyrapone
-
slight inhibition of 27-monooxygenase
N-bromosuccinimide
-
50% loss of activity at 0.1 mM
p-chloromercuribenzoate
p-chloromercuriphenyl sulfonate
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80% inhibition at 0.1 mM
Phenyl isocyanide
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
astrocyte-restricted upregulation of Cyp27a1 due to to differential expression of transcriptional co-activators, increase of enzyme mRNA and protein levels in treated astrocytes is paralleled by transactivation of the proximal Cyp27a1 promoter in transfected astrocytes
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0045 - 0.06
5beta-cholestane-3alpha,7alpha,12alpha-triol
0.01
5beta-cholestane-3alpha,7alpha-diol
-
-
0.01 - 0.02
O2
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00233 - 0.0233
1alpha-hydroxyvitamin D3
0.333 - 0.6
5beta-cholestane-3alpha,7alpha,12alpha-triol
0.217
5beta-cholestane-3alpha,7alpha-diol
-
-
0.0117
cholesterol
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.004
5beta-cholestane-3alpha,7alpha,12alpha-triol
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00233
-
1alpha-hydroxyvitamin D3 as substrate
0.114
-
5beta-cholestane-3alpha,7alpha,12alpha-triol as substrate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 8
-
27-hydroxylation
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene CYP27A1
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
primary astrocytes express different sterol hydroxylases and are able to uptake exogenous 27-hydroxycholesterol
Manually annotated by BRENDA team
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Cyp27a1 is expressed in all the cell types but at highest levels in microglia
Manually annotated by BRENDA team
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expression pattern of Cyp27a1 and other related genes in primary cultures of glia and neurons
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
-
only the mitochondrial hydroxylase system is specific for C-26 position, the microsomal system is unspecific for C-26 position but rather more active for other adjacent positions
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
post-transcriptional silencing of the CYP27A1 gene in rat adrenocortical cells reduces the expression of CYP27A1 mRNA by 70%, reduces total bile acids by 2fold, and marinobufagenin levels by 67% when compared with nontreated cells or cells transfected with nontargeting siRNA
metabolism
the enzyme initiates the biosynthesis of bile acids, pathway overview
physiological function
bioactive steroid marinobufagenin, an endogenous Na/K-ATPase bufadienolide inhibitor that is synthesized by adrenocortical and placental cells, is derived from cholesterol through the traditional steroidogenesis pathway initiated by enzyme CYP11A1, and via the acidic bile acid pathway, which is controlled by enzyme CYP27A1
malfunction
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enzyme deficiency causes a disease characterized by progressive neurologic impairment. Impairment of CYP27 activity in astrocytes may alter critical features of the astrocytes, from the handling and delivery of cholesterol to neurons to the release of signaling molecules
metabolism
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the enzyme is involved in cholesterol handling and metabolism
physiological function
-
pathophysiological role of CYP27A1 in the CNS
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CP27A_RAT
533
0
60733
Swiss-Prot
Mitochondrion (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
52500
-
SDS-PAGE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
silencing of gene CYP27A1 by targeting siRNA
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45
-
90% loss of activity after 2 min
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C, no loss of activity for 5 months
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
partial purification of a ferredoxin-like iron-sulfur protein and a NADPH-ferredoxin reductase which are functional for 26-hydroxylation when reconstituted with partially purified liver mitochondrial cytochrome P-450
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene CYP27A1, quantitative real-time PCR enzyme expression analysis
CYP27 expression analysis in the brain
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
in vivo, in a high-salt administration experiment, male and female Dahl salt-sensitive rats become hypertensive after 4 weeks on a high-NaCl diet, their plasma marinobufagenin levels double, and adrenocortical CYP27A1 mRNA and protein increase 1.6fold and 2.0fold, respectively
astrocyte-restricted upregulation of Cyp27a1 due to to differential expression of transcriptional co-activators, increase of enzyme mRNA and protein levels in treated astrocytes is paralleled by transactivation of the proximal Cyp27a1 promoter in transfected astrocytes
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Masui, T.; Herman, R.; Staple, E.
The oxidation of 5-beta-cholestane-3-alpha, 7-alpha, 12-alpha, 26-tetraol to 5-beta-cholestane-3-alpha, 7-alpha, 12-alpha-triol-26-oic acid via 5-beta-cholestane-3-alpha, 7-alpha, 12-alpha-triol-26-al by rat liver
Biochim. Biophys. Acta
117
266-268
1966
Rattus norvegicus
Manually annotated by BRENDA team
Okuda, K.; Takigawa, N.
Separation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha,26-tetrol oxidoreductase, and acetaldehyde-NAD oxidoreductase from the soluble fraction of rat liver by gel filtration
Biochem. Biophys. Res. Commun.
33
788-793
1968
Rattus norvegicus
Manually annotated by BRENDA team
Okuda, K.; Hoshita, N.
Oxidation of 5-beta-cholestane-3alpha,7alpha, 12alpha-triol by rat-liver mitochondria
Biochim. Biophys. Acta
164
381-388
1968
Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Taniguchi, S.; Hoshita, N.; Okuda, K.
Enzymatic characteristics of CO-sensitive 26-hydroxylase system for 5beta-cholestane-3alpha,7alpha 12alpha-triol in rat-liver mitochondria and its intramitochondrial localization
Eur. J. Biochem.
40
607-617
1973
Rattus norvegicus
Manually annotated by BRENDA team
Okuda, K.; Weber, P.; Ullrich, V.
Photochemical action spectrum of the co-inhibited 5beta-cholestane-3alpha,7alpha,12alpha-triol 26-hydroxylase system
Biochem. Biophys. Res. Commun.
74
1071-1076
1977
Rattus norvegicus
Manually annotated by BRENDA team
Okuda, K.; Ruf, H.H.; Ullrich, V.
Spectral evidence for a liver mitochondrial cytochrome P450 involved in bile acid metabolism
Hoppe-Seyler's Z. Physiol. Chem.
358
689-694
1977
Rattus norvegicus
Manually annotated by BRENDA team
Sato, R.; Atsuta, Y.; Imai, Y.; Taniguchi, S.; Okuda, K.
Hepatic mitochondrial cytochrome P-450: isolation and functional characterization
Proc. Natl. Acad. Sci. USA
74
5477-5481
1977
Rattus norvegicus
Manually annotated by BRENDA team
Atsuta, Y.; Okuda, K.
Partial purification and characterization of 5beta-cholestane-3alpha,7alpha,12alpha-triol and 5beta-cholestane-3alpha,7alpha-diol 27-monooxygenase
J. Lipid Res.
23
345-351
1982
Rattus norvegicus
Manually annotated by BRENDA team
Okuda, K.; Masumoto, O.; Ohyama, Y.
Purification and characterization of 5beta-cholestane-3alpha,7alpha,12alpha-triol 27-hydroxylase from female rat liver mitochondria
J. Biol. Chem.
263
18138-18142
1988
Rattus norvegicus
Manually annotated by BRENDA team
Thompson, S.L.; Krisans, S.K.
Evidence for peroxisomal hydroxylase activity in rat liver
Biochem. Biophys. Res. Commun.
130
708-716
1985
Rattus norvegicus
Manually annotated by BRENDA team
Hansson, R.; Holmberg, I.; Wikvall, K.
25-Hydroxylation vitamin D3 and side chain hydroxylations of 5beta-cholestane-3alpha,7alpha,12 alpha-triol by purified rabbit and rat liver microsomal cytochromes P-450
J. Biol. Chem.
256
4345-4349
1981
Oryctolagus cuniculus, Rattus norvegicus
Manually annotated by BRENDA team
Atsuta, Y.; Okuda, K.
Isolation of rat liver mitochondrial ferredoxin and its reductase active in the 5beta-cholestane-3alpha,7alpha,12alpha-triol 26 hydroxylase
J. Biol. Chem.
253
4653-4658
1978
Rattus norvegicus
Manually annotated by BRENDA team
Ohyama, Y.; Masumoto, O.; Usui, E.; Okuda, K.
Multi-functional property of rat liver mitochondrial cytochrome P-450
J. Biochem.
109
389-393
1991
Rattus norvegicus
Manually annotated by BRENDA team
Akiyoshi-Shibata, M.; Usui, E.; Sakaki, T.; Yabusaki, Y.; Noshiro, M.; Okuda, K.; Ohkawa, H.
Expression of rat liver vitamin D3 25-hydroxylase cDNA in Saccharomyces cerevisiae
FEBS Lett.
280
367-370
1991
Rattus norvegicus
Manually annotated by BRENDA team
Usui, E.; Noshiro, M.; Ohyama, Y.; Okuda, K.
Unique property of liver mitochondrial P450 to catalyze the two physiologically important reactions involved in both cholesterol catabolism and vitamin D activation
FEBS Lett.
274
175-177
1990
Rattus norvegicus
Manually annotated by BRENDA team
Gilardi, F.; Viviani, B.; Galmozzi, A.; Boraso, M.; Bartesaghi, S.; Torri, A.; Caruso, D.; Crestani, M.; Marinovich, M.; de Fabiani, E.
Expression of sterol 27-hydroxylase in glial cells and its regulation by liver X receptor signaling
Neuroscience
164
530-540
2009
Rattus norvegicus
Manually annotated by BRENDA team
Fedorova, O.V.; Zernetkina, V.I.; Shilova, V.Y.; Grigorova, Y.N.; Juhasz, O.; Wei, W.; Marshall, C.A.; Lakatta, E.G.; Bagrov, A.Y.
Synthesis of an endogenous steroidal Na pump inhibitor marinobufagenin, implicated in human cardiovascular diseases, is initiated by CYP27A1 via bile acid pathway
Circ. Cardiovasc. Genet.
8
736-745
2015
Homo sapiens (Q02318), Rattus norvegicus (P17178)
Manually annotated by BRENDA team