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(24S)-3beta-hydroxy-24-methyl-5alpha-cholesta-8(14),22-dien-15-one + reduced adrenodoxin + H+ + O2
?
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,27-tetraol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid + oxidized adrenodoxin + H2O
-
-
-
-
?
1alpha-hydroxyvitamin D3 + reduced adrenodoxin + O2
1alpha,25-dihydroxyvitamin D3 + oxidized adrenodoxin + H2O
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-27-al + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid + oxidized adrenodoxin + H2O
-
-
-
-
?
3beta-hydroxy-5alpha-cholest-8(14)-en-15-one + reduced adrenodoxin + H+ + O2
?
5-cholestene-3beta,7alpha-diol + reduced adrenodoxin + O2
5-cholestene-3alpha,7alpha,26-triol + oxidized adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + oxidized adrenodoxin + H2O
5beta-cholestane-3alpha,7alpha,12alpha,27-tetraol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestane-27-oic acid + oxidized adrenodoxin + H2O
-
oxidation to the corresponding C27-acid
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + H+ + O2
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + oxidized adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + oxidized adrenodoxin + H2O
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,27-tetraol + oxidized adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid + oxidzed adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + oxidized adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
5beta-cholestane-3alpha,7alpha,12alpha,27-tetrol + oxidized adrenodoxin + H2O
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
?
5beta-cholestane-3alpha,7alpha-diol + reduced adrenodoxin + O2
5beta-cholestane-3alpha,7alpha,26-triol + oxidized adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha-diol + reduced adrenodoxin + O2
?
-
-
-
-
?
5beta-cholestane-3alpha-ol + reduced adrenodoxin + O2
?
-
-
-
-
?
7-dehydrocholesterol + 4 reduced adrenodoxin + 2 H+ + 2 O2
25-hydroxy-7-dehydrocholesterol + 26/27-hydroxy-7-dehydrocholesterol + 4 oxidzed adrenodoxin + 2 H2O
-
-
metabolites detected in serum of a patient with Smith-Lemli-Opitz syndrome. 25-hydroxy-7-dehydrocholesterol activates liver X receptors LXRalpha, LXRbeta and vitamin D receptor and 26/27-hydroxy-7-dehydrocholesterol induces activation of LXRalpha and LXRbeta, although the activities of both compounds on LXRs are weak. 26/27-Hydroxy-7-dehydrocholesterol is (3S,25S)-cholesta-5,7-diene-3,26-diol or (3S,25R)-cholesta-5,7-diene-3,26-diol
-
?
7alpha-hydroxy-4-cholesten-3-one + reduced adrenodoxin + O2
7alpha,26-dihydroxy-4-cholesten-3-one + oxidized adrenodoxin + H2O
-
-
-
-
?
beta-sitosterol + reduced adrenodoxin + O2
26-hydroxy-beta-sitosterol + 29-hydroxy-beta-sitosterol + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + H+ + O2
26-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
-
?
cholesterol + reduced adrenodoxin + O2
24-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
-
?
cholesterol + reduced adrenodoxin + O2
25-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
-
?
cholesterol + reduced adrenodoxin + O2
26-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
27-hydroxycholesterol + oxidized adrenodoxin + H2O
cholesterol + reduced adrenodoxin + O2
?
-
-
-
-
?
ergosterol + reduced adrenodoxin + O2
24-hydroxyergosterol + 26-hydroxyergosterol + 28-hydroxyergosterol + oxidized adrenodoxin + H2O
-
-
-
?
additional information
?
-
(24S)-3beta-hydroxy-24-methyl-5alpha-cholesta-8(14),22-dien-15-one + reduced adrenodoxin + H+ + O2
?
-
the substrate is a potential drug for lowering cholesterol in the treatment and/or prevention of coronary artery disease, but it is rapidly metabolized in the liver
-
-
?
(24S)-3beta-hydroxy-24-methyl-5alpha-cholesta-8(14),22-dien-15-one + reduced adrenodoxin + H+ + O2
?
-
28-hydroxylation by CYP27A1, enzyme activity assay in presence of adrenodoxin, adrenodoxin reductase and NADPH
massspectrometric product analysis, 2 products, overview
-
?
1alpha-hydroxyvitamin D3 + reduced adrenodoxin + O2
1alpha,25-dihydroxyvitamin D3 + oxidized adrenodoxin + H2O
-
25-hydroxylation
-
-
?
1alpha-hydroxyvitamin D3 + reduced adrenodoxin + O2
1alpha,25-dihydroxyvitamin D3 + oxidized adrenodoxin + H2O
-
25-hydroxylation
-
?
3beta-hydroxy-5alpha-cholest-8(14)-en-15-one + reduced adrenodoxin + H+ + O2
?
-
the substrate is a potential drug for lowering cholesterol in the treatment and/or prevention of coronary artery disease, but it is rapidly metabolized in the liver
-
-
?
3beta-hydroxy-5alpha-cholest-8(14)-en-15-one + reduced adrenodoxin + H+ + O2
?
-
28-hydroxylation by CYP27A1, enzyme activity assay in presence of adrenodoxin, adrenodoxin reductase and NADPH
massspectrometric product analysis, 2 products, overview
-
?
5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + oxidized adrenodoxin + H2O
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + oxidized adrenodoxin + H2O
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + oxidized adrenodoxin + H2O
-
-
-
r
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + oxidized adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + oxidized adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
5beta-cholestane-3alpha,7alpha,12alpha,27-tetrol + oxidized adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
5beta-cholestane-3alpha,7alpha,12alpha,27-tetrol + oxidized adrenodoxin + H2O
-
microsomal enzyme also catalyzes 25-hydroxylation of 5beta-cholestane-3alpha,7 alpha,12alpha-triol
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
5beta-cholestane-3alpha,7alpha,12alpha,27-tetrol + oxidized adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
5beta-cholestane-3alpha,7alpha,12alpha,27-tetrol + oxidized adrenodoxin + H2O
-
isocitrate can act as electron donor
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
5beta-cholestane-3alpha,7alpha,12alpha,27-tetrol + oxidized adrenodoxin + H2O
-
microsomal enzyme also catalyzes 25-hydroxylation of 5beta-cholestane-3alpha,7 alpha,12alpha-triol
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
5beta-cholestane-3alpha,7alpha,12alpha,27-tetrol + oxidized adrenodoxin + H2O
-
mitochondrial enzyme is specific for 26-hydroxylation whereas the reaction with the microsomal enzyme hydroxylates at position 23, 24, 25 and 26
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
?
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
?
-
conversion of cholesterol to cholic acid
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
?
-
metabolism of cholesterol
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
?
-
mitochondrial cytochrome P450 forms a complex with the substrate
-
-
?
cholesterol + reduced adrenodoxin + O2
27-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
-
?
cholesterol + reduced adrenodoxin + O2
27-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
27-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
27-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
27-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
-
?
additional information
?
-
-
the regioselectivity of the reaction is determined by residues of the helix F loop, e.g. F207, I211, and F215, substrate regiospecificity of wild-type and mutant enzymes, overview, 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid and 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-27-al are poor substrates
-
-
?
additional information
?
-
-
CYP27A1 catalyzes sterol 27-hydroxylation in many extrahepatic tissues and metabolizes bile acid intermediates in the liver, and vitamin D3 in the kidney
-
-
?
additional information
?
-
human CYP27A1 catalyzes hydroxylation of beta-sitosterol and ergosterol, CYP27A1 catalyzes the 26-hydroxylation of cholesterol to form the physiologically active product 26-hydroxycholesterol. CYP27A1 is also able to accept other steroids with structural similarity to cholesterol as substrates such as vitamin D3 and its precursor 7-dehydrocholesterol. NMR spectroscopic product analysis
-
-
?
additional information
?
-
-
enzyme CYP125A4 also oxidizes cholesterol, although it has a much higher activity for the oxidation of 7alpha-hydroxycholesterol, EC 1.14.14.23. The enzyme forms 7alpha,26-dihydroxycholesterol
-
-
?
additional information
?
-
-
the enzyme catalyzes the first step in the oxidation of the side chain of sterol intermediates in the biosynthesis of bile acids
-
-
?
additional information
?
-
-
a multifunctional enzyme catalyzing also the reaction of 25-hydroxyvitamin D3 1alpha-hydroxylase, EC 1.14.13.13, as well as the 24- and 25-hydroxylation of cholesterol, the truncated enzyme form is less efficient than the full-length CYP27A in the 27-hydroxylation of C27-sterols, and much less efficient in the 25-hydroxylation of 1alpha-hydroxyvitamin D3
-
-
?
additional information
?
-
-
the enzyme does not perform 7alpha-, 12alpha-, or 25-hydroxylations on C27-steroids
-
-
?
additional information
?
-
-
the sterol 27-hydroxylase performs multiple monooxygenations in the conversion of 58-cholestane-3alpha,7alpha,12alpha-triol into 3alpha,7alpha,l2alpha-trihydroxy-5beta-cholestanoic acid, product identification by gas spectrometry
-
-
?
additional information
?
-
-
sterol 27-hydroxylase is regulated by liver X receptor signaling, overview
-
-
?
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(24S)-3beta-hydroxy-24-methyl-5alpha-cholesta-8(14),22-dien-15-one + reduced adrenodoxin + H+ + O2
?
-
the substrate is a potential drug for lowering cholesterol in the treatment and/or prevention of coronary artery disease, but it is rapidly metabolized in the liver
-
-
?
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,27-tetraol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid + oxidized adrenodoxin + H2O
-
-
-
-
?
3beta-hydroxy-5alpha-cholest-8(14)-en-15-one + reduced adrenodoxin + H+ + O2
?
-
the substrate is a potential drug for lowering cholesterol in the treatment and/or prevention of coronary artery disease, but it is rapidly metabolized in the liver
-
-
?
5-cholestene-3beta,7alpha-diol + reduced adrenodoxin + O2
5-cholestene-3alpha,7alpha,26-triol + oxidized adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + oxidized adrenodoxin + H2O
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + H+ + O2
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + oxidized adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + oxidized adrenodoxin + H2O
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid + oxidzed adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + oxidized adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
?
5beta-cholestane-3alpha,7alpha-diol + reduced adrenodoxin + O2
5beta-cholestane-3alpha,7alpha,26-triol + oxidized adrenodoxin + H2O
-
-
-
-
?
7alpha-hydroxy-4-cholesten-3-one + reduced adrenodoxin + O2
7alpha,26-dihydroxy-4-cholesten-3-one + oxidized adrenodoxin + H2O
-
-
-
-
?
cholesterol + reduced adrenodoxin + H+ + O2
26-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
-
?
cholesterol + reduced adrenodoxin + O2
27-hydroxycholesterol + oxidized adrenodoxin + H2O
additional information
?
-
5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + oxidized adrenodoxin + H2O
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + oxidized adrenodoxin + H2O
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + reduced adrenodoxin + O2
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + oxidized adrenodoxin + H2O
-
-
-
r
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + oxidized adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + oxidized adrenodoxin + H2O
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
?
-
-
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
?
-
conversion of cholesterol to cholic acid
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
?
-
metabolism of cholesterol
-
-
?
5beta-cholestane-3alpha,7alpha,12alpha-triol + reduced adrenodoxin + O2
?
-
mitochondrial cytochrome P450 forms a complex with the substrate
-
-
?
cholesterol + reduced adrenodoxin + O2
27-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
-
?
cholesterol + reduced adrenodoxin + O2
27-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
27-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
?
cholesterol + reduced adrenodoxin + O2
27-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
?
additional information
?
-
-
CYP27A1 catalyzes sterol 27-hydroxylation in many extrahepatic tissues and metabolizes bile acid intermediates in the liver, and vitamin D3 in the kidney
-
-
?
additional information
?
-
-
enzyme CYP125A4 also oxidizes cholesterol, although it has a much higher activity for the oxidation of 7alpha-hydroxycholesterol, EC 1.14.14.23. The enzyme forms 7alpha,26-dihydroxycholesterol
-
-
?
additional information
?
-
-
the enzyme catalyzes the first step in the oxidation of the side chain of sterol intermediates in the biosynthesis of bile acids
-
-
?
additional information
?
-
-
sterol 27-hydroxylase is regulated by liver X receptor signaling, overview
-
-
?
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malfunction
-
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
malfunction
CYP27A1 deficiency may upregulate the activity of 11beta-hydroxysteroid dehydrogenase 1, and downregulate the activity of 11beta-hydroxysteroid dehydrogenase 2. In a patient with cerebrotendinous xanthomatosis carrying a loss-of-function mutation in CYP27A1, the plasma concentrations of 27-hydroxycholesterol are dramatically reduced, with enhanced HSD11B1 and diminished HSD11B2 activities
malfunction
in Cyp27a1 knockout mice, the plasma concentrations of 27-hydroxycholesterol are undetectable. In the liver of the mutant mice, the increase in concentrations of active glucocorticoids is due to increased liver weight as a consequence of Cyp27a1 deficiency
malfunction
post-transcriptional silencing of the CYP27A1 gene in human trophoblast 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
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 is involved in cholesterol handling and metabolism
metabolism
the enzyme initiates the biosynthesis of bile acids, pathway overview
metabolism
the enzyme initiates the biosynthesis of bile acids, pathway overview
physiological function
-
CYP27 acts as a cholesterol efflux mediators
physiological function
-
CYP27A! catalyzes sterol 27-hydroxylation in many extrahepatic tissues and metabolizes bile acid intermediates in the liver, and vitamin D3 in the kidney
physiological function
-
pathophysiological role of CYP27A1 in the CNS
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
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
physiological function
CYP27A1, sterol 27-hydroxylase, catalyzes the oxidation of cholesterol to 27-hydroxycholesterol in the bile acid biosynthesis and participates in other processes of cholesterol homeostasis. CYP27A1 is also involved in metabolism of vitamin D as vitamin D hydroxylase
physiological function
in the liver, CYP27A1 catalyses the first step of the alternative pathway of bile acid biosynthesis and intermediate reactions in the classical pathway initiated by CYP7A1. In extrahepatic tissues, CYP27A1 plays a role in reverse cholesterol transport because its product 27-hydroxycholesterol is removed and carried to the liver, where it is converted to bile acids. 27-Hydroxycholesterol is a key regulator of cholesterol homeostasis. Sterol 27-hydroxylase (CYP27A1) catalyses the first step in the alternative pathway of bile acid synthesis by hydroxylating cholesterol to 27-hydroxycholesterol, which is a natural ligand for liver X receptor. In vitro agonist treatment of liver X receptor downregulates the activity of 11beta-hydroxysteroid dehydrogenase 1, HSD11B1, that is involved in regulation of intracellular availability of glucocorticoids
physiological function
in the liver, CYP27A1 catalyses the first step of the alternative pathway of bile acid biosynthesis and intermediate reactions in the classical pathway initiated by CYP7A1. In extrahepatic tissues, CYP27A1 plays a role in reverse cholesterol transport because its product 27-hydroxycholesterol is removed and carried to the liver, where it is converted to bile acids. 27-Hydroxycholesterol is a key regulator of cholesterol homeostasis. Sterol 27-hydroxylase (CYP27A1) catalyses the first step in the alternative pathway of bile acid synthesis by hydroxylating cholesterol to 27-hydroxycholesterol, which is a natural ligand for liver X receptor. In vitro agonist treatment of liver X receptor downregulates the activity of 11beta-hydroxysteroid dehydrogenase 1, HSD11B1, that is involved in regulation of intracellular availability of glucocorticoids
physiological function
the enzyme forms 26-hydroxycholesterolthat acts as an endogenous selective estrogen receptor modulator and has, among multiple other functions, a strong influence on the promotion of estrogen receptor dependent breast cancer, the bone mineralization as well as the cardiovascular system
physiological function
-
utilization of cholesterol is initiated by three cholesterol hydroxylases, CYP125A3, CYP142A2, and CYP125A4. A CYP125A3/CYP142A2 double knockout mutant of Mycobacterium smegmatis is still able to grow on cholesterol as sole carbom source, albeit at a slower rate than the wild-type
additional information
-
cerebrotendinous xanthomatosis, CTX, is a rare autosomal recessive sterol storage disease caused by a mutated sterol 27-hydroxylase CYP27A1 gene
additional information
-
mutations of gene CYP27A1 cause defects in the cholesterol pathway to bile acids that lead to the storage of cholestanol and cholesterol in tendons, lenses and the central nervous system. This disorder is the cause of a clinical syndrome known as cerebrotendinous xanthomatosis, CTX, phenotype, overview
additional information
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the rare disease cerebrotendinous xanthomatosis, CTX, is caused by a lack of CYP27A1 in humans, characterized by cholestanol-containing xanthomas in brain and tendons, but mice with the same defect do not develop xanthomas. Female cyp27a1 knockout mice have an increase of cholestanol of about 2.5fold in plasma, 6fold in tendons, and 12fold in brain. Treatment of cyp27a1-/- mice with 0.05% cholic acid normalizes the cholestanol levels in tendons and plasma and reduces the content in the brain. No significant difference between cyp27a1 knockout mice and wild-type mice with respect to content of cholesterol in the brain. 7alpha-Hydroxy-4-cholesten-3-one is an important precursor of cholestanol in the brain of the cyp27a1 knockoout mice
additional information
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the ability of CYP125A4 to oxidize 7alpha-hydroxycholesterol is due, at least in part, to the presence of a smaller amino acid side chain facing C-7 of the sterol substrate than in CYP125A3
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F207A/I211A/F215A
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site-directed mutagenesis, the mutant shows altered substrate regiospecificity compared to the wild-type enzyme
F207K
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site-directed mutagenesis, the mutant shows altered substrate regiospecificity compared to the wild-type enzyme
F207K/I211K/F215K
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site-directed mutagenesis, nearly no expression of the mutant in Escherichia coli
F215A
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site-directed mutagenesis, the mutant shows altered substrate regiospecificity compared to the wild-type enzyme
F215K
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site-directed mutagenesis, the mutant shows altered substrate regiospecificity compared to the wild-type enzyme
I211K
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site-directed mutagenesis, the mutant shows altered substrate regiospecificity compared to the wild-type enzyme
I211K/F215K
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site-directed mutagenesis, the mutant shows altered substrate regiospecificity compared to the wild-type enzyme
R104/R441QQ
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naturally occuring mutations, cause cerebrotendinous xanthomatosis
R441W
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naturally occuring mutation, involved in cerebrotendinous xanthomatosis
W235A
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site-directed mutagenesis, the mutant is partly expressed as cytosolic enzyme, the mutant shows altered substrate regiospecificity compared to the wild-type enzyme
Y238A
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site-directed mutagenesis, the mutant is partly expressed as cytosolic enzyme, the mutant shows altered substrate regiospecificity compared to the wild-type enzyme
R104/R441QQ
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naturally occuring mutations, cause cerebrotendinous xanthomatosis
R441W
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naturally occuring mutation, involved in cerebrotendinous xanthomatosis
additional information
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expression and subcellular distribution of the P450 27A1 mutants, overview
additional information
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naturally occuring mutations in the CYP27A1 gene cause cerebrotendinous xanthomatosis, CTX. A German patient is a compound heterozygote carrying two mutations both located in exon 8, phenotypes, overview. One mutation is a novel four nucleotide deletion, c.1330-1333delTTCC, that results in a frameshift and the occurrence of a premature stop codon leading to the formation of a truncated protein of 448 amino acids. The other mutation, previously reported, is a C - > T transition, c.c.1381C-T, that converts the glutamine codon at position 461 into a termination codon, p.Q461X
additional information
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naturally occuring mutations in the CYP27A1 gene cause cerebrotendinous xanthomatosis, CTX. One of two Japanese patients is a compound heterozygote for Arg104Gln in exon 2 and Arg441Gln in exon 8, the other patient is a compound heterozygote for Arg441Trp in exon 8 and a second mutation not identified
additional information
silencing of gene CYP27A1 by targeting siRNA
additional information
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naturally occuring mutations in the CYP27A1 gene cause cerebrotendinous xanthomatosis, CTX. One of two Japanese patients is a compound heterozygote for Arg104Gln in exon 2 and Arg441Gln in exon 8, the other patient is a compound heterozygote for Arg441Trp in exon 8 and a second mutation not identified
additional information
construction of enzyme knockout null mutant mice
additional information
silencing of gene CYP27A1 by targeting siRNA
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