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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
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
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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
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CYP27 acts as a cholesterol efflux mediators
physiological function
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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
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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
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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
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cerebrotendinous xanthomatosis, CTX, is a rare autosomal recessive sterol storage disease caused by a mutated sterol 27-hydroxylase CYP27A1 gene
additional information
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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