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cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
cholesterol + [reduced NADPH-hemoprotein reductase] + O2
(24S)-cholest-5-ene-3beta,24-diol + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
?
cholesterol + NADPH + O2
(24S)-hydroxycholesterol + NADP+ + H2O
cholesterol + reduced adrenodoxin + O2
24-hydroxycholesterol + oxidized adrenodoxin + H2O
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
additional information
?
-
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
?
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
24-hydroxylation represents an important pathway by which cholesterol is secreted from the brain. The enzyme contributes little to overall bile acid synthesis but is important in the turnover of cholesterol in the brain
-
-
?
cholesterol + NADPH + O2
(24S)-hydroxycholesterol + NADP+ + H2O
-
-
-
-
?
cholesterol + NADPH + O2
(24S)-hydroxycholesterol + NADP+ + H2O
-
the enzyme is important in cholesterol metabolism in the brain, cholesterol dynamics in the fetal and neonatal brain, overview
the product is able to travers the blood-brain barrier, while the substrate is not, transport, and excretion of (24S)-hydroxycholesterol, oxycholesterol transport mechanisms, overview
-
?
cholesterol + reduced adrenodoxin + O2
24-hydroxycholesterol + oxidized adrenodoxin + H2O
-
-
-
-
?
cholesterol + reduced adrenodoxin + O2
24-hydroxycholesterol + oxidized adrenodoxin + H2O
-
enzyme deficiency leads to a suppression of the mevalonate pathway and a defect in learning
-
-
?
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
-
?
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
-
cholesterol 24-hydroxylase constitutes a major tissue-specific pathway for cholesterol turnover in the brain
-
-
?
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
-
the enzyme is required for learning and memory formation, mice deficient in CYP46A1 exhibit impaired learning and defective hippocampal long-term potentiation, overview
-
-
?
additional information
?
-
the enzyme is a mediator of cholesterol homeostasis in the brain
-
-
?
additional information
?
-
-
the enzyme is a mediator of cholesterol homeostasis in the brain
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
24-hydroxylation represents an important pathway by which cholesterol is secreted from the brain. The enzyme contributes little to overall bile acid synthesis but is important in the turnover of cholesterol in the brain
-
-
?
cholesterol + [reduced NADPH-hemoprotein reductase] + O2
(24S)-cholest-5-ene-3beta,24-diol + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
?
cholesterol + NADPH + O2
(24S)-hydroxycholesterol + NADP+ + H2O
-
the enzyme is important in cholesterol metabolism in the brain, cholesterol dynamics in the fetal and neonatal brain, overview
the product is able to travers the blood-brain barrier, while the substrate is not, transport, and excretion of (24S)-hydroxycholesterol, oxycholesterol transport mechanisms, overview
-
?
cholesterol + reduced adrenodoxin + O2
24-hydroxycholesterol + oxidized adrenodoxin + H2O
-
enzyme deficiency leads to a suppression of the mevalonate pathway and a defect in learning
-
-
?
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
additional information
?
-
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
-
cholesterol 24-hydroxylase constitutes a major tissue-specific pathway for cholesterol turnover in the brain
-
-
?
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
-
the enzyme is required for learning and memory formation, mice deficient in CYP46A1 exhibit impaired learning and defective hippocampal long-term potentiation, overview
-
-
?
additional information
?
-
the enzyme is a mediator of cholesterol homeostasis in the brain
-
-
?
additional information
?
-
-
the enzyme is a mediator of cholesterol homeostasis in the brain
-
-
?
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malfunction
knocking down CYP46A1 expression in the striatum, via an adeno-associated virus-mediated delivery of selective shCYP46A1, reproduced the Huntingtons disease phenotype, with spontaneous striatal neuron degeneration and motor deficits. CYP46A1 expression levels are reduced in Huntington's disease. In the R6/2 Huntington's disease mouse model, adeno-associated virus-mediated delivery of CYP46A1 into the striatum decreases neuronal atrophy, decreases the number, intensity level and size of expansion in huntingtin aggregates and improves motor deficits, as assessed by rotarod and clasping behavioural tests. Adeno-associated virus-CYP46A1 infection in R6/2 mice also restores levels of cholesterol and lanosterol and increases levels of desmosterol
physiological function
cholesterol 24-hydroxylase is the neuronal-specific and rate-limiting enzyme for cholesterol conversion to 24S-hydroxycholesterol, regulation of cholesterol homeostasis by CYP46A1. In vitro, CYP46A1 restoration protects SThdhQ111 and Exp-HTT-expressing striatal neurons in culture from cell death
malfunction
-
disruption of the cholesterol 24-hydroxylase gene causes an 50% decrease in cholesterol turnover, which is compensated for by an equal decrease in the rate of de novo cholesterol synthesis. Mice lacking cholesterol 24-hydroxylase show that whole-body fatty acid and cholesterol metabolism are normal. Profound learning disabilities in cholesterol 24-hydroxylase-deficient mice are often caused by gross anatomical defects in the subregions of the brain implicated in the behavior. A minimal concentration of 0.2 mM geranylgeraniol is required to restore LTP in hippocampal slices from knockout mice
physiological function
-
amyloid precursor protein expression and amyloid plaque deposition in the cortex and hippocampus of male and female Alzheimer's disease mice between the ages of 3 to 15 months are similar in the presence and absence of cholesterol 24-hydroxylase. Loss of one or both cholesterol 24-hydroxylase alleles increases longevity in Alzheimers disease mice. Cholesterol synthetic rates are reduced in animals lacking 24-hydroxylase, and this reduction is specific to cholesterol
physiological function
-
cholesterol 24-hydroxylase regulates TrkB activity in mature hippocampal neurons
physiological function
-
overexpression of human CYP46A1 gene does not modify the expression of endogenous murine Cyp46A1 gene
physiological function
-
the capacity to turn over cholesterol via the cholesterol 24-hydroxylase pathway may be acquired early during development of the central nervous system. The enzyme reduces the excretion of sterols from the brain but does not abolish this removal process
physiological function
-
visual disturbances in CYP46A1 gene knockout mice
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additional information
knocking down CYP46A1 expression in the striatum, via an adeno-associated virus-mediated delivery of selective shCYP46A1. Expression of shRNA sequence that inhibits CYP46A1 expression in vitro and in vivo, phenotype, overview. CYP46A1 restoration in the striatum improves the motor phenotype of R6/2 mice
additional information
-
knocking down CYP46A1 expression in the striatum, via an adeno-associated virus-mediated delivery of selective shCYP46A1. Expression of shRNA sequence that inhibits CYP46A1 expression in vitro and in vivo, phenotype, overview. CYP46A1 restoration in the striatum improves the motor phenotype of R6/2 mice
additional information
-
brains from mice lacking 24-hydroxylase excrete cholesterol more slowly, and the tissue compensates by suppressing the mevalonate pathway, this suppression causes a defect in learning, 24-hydroxylase knockout mice exhibit severe deficiencies in spatial, associative, and motor learning, and in hippocampal long-term potentiation, the effects of genetic elimination of 24-hydroxylase on long-term potentiation are reversed by a 20-min treatment with geranylgeraniol but not by cholesterol, phenotype, overview
additional information
-
construction of knockout mice, concentration and the pool of cholesterol in the CNS is unchanged compared with control animals, but synthesis is suppressed by about 25% in the CYP46a1-deficient mice, but not in those lacking 7a- or 27-hydroxylase activity, the concentrations of 24S-hydroxycholesterol in the brain and plasma decline to very low levels, the CNS in the mouse apparently responds appropriately to loss of this excretory pathway by suppressing endogenous synthesis by an amount exactly equal to the mass of cholesterol that would normally be excreted as 24S-hydroxycholesterol
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Russell, D.W.
Oxysterol biosynthetic enzymes
Biochim. Biophys. Acta
1529
126-135
2000
Mus musculus (Q9WVK8), Homo sapiens (Q9Y6A2)
brenda
Lund, E.G.; Xie, C.; Kotti, T.; Turley, S.D.; Dietschy, J.M.; Russell, D.W.
Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover
J. Biol. Chem.
278
22980-22988
2003
Mus musculus
brenda
Lund, E.G.; Guileyardo, J.M.; Russell, D.W.
cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain
Proc. Natl. Acad. Sci. USA
96
7238-7243
1999
Homo sapiens (Q9Y6A2), Homo sapiens, Mus musculus (Q9WVK8), Mus musculus
brenda
Luetjohann, D.
Cholesterol metabolism in the brain: importance of 24S-hydroxylation
Acta Neurol. Scand.
114 (Suppl. 185)
33-42
2006
Homo sapiens, Mus musculus, Sus scrofa
brenda
Kotti, T.J.; Ramirez, D.M.; Pfeiffer, B.E.; Huber, K.M.; Russell, D.W.
Brain cholesterol turnover required for geranylgeraniol production and learning in mice
Proc. Natl. Acad. Sci. USA
103
3869-3874
2006
Mus musculus
brenda
Ramirez, D.M.; Andersson, S.; Russell, D.W.
Neuronal expression and subcellular localization of cholesterol 24-hydroxylase in the mouse brain
J. Comp. Neurol.
507
1676-1693
2008
Mus musculus
brenda
Russell, D.W.; Halford, R.W.; Ramirez, D.M.; Shah, R.; Kotti, T.
Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain
Annu. Rev. Biochem.
78
1017-1040
2009
Bos taurus, Canis lupus familiaris, Cavia porcellus, Danio rerio (A5WWJ0), Equus caballus, Equus sp., Gallus gallus, Homo sapiens, Macaca mulatta, Mus musculus, Ornithorhynchus anatinus, Oryctolagus cuniculus, Pan troglodytes, Rattus norvegicus, Xenopus laevis (Q7SYY2)
brenda
Shafaati, M.; O'Driscoll, R.; Bjoerkhem, I.; Meaney, S.
Transcriptional regulation of cholesterol 24-hydroxylase by histone deacetylase inhibitors
Biochem. Biophys. Res. Commun.
378
689-694
2009
Homo sapiens, Mus musculus, Mus musculus C57B6-J
brenda
Shafaati, M.; Mast, N.; Beck, O.; Nayef, R.; Heo, G.Y.; Bjoerkhem-Bergman, L.; Lutjohann, D.; Bjoerkhem, I.; Pikuleva, I.A.
The antifungal drug voriconazole is an efficient inhibitor of brain cholesterol 24S-hydroxylase (CYP46A1) in vitro and in vivo
J. Lipid Res.
51
318-323
2010
Homo sapiens, Mus musculus
brenda
Martin, M.G.; Perga, S.; Trovo, L.; Rasola, A.; Holm, P.; Rantamaeki, T.; Harkany, T.; Castren, E.; Chiara, F.; Dotti, C.G.
Cholesterol loss enhances TrkB signaling in hippocampal neurons aging in vitro
Mol. Biol. Cell
19
2101-2112
2008
Mus musculus, Rattus norvegicus
brenda
Hudry, E.; Van Dam, D.; Kulik, W.; De Deyn, P.P.; Stet, F.S.; Ahouansou, O.; Benraiss, A.; Delacourte, A.; Bougneres, P.; Aubourg, P.; Cartier, N.
Adeno-associated Virus gene therapy with cholesterol 24-hydroxylase reduces the amyloid pathology before or after the onset of amyloid plaques in mouse models of Alzheimers disease
Mol. Ther.
18
44-53
2010
Homo sapiens, Mus musculus, Mus musculus APP23
brenda
Halford, R.W.; Russell, D.W.
Reduction of cholesterol synthesis in the mouse brain does not affect amyloid formation in Alzheimers disease, but does extend lifespan
Proc. Natl. Acad. Sci. USA
106
3502-3506
2009
Mus musculus
brenda
Boussicault, L.; Alves, S.; Lamaziere, A.; Planques, A.; Heck, N.; Moumne, L.; Despres, G.; Bolte, S.; Hu, A.; Pages, C.; Galvan, L.; Piguet, F.; Aubourg, P.; Cartier, N.; Caboche, J.; Betuing, S.
CYP46A1, the rate-limiting enzyme for cholesterol degradation, is neuroprotective in Huntingtons disease
Brain
139
953-970
2016
Homo sapiens (Q9Y6A2), Homo sapiens, Mus musculus (Q9WVK8), Mus musculus, Mus musculus C57BL/6 (Q9WVK8)
brenda