1.14.14.25: cholesterol 24-hydroxylase

This is an abbreviated version!
For detailed information about cholesterol 24-hydroxylase, go to the full flat file.

Reaction

Synonyms

24S-hydroxylase, CH24H, cholesterol 24-hydroxylase, cholesterol 24-monooxygenase, cholesterol 24S hydroxylase, cholesterol 24S-hydroxylase, cholesterol hydroxylase, cholesterol-24S-hydroxylase, CYP46, CYP46A, CYP46A1, cytochrome P-450 46A1, cytochrome P450 46A1, cytochrome P450 cholesterol 24-hydroxylase, EC 1.14.13.98

ECTree

     1 Oxidoreductases

         1.14 Acting on paired donors, with incorporation or reduction of molecular oxygen

             1.14.14 With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor

                1.14.14.25 cholesterol 24-hydroxylase

Advanced search results

Do not include text mining results

Include results (more...)

Include results (more...)

Results	in table
5	Activating Compound
14	AA Sequence
6	Application
2	CAS Registry Number
25	Cloned(Commentary)
49	Cofactor
2	Crystallization (Commentary)
350	Disease/ Diagnostics
11	Expression
32	General Information
19	Inhibitors
1	Ki Value [mM]
10	KM Value [mM]
20	Localization
2	Metals/Ions
5	Molecular Weight [Da]
33	Natural Substrates/ Products (Substrates)
235	Organism
1	Pathway
6	PDB ID
2	pH Optimum
16	Protein Variants
5	Purification (Commentary)
2	Reaction
3	Reaction Type
68	Reference
132	Source Tissue
77	Substrates and Products (Substrate)
5	Subunits
88	Synonyms
1	Systematic Name
1	Temperature Optimum [°C]
9	Turnover Number [1/s]

Substrates Products

print visible entries

print all entries

Substrates Products on EC 1.14.14.25 - cholesterol 24-hydroxylase

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.

top print hide show all columns Go to Substrate/Product Search

Please wait a moment until the data is sorted. This message will disappear when the data is sorted.

SUBSTRATE

PRODUCT                       

REACTION DIAGRAM

ORGANISM

UNIPROT

COMMENTARY
(Substrate)

LITERATURE
(Substrate)

COMMENTARY
(Product)

LITERATURE
(Product)

Reversibility
r=reversible
ir=irreversible
?=not specified

(24S)-24-hydroxycholesterol + [reduced NADPH-hemoprotein reductase] + O2

24,25-dihydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Homo sapiens

-

-

657671, 657971

-

-

?

(24S)-24-hydroxycholesterol + [reduced NADPH-hemoprotein reductase] + O2

24,27-dihydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Homo sapiens

-

-

657671, 657971

-

-

?

(24S)-hydroxycholesterol + [reduced NADPH-hemoprotein reductase] + O2

24,25-dihydroxycholesterol + 24,27-dihydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Homo sapiens

-

preferred substrate in vitro

673298

-

-

?

cholesterol + NADPH + O2

(24S)-hydroxycholesterol + NADP+ + H2O

7 entries

cholesterol + reduced adrenodoxin + O2

24-hydroxycholesterol + oxidized adrenodoxin + H2O

3 entries

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

23 entries

cholesterol + [reduced NADPH-hemoprotein reductase] + O2

(24S)-cholest-5-ene-3beta,24-diol + [oxidized NADPH-hemoprotein reductase] + H2O

5 entries

cholesterol 3-sulfate + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol 3-sulfate + [oxidized NADPH-hemoprotein reductase] + H2O

Homo sapiens

Q9Y6A2

-

689814

-

-

?

dextromethorphan + [reduced NADPH-hemoprotein reductase] + O2

?

Homo sapiens

-

O- and N-demethylation

673298

-

-

?

diclofenac + [reduced NADPH-hemoprotein reductase] + O2

?

Homo sapiens

-

4'-hydroxylation

673298

-

-

?

phenacetin + [reduced NADPH-hemoprotein reductase] + O2

?

Homo sapiens

-

O-deethylation

673298

-

-

?

additional information

?

-

13 entries

cholesterol + NADPH + O2

(24S)-hydroxycholesterol + NADP+ + H2O

Homo sapiens

-

-

671173, 673298

-

-

?

cholesterol + NADPH + O2

(24S)-hydroxycholesterol + NADP+ + H2O

Homo sapiens

-

the enzyme is important in cholesterol metabolism in the brain, overview

671173

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 + NADPH + O2

(24S)-hydroxycholesterol + NADP+ + H2O

Homo sapiens

-

the enzyme is responsible for cholesterol elimination from brain, (24S)-hydroxycholesterol can cross the blood-brain barrier, enter the circulation, and then be delivered to the liver for further degradation, cholesterol metabolism, overview, CYP46A1 may participate in metabolism of neurosteroids and drugs that are targeted to the central nervous system

673298

-

-

?

cholesterol + NADPH + O2

(24S)-hydroxycholesterol + NADP+ + H2O

Mus musculus

-

-

671173

-

-

?

cholesterol + NADPH + O2

(24S)-hydroxycholesterol + NADP+ + H2O

Mus musculus

-

the enzyme is important in cholesterol metabolism in the brain, cholesterol dynamics in the fetal and neonatal brain, overview

671173

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 + NADPH + O2

(24S)-hydroxycholesterol + NADP+ + H2O

Sus scrofa

-

-

671173

-

-

?

cholesterol + NADPH + O2

(24S)-hydroxycholesterol + NADP+ + H2O

Sus scrofa

-

the enzyme is important in cholesterol metabolism in the brain, overview

671173

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

Mus musculus

-

-

676852

-

-

?

cholesterol + reduced adrenodoxin + O2

24-hydroxycholesterol + oxidized adrenodoxin + H2O

Mus musculus

-

enzyme deficiency leads to a suppression of the mevalonate pathway and a defect in learning

676852

-

-

?

cholesterol + reduced adrenodoxin + O2

24-hydroxycholesterol + oxidized adrenodoxin + H2O

Rattus norvegicus

-

-

675535

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Bos taurus

-

-

686258, 701715

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Bos taurus

-

the enzyme is important in cholesterol homeostasis in cerebral structures, CYP46A1 might be involved in retinal pathologies like age-related macular degeneration or glaucomas, overview

686258

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Cavia porcellus

-

-

701715

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Equus caballus

-

-

701715

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Homo sapiens

-

-

657671, 657971, 684856, 701715, 705008, 705825, 705920, 711641, 712869

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Homo sapiens

Q9Y6A2

-

712869

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Homo sapiens

-

-

727298, 728617

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Homo sapiens

Q9Y6A2

-

658159

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Homo sapiens

Q9Y6A2

-

689814

-

-

r

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Homo sapiens

Q9Y6A2

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

658159

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Homo sapiens

-

initiates cholesterol degradation in the brain. In addition to the involvement in cholesterol homeostasis in the brain, this enzyme may participate in metabolism of neurosteroids and drugs that can cross the blood-brain barrier and are targeted to the central nervous system

657971

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Homo sapiens

-

a major pathway for excretion of excess cholesterol from the brain, polymorphisms within the CYP46A1 gene are associated with Alzheimer’s disease incidence. The ratio between 24S-OHC and 27-OHC is of importance for the generation of amyloid in the brain, overview

684856

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Homo sapiens

Q9Y6A2

cholesterol enters the enzyme through the membrane. In CYP46A1, the three putative membrane-interacting peptides in the soluble domain, 59V-K69, 77V-K94, and 217L-K231, form the entrance to the substrate access channel and represent the secondary structural elements (the A helix and beta1 sheet and F-G loop regions)

695874

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Mus musculus

-

-

659216, 687987, 701715, 705008, 705825, 706536

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Mus musculus

Q9WVK8

-

658159

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Mus musculus

Q9WVK8

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

658159

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Mus musculus

-

cholesterol 24-hydroxylase constitutes a major tissue-specific pathway for cholesterol turnover in the brain

659216

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Mus musculus

-

the enzyme is required for learning and memory formation, mice deficient in CYP46A1 exhibit impaired learning and defective hippocampal long-term potentiation, overview

687987

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Mus musculus APP23

-

-

705825

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Oryctolagus cuniculus

-

-

701715

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Rattus norvegicus

-

-

686258, 688555, 701715

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Rattus norvegicus

-

24-hydroxycholesterol induces, through the liver X receptor, activation of genes involved in cholesterol efflux, including the ATP-binding cassette transporter A1 and apolipoprotein E, overview

688555

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2

(24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O

Rattus norvegicus

-

the enzyme is important in cholesterol homeostasis in cerebral structures, CYP46A1 might be involved in retinal pathologies like age-related macular degeneration or glaucomas, overview

686258

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + O2

(24S)-cholest-5-ene-3beta,24-diol + [oxidized NADPH-hemoprotein reductase] + H2O

Homo sapiens

Q9Y6A2

-

735877, 736072, 736502

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + O2

(24S)-cholest-5-ene-3beta,24-diol + [oxidized NADPH-hemoprotein reductase] + H2O

Mus musculus

Q9WVK8

-

735877

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + O2

(24S)-cholest-5-ene-3beta,24-diol + [oxidized NADPH-hemoprotein reductase] + H2O

Mus musculus C57BL/6

Q9WVK8

-

735877

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + O2

(24S)-cholest-5-ene-3beta,24-diol + [oxidized NADPH-hemoprotein reductase] + H2O

Rattus norvegicus

F7EN52

-

735602

-

-

?

cholesterol + [reduced NADPH-hemoprotein reductase] + O2

(24S)-cholest-5-ene-3beta,24-diol + [oxidized NADPH-hemoprotein reductase] + H2O

Rattus norvegicus Wistar

F7EN52

-

735602

-

-

?

additional information

?

-

Homo sapiens

-

CYP46A1 affects the pathophysiology of Alzheimers' disease and provides insight into how polymorphisms in the CYP46A1 gene might influence the pathophysiology of this prevalent disease

659374

-

-

?

additional information

?

-

Homo sapiens

-

regulation of cholesterol synthesis is more important for maintenance of cholesterol homeostasis in brain than is the corresponding regulation of cholesterol removal

659516

-

-

?

additional information

?

-

Homo sapiens

Q9Y6A2

the enzyme is a mediator of cholesterol homeostasis in the brain

660401

-

-

?

additional information

?

-

Homo sapiens

-

the enzyme is a mediator of cholesterol homeostasis in the brain

660401

-

-

?

additional information

?

-

Homo sapiens

-

the enzyme is able to carry out side chain hydroxylations of two endogenous C27-steroids with and without a double bond between C5-C6 (7R-hydroxycholesterol and cholestanol, respectively) and introduce a hydroxyl group on the steroid nucleus of the C21-steroid hormones with the C4-C5 double bond (progesterone and testosterone). P450 46A1 metabolizes xenobiotics carrying out dextromethorphan O-demethylation and N-demethylations, diclofenac 4'-hydroxylation, and phenacetin O-deethylation

657971

-

-

?

additional information

?

-

Homo sapiens

-

(24S)-hydroxycholesterol is a potent activator of the LXR receptor, CYP46A1-deficiency plays a role in the pathogenesis of this neurological disorder, such as Alzheimer's disease

673298

-

-

?

additional information

?

-

Homo sapiens

-

cholesterol metabolism is important in Alzheimer's disease pathogenesis, the enzyme is a risk factor for Alzheimer's disease, along with cholesterol 25-hydroxylase and ATP-binding cassette transporter A1, overview

660012

-

-

?

additional information

?

-

Homo sapiens

-

CYP46A1 shows broad substrate specificity

673298

-

-

?

additional information

?

-

Homo sapiens

-

(24S)-24-hydroxycholesterol activates alpha- and beta-secretases, while (27S)-27-hydroxycholesterol inhibits them, overview

684856

-

-

?

additional information

?

-

Homo sapiens

Q9Y6A2

active site structure and substrate binding, overview

689814

-

-

?

additional information

?

-

Homo sapiens

Q9Y6A2

coupled assay with recombinant Rattus norvegicus NADPH cytochrome P450 oxidoreductase

736502

-

-

?

additional information

?

-

Mus musculus

Q9WVK8

the enzyme is a mediator of cholesterol homeostasis in the brain

660401

-

-

?

additional information

?

-

Mus musculus

-

the enzyme is a mediator of cholesterol homeostasis in the brain

660401

-

-

?