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Literature summary extracted from

  • Pikuleva, I.A.
    Cholesterol-metabolizing cytochromes P450 (2006), Drug Metab. Dispos., 34, 513-520.
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.14.14.25 expression in Escherichia coli Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
1.14.15.6 additional information mutation of a cysteine residue in the F-G loop leads to altered membrane interaction and activity Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.14.14.25 0.0053
-
 cholesterol
-
 Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.14.14.25 endoplasmic reticulum
-
 Homo sapiens 5783
-
1.14.15.6 mitochondrial inner membrane membrane topology, overview Homo sapiens 5743
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.14.25 cholesterol + NADPH + O2 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 (24S)-hydroxycholesterol + NADP+ + H2O
-
 ?
1.14.14.25 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 ?
-
 ?
1.14.15.6 cholesterol + reduced ferredoxin + O2 Homo sapiens the catalyzed reaction is not the rate-limiting step in steroidogenesis except in placenta which lacks the steroidogenic acute regulatory protein, overview, enzyme deficiency by mutations leads to severe disorders, overview pregnenolone + 4-methylpentanal + oxidized ferredoxin
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.14.14.25 Homo sapiens
-
-
-
1.14.15.6 Homo sapiens
-
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
1.14.14.25 cholesterol + [reduced NADPH-hemoprotein reductase] + O2 = (24S)-cholest-5-ene-3beta,24-diol + [oxidized NADPH-hemoprotein reductase] + H2O structure-function relationship Homo sapiens
a

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.14.14.25 brain specific Homo sapiens
-
1.14.15.6 adrenal gland
-
 Homo sapiens
-
1.14.15.6 brain
-
 Homo sapiens
-
1.14.15.6 additional information the enzyme is expressed mainly in steroidogenic tissue Homo sapiens
-
1.14.15.6 ovary
-
 Homo sapiens
-
1.14.15.6 placenta
-
 Homo sapiens
-
1.14.15.6 testis
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.14.25 (24S)-hydroxycholesterol + [reduced NADPH-hemoprotein reductase] + O2 preferred substrate in vitro Homo sapiens 24,25-dihydroxycholesterol + 24,27-dihydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.25 cholesterol + NADPH + O2
-
 Homo sapiens (24S)-hydroxycholesterol + NADP+ + H2O
-
 ?
1.14.14.25 cholesterol + NADPH + O2 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 Homo sapiens (24S)-hydroxycholesterol + NADP+ + H2O
-
 ?
1.14.14.25 dextromethorphan + [reduced NADPH-hemoprotein reductase] + O2 O- and N-demethylation Homo sapiens ?
-
 ?
1.14.14.25 diclofenac + [reduced NADPH-hemoprotein reductase] + O2 4'-hydroxylation Homo sapiens ?
-
 ?
1.14.14.25 additional information (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 Homo sapiens ?
-
 ?
1.14.14.25 additional information CYP46A1 shows broad substrate specificity Homo sapiens ?
-
 ?
1.14.14.25 phenacetin + [reduced NADPH-hemoprotein reductase] + O2 O-deethylation Homo sapiens ?
-
 ?
1.14.15.6 cholesterol + reduced ferredoxin + O2 the catalyzed reaction is not the rate-limiting step in steroidogenesis except in placenta which lacks the steroidogenic acute regulatory protein, overview, enzyme deficiency by mutations leads to severe disorders, overview Homo sapiens pregnenolone + 4-methylpentanal + oxidized ferredoxin
-
 ?
1.14.15.6 cholesterol + reduced ferredoxin + O2 the enzyme is a cytochrome P450 enzyme, the enzyme structure possesses a substrate access channel, which is responsible for regioselectivity of the enzyme together with residue F202 Homo sapiens pregnenolone + 4-methylpentanal + oxidized ferredoxin
-
 ?

Subunits

EC Number Subunits Comment Organism
1.14.14.25 More structure-function relationship Homo sapiens
1.14.15.6 More the enzyme structure possesses a substrate access channel, the F-G loop is a membrane-interacting area Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
1.14.14.25 CYP46A1
-
 Homo sapiens
1.14.15.6 CYP11A1
-
 Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.14.14.25 0.11
-
 cholesterol
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.14.14.25 NADPH
-
 Homo sapiens
1.14.15.6 Ferredoxin
-
 Homo sapiens
1.14.15.6 Iron the enzyme is a cytochrome P450 enzyme Homo sapiens