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corticosterone 18-monooxygenase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: corticosterone + reduced adrenal ferredoxin + O2 = 18-hydroxycorticosterone + oxidized adrenal ferredoxin + H2O. [EC:1.14.15.5]

Corticosterone 18-monooxygenase activity refers to the enzymatic process that catalyzes the hydroxylation of corticosterone at the 18-position. This reaction introduces a hydroxyl group (OH) at the 18th carbon atom of the corticosterone molecule. The enzyme responsible for this activity is known as cytochrome P450 18A1 (CYP18A1).

This enzymatic reaction is a critical step in the biosynthesis of aldosterone, a mineralocorticoid hormone that plays a crucial role in regulating electrolyte balance and blood pressure. Aldosterone production occurs in the adrenal glands, specifically in the zona glomerulosa cells.

The hydroxylation of corticosterone by CYP18A1 is a complex process that involves the transfer of an oxygen atom from molecular oxygen (O2) to the substrate (corticosterone). This reaction requires the presence of NADPH (nicotinamide adenine dinucleotide phosphate) as a reducing agent and molecular oxygen as an oxidant.

The following steps are involved in the enzymatic reaction:

1. Binding of corticosterone and NADPH to the active site of CYP18A1.
2. Activation of molecular oxygen by CYP18A1, leading to the formation of a reactive oxygen species.
3. Transfer of an oxygen atom from the activated oxygen species to the 18th carbon atom of corticosterone, resulting in the formation of 18-hydroxycorticosterone.
4. Release of 18-hydroxycorticosterone and the oxidized form of NADPH from the enzyme.

The activity of CYP18A1 is tightly regulated by various factors, including:

* **Hormonal stimulation:** Angiotensin II, a potent vasoconstrictor and regulator of blood pressure, stimulates aldosterone production by activating CYP18A1.
* **Ionic changes:** High levels of potassium ions (K+) in the blood also stimulate aldosterone synthesis.
* **Other factors:** Factors such as stress, low blood pressure, and low blood volume can also influence CYP18A1 activity.

In summary, corticosterone 18-monooxygenase activity is a crucial enzymatic process that catalyzes the hydroxylation of corticosterone to form 18-hydroxycorticosterone, a key precursor for aldosterone biosynthesis. This reaction is tightly regulated by various hormonal and ionic signals and plays a vital role in maintaining electrolyte balance and blood pressure.'
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Proteins (2)

ProteinDefinitionTaxonomy
Cytochrome P450 11B2, mitochondrialA cytochrome P450 11B that is a translation product of the CYP11B2 gene in human. [PRO:DNx, UniProtKB:P19099]Homo sapiens (human)
Cytochrome P450 11B1, mitochondrialA cytochrome P450 11B that is a translation product of the CYP11B1 gene in human. [PRO:DNx, UniProtKB:P15538]Homo sapiens (human)

Compounds (18)

CompoundDefinitionClassesRoles
fluconazolefluconazole : A member of the class of triazoles that is propan-2-ol substituted at position 1 and 3 by 1H-1,2,4-triazol-1-yl groups and at position 2 by a 2,4-difluorophenyl group. It is an antifungal drug used for the treatment of mucosal candidiasis and for systemic infections including systemic candidiasis, coccidioidomycosis, and cryptococcosis.

Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal CANDIDIASIS and cryptococcal MENINGITIS in AIDS.
conazole antifungal drug;
difluorobenzene;
tertiary alcohol;
triazole antifungal drug
environmental contaminant;
P450 inhibitor;
xenobiotic
ketoconazole1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine : A dioxolane that is 1,3-dioxolane which is substituted at positions 2, 2, and 4 by imidazol-1-ylmethyl, 2,4-dichlorophenyl, and [para-(4-acetylpiperazin-1-yl)phenoxy]methyl groups, respectively.dichlorobenzene;
dioxolane;
ether;
imidazoles;
N-acylpiperazine;
N-arylpiperazine
letrozolenitrile;
triazoles
antineoplastic agent;
EC 1.14.14.14 (aromatase) inhibitor
metyraponemetyrapone : An aromatic ketone that is 3,3-dimethylbutan-2-one in which the methyl groups at positions 1 and 4 are replaced by pyridin-3-yl groups. A steroid 11beta-monooxygenase (EC 1.14.15.4) inhibitor, it is used in the diagnosis of adrenal insufficiency.

Metyrapone: An inhibitor of the enzyme STEROID 11-BETA-MONOOXYGENASE. It is used as a test of the feedback hypothalamic-pituitary mechanism in the diagnosis of CUSHING SYNDROME.
aromatic ketoneantimetabolite;
diagnostic agent;
EC 1.14.15.4 (steroid 11beta-monooxygenase) inhibitor
staurosporineindolocarbazole alkaloid;
organic heterooctacyclic compound
apoptosis inducer;
bacterial metabolite;
EC 2.7.11.13 (protein kinase C) inhibitor;
geroprotector
fadrozoleFadrozole: A selective aromatase inhibitor effective in the treatment of estrogen-dependent disease including breast cancer.imidazopyridine
azalanstatazalanstat: inhibits lanosterol 14 alpha-demethylase, the enzyme which catalyzes the first step in conversion of lanosterol to cholesterol in mammals; structure given in first source
1-benzylimidazole1-benzylimidazole: inhibits human thromboxane synthetase
abiraterone3beta-hydroxy-Delta(5)-steroid;
3beta-sterol;
pyridines
antineoplastic agent;
EC 1.14.99.9 (steroid 17alpha-monooxygenase) inhibitor
ketoconazole(2R,4S)-ketoconazole : A cis-1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine which dioxolane moiety has (2R,4S)-configuration.cis-1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine
posaconazolearomatic ether;
conazole antifungal drug;
N-arylpiperazine;
organofluorine compound;
oxolanes;
triazole antifungal drug;
triazoles
trypanocidal drug
1-(phenylmethyl)benzimidazolebenzimidazoles
etomidateetomidate : The ethyl ester of 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. It is an intravenous general anaesthetic with no analgesic activity.

Etomidate: Imidazole derivative anesthetic and hypnotic with little effect on blood gases, ventilation, or the cardiovascular system. It has been proposed as an induction anesthetic.
ethyl ester;
imidazoles
intravenous anaesthetic;
sedative
1-[(3-methylphenyl)methyl]benzimidazolebenzimidazoles
4-fluoro-N-(3-pyridinyl)benzamidecarbonyl compound;
organohalogen compound
4-(1H-imidazol-1-ylmethyl)benzonitrilebenzenes;
nitrile
vorozolevorozole: structure given in first source; vorozole/R 83842 is ((+)/dextro-isomer), RN 129731-10-8; R 83839 ((-)/levo-isomer)benzotriazoles
osilodrostatOsilodrostat: an orally active aldosterone-synthase inhibitor