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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Protein | Definition | Taxonomy |
---|---|---|
Cytochrome P450 11B2, mitochondrial | A cytochrome P450 11B that is a translation product of the CYP11B2 gene in human. [PRO:DNx, UniProtKB:P19099] | Homo sapiens (human) |
Cytochrome P450 11B1, mitochondrial | A cytochrome P450 11B that is a translation product of the CYP11B1 gene in human. [PRO:DNx, UniProtKB:P15538] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
fluconazole | fluconazole : 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 |
ketoconazole | 1-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 | |
letrozole | nitrile; triazoles | antineoplastic agent; EC 1.14.14.14 (aromatase) inhibitor | |
metyrapone | metyrapone : 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 ketone | antimetabolite; diagnostic agent; EC 1.14.15.4 (steroid 11beta-monooxygenase) inhibitor |
staurosporine | indolocarbazole alkaloid; organic heterooctacyclic compound | apoptosis inducer; bacterial metabolite; EC 2.7.11.13 (protein kinase C) inhibitor; geroprotector | |
fadrozole | Fadrozole: A selective aromatase inhibitor effective in the treatment of estrogen-dependent disease including breast cancer. | imidazopyridine | |
azalanstat | azalanstat: 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-benzylimidazole | 1-benzylimidazole: inhibits human thromboxane synthetase | ||
abiraterone | 3beta-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 | |
posaconazole | aromatic ether; conazole antifungal drug; N-arylpiperazine; organofluorine compound; oxolanes; triazole antifungal drug; triazoles | trypanocidal drug | |
1-(phenylmethyl)benzimidazole | benzimidazoles | ||
etomidate | etomidate : 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]benzimidazole | benzimidazoles | ||
4-fluoro-N-(3-pyridinyl)benzamide | carbonyl compound; organohalogen compound | ||
4-(1H-imidazol-1-ylmethyl)benzonitrile | benzenes; nitrile | ||
vorozole | vorozole: structure given in first source; vorozole/R 83842 is ((+)/dextro-isomer), RN 129731-10-8; R 83839 ((-)/levo-isomer) | benzotriazoles | |
osilodrostat | Osilodrostat: an orally active aldosterone-synthase inhibitor |