Target type: molecularfunction
Catalysis of the hydroxylation of C-25 of any form of vitamin D. [GOC:BHF, GOC:mah]
Vitamin D 25-hydroxylase activity is a crucial enzyme involved in the activation of vitamin D. It catalyzes the hydroxylation of vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol) at the C25 position, converting them into calcidiol, also known as 25-hydroxyvitamin D. This step is the first and rate-limiting step in the synthesis of the active form of vitamin D, calcitriol (1,25-dihydroxyvitamin D). The enzyme responsible for this activity is cytochrome P450 family 27 subfamily A member 1 (CYP27A1), which is primarily expressed in the liver.
The hydroxylation reaction involves the transfer of an oxygen atom from molecular oxygen to the C25 position of vitamin D, facilitated by the iron atom in the heme prosthetic group of CYP27A1. This process requires the reduction of CYP27A1 by NADPH and the transfer of electrons from NADPH-cytochrome P450 reductase.
The formation of calcidiol is essential because it serves as a circulating reservoir of vitamin D, allowing for sustained levels of active vitamin D to be maintained. Calcidiol is then further hydroxylated by 1α-hydroxylase to produce calcitriol, the biologically active form of vitamin D, in the kidneys. Calcitriol plays a vital role in calcium homeostasis, bone metabolism, and immune function.
In summary, vitamin D 25-hydroxylase activity is a critical step in the activation of vitamin D, converting inactive vitamin D forms into calcidiol, the circulating reservoir of vitamin D, which ultimately enables the production of the active form, calcitriol.'
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Protein | Definition | Taxonomy |
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1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial | A 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q07973] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
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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 | |
liarozole | liarozole: inhibits all-trans-retinoic acid 4-hydroxylase; effective against hormone-dependent and hormone-independent tumors; R 75251 is chlorohydrate of R 61405; a potent inhibitor of retinoic acid metabolism; USAN name - liarozole fumarate | benzimidazoles | |
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 | |
calcitriol | dihydroxy-vitamin D3: as a major in vitro metabolite of 1alpha,25-dihydroxyvitamin D3, produced in primary cultures of neonatal human keratinocytes | D3 vitamins; hydroxycalciol; triol | antineoplastic agent; antipsoriatic; bone density conservation agent; calcium channel agonist; calcium channel modulator; hormone; human metabolite; immunomodulator; metabolite; mouse metabolite; nutraceutical |