1,25-dihydroxyvitamin D

Definition

A cytochrome P450 monooxygenase with a key role in vitamin D catabolism and calcium homeostasis. Via C24- and C23-oxidation pathways, catalyzes the inactivation of both the vitamin D precursor calcidiol (25-hydroxyvitamin D(3)) and the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)). With initial hydroxylation at C-24 (via C24-oxidation pathway), performs a sequential 6-step oxidation of calcitriol leading to the formation of the biliary metabolite calcitroic acid. With initial hydroxylation at C-23 (via C23-oxidation pathway), catalyzes sequential oxidation of calcidiol leading to the formation of 25(OH)D3-26,23-lactone as end product. Preferentially hydroxylates at C-25 other vitamin D active metabolites, such as CYP11A1-derived secosteroids 20S-hydroxycholecalciferol and 20S,23-dihydroxycholecalciferol. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via FDXR/adrenodoxin reductase and FDX1/adrenodoxin.

References:

[1]. Toshiyuki Sakaki, et al. Metabolism of vitamin D3 by cytochromes P450. Front Biosci. 2005 Jan 1;10:119-34. [Content Brief]

[2]. Jeffrey D Roizen, et al. CYP3A4 mutation causes vitamin D-dependent rickets type 3. J Clin Invest. 2018 May 1;128(5):1913-1918. [Content Brief]

[3]. M J Beckman, et al. Human 25-hydroxyvitamin D3-24-hydroxylase, a multicatalytic enzyme. Biochemistry. 1996 Jun 25;35(25):8465-72. [Content Brief]

[4]. T Sakaki, et al. Dual metabolic pathway of 25-hydroxyvitamin D3 catalyzed by human CYP24. Eur J Biochem. 2000 Oct;267(20):6158-65. [Content Brief]

[5]. Elaine W Tieu, et al. Kinetic analysis of human CYP24A1 metabolism of vitamin D via the C24-oxidation pathway. FEBS J. 2014 Jul;281(14):3280-96. [Content Brief]

[6]. Elaine W Tieu, et al. Metabolism of 20-hydroxyvitamin D3 and 20,23-dihydroxyvitamin D3 by rat and human CYP24A1. J Steroid Biochem Mol Biol. 2015 May;149:153-65. [Content Brief]

[7]. Hiromi Hamamoto, et al. Structure-function analysis of vitamin D 24-hydroxylase (CYP24A1) by site-directed mutagenesis: amino acid residues responsible for species-based difference of CYP24A1 between humans and rats. Mol Pharmacol. 2006 Jul;70(1):120-8. [Content Brief]

生物医学辞典

生物医学辞典は、生物学の学術用語と専門データの包括的で専門的なデータベースです。すべての説明は、権威ある書籍や高いＩＦの文献に基づいており、知りたい生物医学用語の正確な説明を得ることができます。

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z #

お名前
メール *

	Sorry, but the email address you supplied was invalid.