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Introduction to Human Cytochrome P450 Superfamily
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
For example, CYP2R1, 3A4, 2J3, 24A1, 27A1, and 27B1 all metabolize vitamin D3 (Jones et al. 2014; Omdahl et al. 2003; Prosser and Jones 2004; Sakaki et al. 2005). During activation, vitamin D first undergoes hydroxylation by hepatic 25-hydroxylase (CYP2R1), resulting in 25(OH)D3. A second hydroxylation by renal 1α-hydroxylase (CYP27B1) forms the active form 1,25(OH)2D3, which exerts its biological effects by binding to the vitamin D receptor (VDR). This active form of vitamin D is inactivated by 24-hydroxylase (CYP24A1), an enzyme that is responsible for the five-step 24-oxidation pathway from 1,25(OH)2D3 to calcitroic acid (Sakaki et al. 2005). Vitamin D plays a central role in calcium homeostasis and bone metabolism (St-Arnaud 2008). Multiple CYPs play an important role in maintenance of cholesterol homeostasis. CYP51 is involved in cholesterol biosynthesis, whereas CYP 7A1, 27A1, 46A1, 7B1, 39A1, and 8B1 are the key enzymes in cholesterol catabolism to bile acids, the major route of cholesterol elimination (Pikuleva 2006). Conversion of cholesterol to steroids is initiated by CYP11A1, and CYP3A4 contributes to bile acid biosynthesis as well (Pikuleva 2006). Six CYPs including the CYP11 family and three type II CYPs including CYP17A1, 19A1, and 21A2 play indispensable roles in the biosynthesis of steroids. The key CYP enzymes in the bile acid biosynthetic pathways are CYP7A1, 8B1, 27A1, and 7B1. Biosynthesis and metabolism of cholesterol, bile acids, and oxysterols involve CYP3A4, 7A1, 7B1, 8B1, 27A1, 39A1, 46A1, and 51A1.
Associations of genetic polymorphisms of the vitamin D pathway with blood pressure in a Han Chinese population
Published in Clinical and Experimental Hypertension, 2019
Xiaoman Ye, Jian Jia, Ning Zhang, Haixia Ding, Yiyang Zhan
Vitamin D in human serum is derived mainly from food intake and self-synthesis in vivo. With exposure to sunlight, UVB radiation transforms 7-dehydrocholesterol in the skin into previtamin D3, which is unstable and converts rapidly to vitamin D3 (3). It is converted to 25-hydroxyvitamin D3 [25(OH)D3] in the liver through the 25-hydroxylases cytochrome P450 family 2 subfamily R member 1(CYP2R1) and cytochrome P450 family 27 subfamily A member 1(CYP27A1) (14). In the kidney, 25(OH)D3 can be converted through 1-α-hydroxylase (CYP27B1) to its active form 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 25(OH)D3 and 1,25-dihydroxyvitamin D3 are catabolized into biologically inactive, water-soluble calcitroic acid by the enzyme 25-hydroxyvitamin D-24-hydroxylase (CYP24A1) (13). Some studies have shown that genetic mutation of the key enzyme may influence 25(OH)D3 status in some African and European countries (15–18), but little research has been conducted in Han Chinese populations.
Vitamin D: sources, physiological role, biokinetics, deficiency, therapeutic use, toxicity, and overview of analytical methods for detection of vitamin D and its metabolites
Published in Critical Reviews in Clinical Laboratory Sciences, 2022
Jiří Janoušek, Veronika Pilařová, Kateřina Macáková, Anderson Nomura, Jéssica Veiga-Matos, Diana Dias da Silva, Fernando Remião, Luciano Saso, Kateřina Malá-Ládová, Josef Malý, Lucie Nováková, Přemysl Mladěnka
The second step in the activation of vitamin D is the conversion of 25(OH)D2/3 to its biologically active form calcitriol [1,25(OH)2D2/3] by the CYP27B1. This conversion takes place either in the kidneys or in a number of extrarenal tissues. Inactivation of calcitriol is ensured by the 24-hydroxylation, promoted by CYP24A1 (Figure 4). This enzyme is expressed in most cells and is induced by elevation in calcitriol plasma concentrations, representing negative feedback protection against hypercalcemia. The formed 1,24,25(OH)3D has low biological activity and is further metabolized in the liver and kidneys into calcitroic acid, the major inactive vitamin D metabolite, which is excreted into the bile [125].
Vitamin D attenuates biofilm-associated infections via immunomodulation and cathelicidin expression: a narrative review
Published in Expert Review of Anti-infective Therapy, 2023
Ruby Benson, Mazhuvancherry Kesavan Unnikrishnan, Shilia Jacob Kurian, Saleena Ummer Velladath, Gabriel Sunil Rodrigues, Raghu Chandrashekar Hariharapura, Anju Muraleedharan, Dinesh Bangalore Venkateshiah, Barnini Banerjee, Chiranjay Mukhopadhyay, Aieshel Serafin Johnson, Murali Munisamy, Mahadev Rao, Benson Mathai Kochikuzhyil, Sonal Sekhar Miraj
To function, 1,25-dihydroxyvitamin D binds to and activates the vitamin D receptor. This active complex forms a heterodimer with the retinoid X receptor (RXR). To exert genomic effects, the heterodimer is recruited to vitamin D response elements (VDRE) of target genes [30]. When the effects of vitamin D are no longer needed, the active VDR-RXR heterodimer binds to the CYP24A1 gene’s VDRE and codes for the 24-hydroxylase enzyme. This enzyme regulates vitamin D levels by converting 1,25-dihydroxyvitamin D to calcitroic acid (1-hydroxy-23-carboxy-24,25,26,27-tetranorvitamin D3), which is excreted in bile [31]. Since the identification of VDR in different cells, health claims for vitamin D have multiplied in Western nations [32].