Differential Metabolic Stability of 4α,25- and 4ß,25-Dihydroxyvitamin D3 and Identification of Their Metabolites.
Biomolecules
; 13(7)2023 06 24.
Article
en En
| MEDLINE
| ID: mdl-37509072
ABSTRACT
Vitamin D3 (1) is metabolized by various cytochrome P450 (CYP) enzymes, resulting in the formation of diverse metabolites. Among them, 4α,25-dihydroxyvitamin D3 (6a) and 4ß,25-dihydroxyvitamin D3 (6b) are both produced from 25-hydroxyvitamin D3 (2) by CYP3A4. However, 6b is detectable in serum, whereas 6a is not. We hypothesized that the reason for this is a difference in the susceptibility of 6a and 6b to CYP24A1-mediated metabolism. Here, we synthesized 6a and 6b, and confirmed that 6b has greater metabolic stability than 6a. We also identified 4α,24R,25- and 4ß,24R,25-trihydroxyvitamin D3 (16a and 16b) as metabolites of 6a and 6b, respectively, by HPLC comparison with synthesized authentic samples. Docking studies suggest that the ß-hydroxy group at C4 contributes to the greater metabolic stability of 6b by blocking a crucial hydrogen-bonding interaction between the C25 hydroxy group and Leu325 of CYP24A1.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Vitamina D
/
Colecalciferol
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
Biomolecules
Año:
2023
Tipo del documento:
Article
País de afiliación:
Japón