Differential Metabolic Stability of 4α,25- and 4β,25-Dihydroxyvitamin D₃ and Identification of Their Metabolites.

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 4β,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 4β,24R,25-trihydroxyvitamin D₃ (16a and 16b) as metabolites of

SUBMITTER: Mizumoto Y 

PROVIDER: S-EPMC10377336 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature