Hepatic Transport of 25-Hydroxyvitamin D3 Conjugates: A Mechanism of 25-Hydroxyvitamin D3 Delivery to the Intestinal Tract

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Chunying GaoQingcheng Mao

Abstract

Vitamin D3 is an important prohormone critical for maintaining calcium and phosphate homeostasis in the body and regulating drug-metabolizing enzymes and transporters. 25-Hydroxyvitamin D3 (25OHD3), the most abundant circulating metabolite of vitamin D3, is further transformed to the biologically active metabolite 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) by CYP27B1 in the kidney and extrarenal tissues, and to nonactive metabolites by other cytochrome P450 enzymes. In addition, 25OHD3 undergoes sulfation and glucuronidation in the liver, forming two major conjugative metabolites, 25OHD3-3-O-sulfate (25OHD3-S) and 25OHD3-3-O-glucuronide (25OHD3-G), both of which were detected in human blood and bile. Considering that the conjugates excreted into the bile may be circulated to and reabsorbed from the intestinal lumen, deconjugated to 25OHD3, and then converted to 1α,25-(OH)2D3, exerting local intestinal cellular effects, it is crucial to characterize enterohepatic transport mechanisms of 25OHD3-S and 25OHD3-G, and thereby understand and predict mechanisms of interindividual variability in mineral homeostasis. In the present study, with plasma membrane vesicle and cell-based transport studies, we showed that 25OHD3-G is a substrate...Continue Reading

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Citations

Nov 30, 2018·Drug Metabolism Letters·Lyrialle W HanQingcheng Mao
Apr 11, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Qingcheng MaoJoanne Wang
Jul 13, 2020·Experimental Dermatology·Michal A Zmijewski, Carsten Carlberg
Jul 7, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Carmen J ReynoldsJesse P Goff
Mar 19, 2021·British Journal of Clinical Pharmacology·Brian D ChapronJ Steven Leeder
Jun 3, 2021·International Journal of Molecular Sciences·Robert Gironés PetitElena Sánchez-López
Sep 13, 2021·Molecular Nutrition & Food Research·Tiffany AntoineEmmanuelle Reboul

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