The concept of vitamin d metabolism describes a sequence of biochemical steps that transform a vitamin D precursor into active signaling molecules. This pathway begins with a molecule that can be produced within the body or encountered through other means, and it relies on transport proteins to shuttle forms through circulation. Throughout the process, the metabolite pool is modulated by enzymes and regulatory signals, creating distinct forms with specific roles in the body's chemistry. In the liver, the first major step is 25-hydroxylation, carried out by hepatic enzymes such as CYP2R1, which convert the precursor into 25-hydroxyvitamin D (calcidiol). This circulating form serves as a reservoir and a substrate for further activation. The conversion is followed by transport in the bloodstream, aided by vitamin D binding protein, delivering the metabolite to sites where additional transformation can occur. The kidney performs the next crucial transformation: 1α-hydroxylation by the enzyme CYP27B1, producing 1,25-dihydroxyvitamin D (calcitriol), the hormonally active form. This step is tightly regulated by signaling pathways that monitor mineral status, including parathyroid hormone, phosphate levels, and fibroblast growth factor 23. In some tissues, local metabolism can also generate active or inactive forms, contributing to the broader network of vitamin d metabolism. Calcitriol exerts its effects by binding to the vitamin D receptor (VDR), a nuclear receptor that partners with other transcription factors to regulate gene expression. When the vitamin d metabolism pathway engages VDR, it influences the production of proteins involved in calcium transport and mineral balance, including intestinal transporters and binding partners. The system also includes a catabolic route via CYP24A1 that helps terminate signaling by inactivating vitamin D metabolites, maintaining overall balance within the pathway.
