25hydroxylase

25-hydroxylase refers to enzymes that catalyze the hydroxylation of vitamin D at the 25-position, producing 25-hydroxyvitamin D [25(OH)D], the primary circulating form of vitamin D and a standard marker of vitamin D status. In humans, the main enzyme performing this reaction in the liver is cytochrome P450 family 2 subfamily member 1, known as CYP2R1. Additional 25-hydroxylation activity has been reported for other cytochrome P450 enzymes, notably CYP27A1, and under certain conditions for others such as CYP3A4, though their contributions are typically smaller.

Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) serve as substrates for 25-hydroxylation. The resulting 25(OH)D is transported in the circulation bound to vitamin D binding protein and generally has a longer half-life than the parent vitamins. 25(OH)D serves as the major circulating reservoir and is used clinically to assess vitamin D status.

After 25-hydroxylation, 25(OH)D can undergo further activation in the kidney by 1α-hydroxylase (CYP27B1), producing 1,25-dihydroxyvitamin D [1,25(OH)2D], the hormonally active form. Extrahepatic 1α-hydroxylation can also occur in other tissues. Genetic variation in CYP2R1 can reduce 25-hydroxylase activity, leading to lower serum 25(OH)D and, in some cases, vitamin D–related deficiencies or rickets. Overall, 25-hydroxylase activity is a crucial initial step in the metabolic activation and regulation of vitamin D.