1hydroxylas

1-hydroxylase, also known as 1α-hydroxylase, is an enzyme that catalyzes the hydroxylation of 25-hydroxyvitamin D [25(OH)D] at the 1-alpha position to form 1,25-dihydroxyvitamin D [1,25(OH)2D], the hormonally active form of vitamin D. In humans, the enzyme is encoded by the CYP27B1 gene and is a key regulatory step in vitamin D metabolism. It is primarily expressed in the proximal tubules of the kidneys, where its activity controls the amount of active vitamin D produced. Extra-renal expression has been reported in immune cells such as macrophages and in certain epithelial tissues, where local calcitriol production may occur.

Regulation of 1α-hydroxylase activity is complex. It is stimulated by parathyroid hormone (PTH), low circulating calcium or phosphate, and low levels of 1,25(OH)2D. It is inhibited by negative feedback from calcitriol itself and by high phosphate or high levels of 1,25(OH)2D, as well as by fibroblast growth factor 23 (FGF23). This regulatory network helps maintain calcium and phosphate homeostasis and bone health.

Physiological role of the enzyme’s product, calcitriol, includes increasing intestinal absorption of calcium and phosphate, promoting bone mineralization, and modulating immune function. Activation of vitamin D via 1α-hydroxylase is therefore central to mineral metabolism and overall calcium balance.

Clinical significance can arise from CYP27B1 disturbances. Loss-of-function mutations cause vitamin D-dependent rickets type 1 (VDDR-I), a disorder of impaired calcitriol production that leads to hypocalcemia and bone deformities, often treated with active vitamin D analogs. Reduced renal 1α-hydroxylase activity is common in chronic kidney disease, contributing to disturbed mineral metabolism. Conversely, excess calcitriol production can occur in granulomatous diseases, causing hypercalcemia.