25-Hydroxyvitamin D3 1-alpha-hydroxylase

25-Hydroxyvitamin D3 1-alpha-hydroxylase is an enzyme responsible for the hydroxylation of 25-hydroxyvitamin D3 (calcidiol) into 1,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D. This enzyme plays a crucial role in the vitamin D metabolism and is essential for calcium homeostasis and bone metabolism. The gene that encodes this enzyme is located on chromosome 12q13.3 and is known as CYP27B1.

Function[edit | edit source]

25-Hydroxyvitamin D3 1-alpha-hydroxylase is primarily found in the kidney, but it is also present in other tissues including the skin, placenta, and immune system cells. The enzyme's activity is tightly regulated by several factors including serum levels of phosphorus, calcium, and parathyroid hormone (PTH). When calcium levels are low, PTH is secreted, which in turn increases the activity of 25-Hydroxyvitamin D3 1-alpha-hydroxylase, leading to increased production of calcitriol. Calcitriol then acts to increase calcium absorption from the gut, reabsorption in the kidneys, and release from the bones, thereby raising serum calcium levels.

Clinical Significance[edit | edit source]

Mutations in the CYP27B1 gene can lead to a rare, inherited form of rickets known as vitamin D-dependent rickets type 1 (VDDR-1), characterized by low levels of calcium and phosphate in the blood due to reduced levels of calcitriol. Symptoms of VDDR-1 include bone pain, muscle weakness, and skeletal deformities. Treatment typically involves supplementation with calcitriol and calcium.

In addition, the regulation of 25-Hydroxyvitamin D3 1-alpha-hydroxylase is of interest in the context of autoimmune diseases, such as multiple sclerosis (MS) and rheumatoid arthritis (RA), as well as in the prevention and treatment of certain cancers. There is evidence to suggest that vitamin D, through its active form calcitriol, may have immunomodulatory and anti-proliferative effects.

Regulation[edit | edit source]

The activity of 25-Hydroxyvitamin D3 1-alpha-hydroxylase is influenced by several factors: - **Calcium and Phosphorus Levels:** Low levels stimulate, while high levels inhibit its activity. - **Parathyroid Hormone (PTH):** Increases the enzyme's activity. - **Fibroblast Growth Factor 23 (FGF23):** Inhibits the enzyme's activity. - **Phosphate:** High levels of phosphate can inhibit the enzyme's activity.

Genetic Regulation[edit | edit source]

The CYP27B1 gene is regulated by various factors including PTH, calcium, and phosphorus levels. Genetic mutations in CYP27B1 can lead to impaired function of the enzyme, resulting in disorders of vitamin D metabolism such as VDDR-1.