Vitamin D3 24-hydroxylase

Vitamin D3 24-hydroxylase is an enzyme that plays a crucial role in the metabolism of vitamin D. It is encoded by the CYP24A1 gene in humans. This enzyme is involved in the inactivation and degradation of 1,25-dihydroxyvitamin D3 (the active form of vitamin D), by hydroxylating it to form calcitroic acid. Vitamin D3 24-hydroxylase is found in various tissues, including the kidney and intestine, which are key sites for vitamin D metabolism.

Function

Vitamin D3 24-hydroxylase catalyzes the hydroxylation of the 24 position of vitamin D metabolites, which leads to the inactivation of these compounds. The enzyme's activity is crucial for maintaining the proper balance of vitamin D in the body, preventing both deficiency and toxicity. It acts on both forms of vitamin D: D2 (ergocalciferol) and D3 (cholecalciferol), but its primary substrate is 1,25-dihydroxyvitamin D3, the hormonally active form of vitamin D.

Genetics

The CYP24A1 gene, located on chromosome 20q13.2, encodes the Vitamin D3 24-hydroxylase enzyme. Mutations in this gene can lead to abnormalities in vitamin D metabolism, resulting in conditions such as Hypercalcemia and Hypercalciuria, due to the reduced ability to degrade active vitamin D.

Clinical Significance

Abnormalities in the function or expression of vitamin D3 24-hydroxylase can have significant clinical implications. Overactivity of this enzyme can lead to vitamin D deficiency, with symptoms ranging from bone disorders like osteomalacia in adults and rickets in children, to muscle weakness and immune system issues. Conversely, underactivity can result in vitamin D toxicity, characterized by hypercalcemia and associated health problems.

Regulation

The activity of vitamin D3 24-hydroxylase is regulated by several factors, including levels of parathyroid hormone, calcium, and phosphate in the blood, as well as by the concentration of 1,25-dihydroxyvitamin D3 itself. This regulation ensures that vitamin D levels remain within a narrow, healthy range.

Research Directions

Research into vitamin D3 24-hydroxylase is ongoing, with studies focusing on understanding its role in diseases related to vitamin D imbalance, such as certain cancers, autoimmune diseases, and cardiovascular diseases. There is also interest in developing drugs that can modulate the activity of this enzyme to treat conditions related to vitamin D deficiency or toxicity.