Genetics of vitamin D biosynthesis and its disorders

The principal hormone regulator of bone mineralization is vitamin D, which must be activated by a metabolic pathway consisting of a 25-hydroxylase and a 1α-hydroxylase to yield 1,25 (OH)2D. The hormonal regulation of vitamin D activation is at the level of the 1α-hydroxylase. We review the biology of vitamin D, the biochemistry of its activation and the molecular biology of the vitamin D-metabolizing enzymes. Recent advances have resulted in the cloning of the human vitamin D 1α-hydroxylase and the identification of mutations in its gene that cause Vitamin D Dependent Rickets type I.