CYP2R1 and vitamin D deficiency: However, there is evidence that the synthesis of 25(OH)D3 from cholecalciferol (vitamin D3) in the liver requires hydroxylation which depends on cytochrome P-450 25-hydroxylase (CYP2R1), a heme-containing enzyme, and thus, it is likely that iron deficiency might impair the synthesis of vitamin D3 leading to mild vitamin D deficiency [56].