CYP24A1: structure, function, and physiological role

CYP24A1 is a mitochondrial inner-membrane cytochrome P450 enzyme that exhibits multifunctionality: it is able to hydroxylate both the C23 or the C24 side-chain carbons of 25(OH)D3 or 1,25(OH)2D3. The physiological relevance of these pathways has been confirmed in mice deficient for the Cyp24a1 gene. Considerable work has focused on structure–function analysis, and several homology models were described before the crystal structure of the rat CYP24A1 protein was reported. This chapter reviews the enzymatic pathways, the structure–function relationships, and the role of CYP24A1 in the catabolism of 1,25(OH)2D3. Mutations of CYP24A1 cause infantile hypercalcemia type 1 which can result in hypercalciuria, nephrolithiasis, and nephrocalcinosis in children and adults. In addition, biological roles of 24,25(OH)2D3, the main catalytic product, are presented.