Details

Autor(en) / Beteiligte

• Miller, Walter L.

Titel

Genetic disorders of Vitamin D biosynthesis and degradation

Ist Teil von

• The Journal of steroid biochemistry and molecular biology, 2017-01, Vol.165 (Pt A), p.101-108

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2017

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• [Display omitted] •Vitamin D is an inactive seco-steroid generated by opening the B-ring of 7-dehydrocholesterol in response to ultraviolet light.•Activation of vitamin D to 1,25(OH)2D requires 25-hydroxylation and 1α-hydroxylation; inactivation is mainly via 24-hydroxylation.•The three hydroxylations of vitamin D are catalyzed by cytochrome P450 enzymes: microsomal CYP2R1 and mitochondrial CYP27B1 and CYP24A1.•Genetic disorders of CYP2R1 and CYP27B1 cause hypocalcemia and rickets; disorders of CYP24A1 cause neonatal hypercalcemia.•Novel derivatives of vitamin D may be generated by cleavage of the cholesterol side chain via CYP11A1. Vitamin D, an inactive secosteroid pro-hormone, is produced by the action of ultraviolet light on 7-dehydrocholesterol in the skin. The active hormone, 1,25(OH)2D is produced by sequential 25-hydroxylation in the liver, principally by CYP2R1, and 1α-hydroxylation in the kidney by CYP27B1. Mutations in CYP27B1 cause 1α-hydroxylase deficiency, also known as vitamin D dependent rickets type I or hereditary pseudo-vitamin D deficient rickets; very rare mutations in CYP2R1 can cause 25-hydroxylase deficiency. Both deficiencies cause hypocalcemia, secondary hyperparathyroidism, severe rickets in infancy, and low serum concentrations of 1,25(OH)2D; both disorders respond to hormonal replacement therapy with calcitriol. The inactivation of vitamin D is principally initiated by its 23- and 24-hydroxylation by CYP24A1. Mutations in CYP24A1 can cause both severe neonatal hypercalcemia and a less severe adult hypercalcemic syndrome. Other pathways of vitamin D metabolism are under investigation, notably its 20-hydroxylation by the cholesterol side-chain cleavage enzyme, CYP11A1.