TY - GEN
T1 - 25-Hydroxyvitamin D3 24-Hydroxylase. A Key Regulator of 1,25(OH)2D3 Catabolism and Calcium Homeostasis.
AU - Veldurthy, Vaishali
AU - Wei, Ran
AU - Campbell, Megan
AU - Lupicki, Kamil
AU - Dhawan, Puneet
AU - Christakos, Sylvia
N1 - Funding Information:
S.C. receives funding from the National Institutes of Health (AI-100379, AG044552).
PY - 2016
Y1 - 2016
N2 - One of the most pronounced effects of the hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is increased synthesis of 25-hydroxyvitamin D3 24-hydroxylase (CYP24A1), the enzyme responsible for the catabolism of 1,25(OH)2D3. Thus, 1,25(OH)2D3 regulates its own metabolism, protecting against hypercalcemia and limiting the levels of 1,25(OH)2D3 in cells. This chapter summarizes the catalytic properties of CYP24A1, the recent data related to the crystal structure of CYP24A1, the findings obtained from the generation of mice deficient for the Cyp24a1 gene as well as recent data identifying a causal role of a genetic defect in CYP24A1 in certain patients with idiopathic infantile hypercalcemia. This chapter also reviews the regulation of renal and placental CYP24A1 as well as the genomic mechanisms, including coactivators, repressors, and epigenetic modification, involved in modulating 1,25(OH)2D3 regulation of CYP24A1. We conclude with future research directions related to this key regulator of 1,25(OH)2D3 catabolism and calcium homeostasis.
AB - One of the most pronounced effects of the hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is increased synthesis of 25-hydroxyvitamin D3 24-hydroxylase (CYP24A1), the enzyme responsible for the catabolism of 1,25(OH)2D3. Thus, 1,25(OH)2D3 regulates its own metabolism, protecting against hypercalcemia and limiting the levels of 1,25(OH)2D3 in cells. This chapter summarizes the catalytic properties of CYP24A1, the recent data related to the crystal structure of CYP24A1, the findings obtained from the generation of mice deficient for the Cyp24a1 gene as well as recent data identifying a causal role of a genetic defect in CYP24A1 in certain patients with idiopathic infantile hypercalcemia. This chapter also reviews the regulation of renal and placental CYP24A1 as well as the genomic mechanisms, including coactivators, repressors, and epigenetic modification, involved in modulating 1,25(OH)2D3 regulation of CYP24A1. We conclude with future research directions related to this key regulator of 1,25(OH)2D3 catabolism and calcium homeostasis.
KW - 25-Hydroxyvitamin D 24-hydroxylase
KW - Fibroblast growth factor 23
KW - Parathyroid hormone
KW - Transcription
KW - Vitamin D receptor
UR - http://www.scopus.com/inward/record.url?scp=84952361021&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84952361021&partnerID=8YFLogxK
U2 - 10.1016/bs.vh.2015.10.005
DO - 10.1016/bs.vh.2015.10.005
M3 - Conference contribution
C2 - 26827951
AN - SCOPUS:84952361021
SN - 9780128048245
T3 - Vitamins and Hormones
SP - 137
EP - 150
BT - Vitamin D Hormone, 2016
A2 - Litwack, Gerald
PB - Academic Press Inc.
ER -