Abstract
Vitamin D is a prohormone synthesized in the skin from the precursor molecule 7-dehydrocholesterol by the action of sunlight. It is found in low amounts in food, with fortified dairy and fish oils being the most abundant source. Vitamin D undergoes an important 2-step bio-activation process required to produce the active metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D). The bio-activation process comprises the synthesis of 25-hydroxyvitamin D in the liver by 25-hydroxylation, followed by the conversion to 1,25(OH)2D by the 1α-hydroxylase in kidney under very tightly regulated physiological conditions. 1,25(OH)2D is responsible for maintaining adequate levels of calcium and phosphorus in the blood. Calcium is essential for muscles and nervous system functions, and through the actions of 1,25(OH)2D on intestine, kidney, and bone, the body prevents imbalances of both calcium and phosphate via an intricate system. In addition, 1,25(OH)2D plays an important role in many biological non-calcemic functions throughout the body. 1,25(OH)2D must bind to the vitamin D receptor to carry out its functions. The highly active and lipid soluble 1,25(OH)2D is inactivated by the 24-hydroxylase, which is the enzyme responsible for the major catabolic pathway that ultimately results in the water soluble calcitroic acid for excretion in the urine. Regulation of key players in vitamin D metabolism is reciprocal and very tight. The activating enzyme 1α-hydroxylase, and the catabolic enzyme 24-hydroxylase are reciprocally regulated by PTH, 1,25(OH)2D, and FGF23. Chronic kidney disease is associated with abnormalities of phosphorus homeostasis and altered vitamin D metabolism, and if left untreated, result in significant morbidity and mortality.
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Zierold, C., Martin, K.J., DeLuca, H.F. (2016). Vitamin D Metabolism in Normal and Chronic Kidney Disease States. In: Ureña Torres, P., Cozzolino, M., Vervloet, M. (eds) Vitamin D in Chronic Kidney Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-32507-1_1
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DOI: https://doi.org/10.1007/978-3-319-32507-1_1
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