Answer to Biochemistry Question N-03 : ( c ) Vitamin D
Vitamin D is synthesized from a derivative of cholesterol, the 7 dehydrocholesterol. By the action of hv light (290-315 nm) in the skin, it becomes cholecalciferol or Vitamin D3 (inactive).
Cholecalciferol is hydroxylated in the liver by 25 hydroxylase, and in the kidney by a 1 hydroxylase, becoming 1,25 dihydroxycholecalciferol or calcitriol, the active form of vitamin D3.
Vitamin D participates in the regulation of multiple processes, being the more obvious the regulation, together with Parathormone, of Ca++ homeostasis, regulating Ca++ in blood and the balance between Ca++ deposition and Ca++ mobilization from bone.
Hypocalcemia stimulates releasing of PTH, that through cAMP activates 1 hydroxylase in the conversion of VitD to calcitriol.
Calcitriol interacts with a vitamin D receptor (VDR) and initiates a cascade of molecular changes that stimulates the transcription of specific genes, including the synthesis of an intestinal Ca++ binding protein, essential for uptake of dietary Ca++. Together with PTH, Vitamin D facilitates Calcium reabsortion by the kidneys and mobilizes calcium from bone.
All these actions help bring back blood calcium levels within the normal range.
Intoxication with Vitamin D is usually a consequence of a prolonged ingestion of an overdose of supplements or as a consequence of accidents in the formulation of pills or in the misuse of some oils or containers.
The intoxication requires the prolonged ingestion of very excessive amounts of Vitamin D (around 100 times the Recommended Diary allowance) during a period of months, or an acute overdose of 10 000 times the RDA.
Vitamin D intoxication is characterized by hypercalcemia, hypercalciuria, gastrointestinal disorders, weak bones, deposits of calcium in soft tissue that can be revealed by imagen studies, renal calcium stones and kidney failure.
25 hydroxycolecalciferol is tipically elevated in serum.
General information about Vitamin D can be found in:
Linus Pauling Institute. Micronutrient Information Center. Vitamin D
Dusso, A.S. et al: Vitamin D
Am J Physiol Renal Physiol 289:F8-F28, 2005
Information about Vitamin D requirements and safety levels:
Amer J Clin Nut 69:5, 842-856, 1999
Muskiet, F.A.J. et al:
Amer J Clin Nutr 74: 6, 862-863, 2001
More about Vitamin D intoxication:
Klontz, K.C. and Acheson, D.W.: Dietary Supplement-induced vitamin D intoxication
NEJM, 357(3) 308-309, 2007
NEJM, 345 (1) 66-67, 2001