Vitamin D or the sunshine vitamin is a prohormone that can be either obtained from the diet or synthesized from a cholesterol precursor that requires reactions in the skin, liver and kidney. Its overall function is to maintain adequate plasma Ca+2 levels and is also called the hypercalcemic hormone.
Synthesis of Vitamin D involves the reaction of 7-dehydrocholesterol or Provit. D3 in the skin with the UV rays of the sun to form Previt. D3. Previt. D3 is then isomerized to cholecalciferol (Vit. D3) in the dermal and epidermal layers of the skin. Vit D3 is then brought to the blood to undergo two hydroxylation reactions on the two organs namely the liver and kidneys. The first hydroxylation reaction, in the liver, involves the opening of the Vit D3 structure and the hydroxylation in the presence of cytochrome P450, O2 and NADPH as cofactors, catalyzed by 25-hydroxylase, forming 25-hydroxycholecalciferol or Calcidiol, the predominant form of Vit D bound to a binding globulin, present in the plasma and the major storage form of Vit D. The second hydroxylation reaction, calcidiol is then brought to the kidneys via the blood and undergo further hydroxylation via 25-hydroxycholecalciferol 1-hydroxylase (again in the presence of the previous cofactors in the 1st hydroxylation reaction) to form 1,25-dihydroxycholecalciferol or Calcitriol, the most biologically active form of Vit. D and is the most potent Vit. D metabolite.
Synthesis of Vitamin D involves the reaction of 7-dehydrocholesterol or Provit. D3 in the skin with the UV rays of the sun to form Previt. D3. Previt. D3 is then isomerized to cholecalciferol (Vit. D3) in the dermal and epidermal layers of the skin. Vit D3 is then brought to the blood to undergo two hydroxylation reactions on the two organs namely the liver and kidneys. The first hydroxylation reaction, in the liver, involves the opening of the Vit D3 structure and the hydroxylation in the presence of cytochrome P450, O2 and NADPH as cofactors, catalyzed by 25-hydroxylase, forming 25-hydroxycholecalciferol or Calcidiol, the predominant form of Vit D bound to a binding globulin, present in the plasma and the major storage form of Vit D. The second hydroxylation reaction, calcidiol is then brought to the kidneys via the blood and undergo further hydroxylation via 25-hydroxycholecalciferol 1-hydroxylase (again in the presence of the previous cofactors in the 1st hydroxylation reaction) to form 1,25-dihydroxycholecalciferol or Calcitriol, the most biologically active form of Vit. D and is the most potent Vit. D metabolite.
Calcidiol (25-hydroxycholecalciferol)
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Calcitriol (1,25-dihydroxycholecalciferol)
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There are different factors in the body that alters the production of Vitamin D. Low plasma PO43- increases the activity of 25-OH-cholecalciferol 1-hydroxylase which will increase the production of Calcitriol. Low plasma Ca+2 trigger the release of PTH which can also stimulate the production of Calcitriol. Since this is fat soluble, Vit. D can penetrate the phospholipid bilayered membrane of the target cell via passive diffusion. In the cytoplasm, Vit. D will then bind to its receptor forming the Vit. D3-receptor complex that will enter the nucleus, interacts with the DNA and will selectively stimulate gene expression or specifically repress gene expression (Madarcos, 2013).
Vitamin D as it is generally used to maintain adequate plasma Ca+2 levels has different effects on the functions of the intestine, bone and the kidneys as to the regulation of calcium. In the intestines, Vit. D stimulates dietary absorption of calcium by inducing the synthesis of calcium transport protein (TRPV5) and calcium-binding protein (calbindin) which are both required for calcium transport. In the bones, it stimulates the mobilization of calcium (and phosphate) from bone by stimulation osteoblast formation and activity. In the kidneys, it stimulate Ca+2 excretion by stimulating calcium reabsorption in the distal tubules (Madarcos, 2013).
According to Madarcos (2013) in the second hydroxylation reaction, kidneys can also produce inactive vitamin D via the enzyme 24-hydroxylase. This reaction will yield 24,25-(OH)2-D the inactive metabolite. Prolonged intake of steroids promotes the synthesis of inactive vitamin D, therefore dimeniralization of bones will happen due to lack of absorption of calcium in the body. This phenomenon can be one of the causes of vitamin D deficiency.
Vitamin D deficiency can happen due to certain factors like lack of sunlight exposure, renal failure and many different factors involving the pathway of conversion to calcitriol. According to Murray et. al. (2009) The most common diseases related to vitamin D deficiency is rickets where the bones of the children are under mineralized as a result of poor absorption of calcium. Another disease is called osteomalacia, which results from the demineralization of bone, and occurs especially in women who have little exposure to sunlight, especially after several pregnancies.
Some infants are sensitive to vitamin D toxicity resulting to an elevated plasma concentration of calcium. Hypercalcemia can lead to contraction of blood vessels, high blood pressure, and calcinosis or the calcification of soft tissues. Although excess vitamin D is toxic, excessive exposure to sunlight will not lead to over production of vitamin D because there is a limited capacity to form the precursor, 7-dehydrocholesterol, and prolonged exposure of previtamin D to sunlight leads to formation of inactive compounds (Murray et al. 2009).
Vitamin D as it is generally used to maintain adequate plasma Ca+2 levels has different effects on the functions of the intestine, bone and the kidneys as to the regulation of calcium. In the intestines, Vit. D stimulates dietary absorption of calcium by inducing the synthesis of calcium transport protein (TRPV5) and calcium-binding protein (calbindin) which are both required for calcium transport. In the bones, it stimulates the mobilization of calcium (and phosphate) from bone by stimulation osteoblast formation and activity. In the kidneys, it stimulate Ca+2 excretion by stimulating calcium reabsorption in the distal tubules (Madarcos, 2013).
According to Madarcos (2013) in the second hydroxylation reaction, kidneys can also produce inactive vitamin D via the enzyme 24-hydroxylase. This reaction will yield 24,25-(OH)2-D the inactive metabolite. Prolonged intake of steroids promotes the synthesis of inactive vitamin D, therefore dimeniralization of bones will happen due to lack of absorption of calcium in the body. This phenomenon can be one of the causes of vitamin D deficiency.
Vitamin D deficiency can happen due to certain factors like lack of sunlight exposure, renal failure and many different factors involving the pathway of conversion to calcitriol. According to Murray et. al. (2009) The most common diseases related to vitamin D deficiency is rickets where the bones of the children are under mineralized as a result of poor absorption of calcium. Another disease is called osteomalacia, which results from the demineralization of bone, and occurs especially in women who have little exposure to sunlight, especially after several pregnancies.
Some infants are sensitive to vitamin D toxicity resulting to an elevated plasma concentration of calcium. Hypercalcemia can lead to contraction of blood vessels, high blood pressure, and calcinosis or the calcification of soft tissues. Although excess vitamin D is toxic, excessive exposure to sunlight will not lead to over production of vitamin D because there is a limited capacity to form the precursor, 7-dehydrocholesterol, and prolonged exposure of previtamin D to sunlight leads to formation of inactive compounds (Murray et al. 2009).