Se ha denunciado esta presentación.

Vitamin d



Próximo SlideShare
Vitamin d presentation
Vitamin d presentation
Cargando en…3
4 de 27
4 de 27

Más Contenido Relacionado

Audiolibros relacionados

Gratis con una prueba de 14 días de Scribd

Ver todo

Vitamin d

  2. 2. Introduction  Vitamin D is represented by: 1. cholecalciferol (vitamin D3) 2. ergocalciferols (vitamin D2) (in plant, fungi, yeast)  they are structurally similar, derived from the UV irradiation of provitamin D sterols.  Vitamin D3 is produced by the action of sunlight on 7-dehydrocholesterol in the skin. 2
  3. 3. Structural differences of D2 and D3 3  In C-17 side chain, vitamin D2 has double bond and additional methyl group.
  4. 4. Human activation 4 1. Endogenous or dietary origin of vitamin D will be hydroxylated in the liver at carbon 25 to yield 25- hydroxyvitamin D [25(OH)D]. 2. This compound circulates in the blood and, 3. In the kidney, hydroxylation at the α-position of carbon 1 to generate 1α,25-dihydroxyvitamin D [1α,25(OH)2D].
  5. 5. The active form 5  The dihydroxylated vitamin D2 and D3 metabolites are the active hormones.
  6. 6. Dietary sources 6  The proportion of vitamin D obtained from the diet is very small compared with that synthesized in skin in response to sunlight.  Fish-liver oils,  Fatty fish as sardines,  Eggs and dairy products,  Cereals, vegetables and fruit contain no vitamin D,  Meat and poultry contribute insignificant amounts.
  7. 7. Cutaneous synthesis 7  Vitamin D3 is synthesized in the skin from 7- dehydrocholesterol (provitamin D3).  Provitamin D3 is converted photochemically to previtamin D3, which converted to vitamin D3 by a temperature-dependent process (non enzymatic).  The waveband of solar radiation responsible for the conversion of the provitamin to the previtamin is that between 290 and 315 nm, known as the UV-B band (less than 290 does not reach the earth).
  8. 8. Factors affecting vitamin D3 production 8 1- Ageing The skin becomes progressively thinner. The epidermal concentration of 7-dehydrocholesterol decreases. Young adults produce 3 times more than elderly. 2- Degree of skin pigmentation Skin pigmentation is a limiting factor for previtamin D3 synthesis because melanin competes with 7- dehydrocholesterol in absorbing UV-B radiation. 3- Use of sunscreens
  9. 9. Intestinal absorption and transport 9  Vitamin D is incorporated into chylomicrons, when released, the chylomicrons convey the vitamin in the mesenteric lymph to the systemic circulation.  In the lymph, an appreciable amount of the vitamin D in the chylomicrons is transferred to the DBP.  After lipolysis of the chylomicrons, the vitamin D remaining on the chylomicron remnants, and also the vitamin D bound to protein, is initially taken up by the liver.
  10. 10. Calcium and phosphate homeostasis 10 1α,25-Dihydroxyvitamin D restores low plasma concentrations of Ca2+ and Pi to normal by action at the three major targets; intestine, bone, kidney. a) stimulates the intestinal absorption of Ca2+ and Pi by independent mechanisms, b) stimulates the transport of Ca2+ (accompanied by Pi) from the bone fluid compartment to the extracellular fluid compartment, c) facilitates the renal reabsorption of Ca2+. These three mechanisms provide calcium for bone mineralization and prevent hypocalcaemic tetany.
  11. 11. 11  1α,25-Dihydroxyvitamin D3 regulates the synthesis of two classes of calcium-binding proteins (calbindins) found in mammalian intestine and kidney.  An intestinal protein (calbindin-D9k) binds two calcium ions per molecule,  A renal protein (calbindin-D28k) binds five to six calcium ions per molecule. Calcium and phosphate homeostasis
  12. 12. Intestinal calcium absorption 12  Calcium is present in foods and dietary supplements as relatively insoluble salts.  Calcium is absorbed only in ionized form, it must be released from the salts (mostly acidic medium).  On reaching the alkaline environment of the small intestine, some of the Ca2+ complex with minerals or other specific dietary constituents, thereby limiting calcium bioavailability.  Calcium absorption takes place by the translocation of luminal Ca2+ through the enterocytes (transcellular route) and between adjacent enterocytes via the tight junctions (paracellular route).
  13. 13. The calbindin-based diffusional-active transport model13 This transcellular pathway is a complex process involving three steps: (1) entry by movement of Ca2+ from lumen through the brush-border membrane of the enterocyte, (2) intracellular diffusion, (3) extrusion from the cell across the basolateral membrane. The major action of vitamin D in regulating this process is on the steps involved in Ca2+ movement beyond brush-border entry.
  14. 14. Intestinal phosphate absorption 14  Dietary phosphorus is a mixture of inorganic and organic phosphorus.  Phosphorus in meat and fish exists largely in the form of phosphoproteins and phospholipids (enzymatic hydrolysis).  80% of phosphorus in grains is found as phytic acid (bioavailability reduced).  Milk protein (casein) is highly phosphorylated.  Phosphate absorption takes place mainly in the jejunum by an energy-dependent transcellular route.
  15. 15. Vitamin D action on bone 15  1α,25(OH)2D3 is required for normal development and mineralization of bone, and for bone remodelling.  The effect of 1α,25(OH)2D3 on bone is indirect, being attributable to the increased availability of calcium and phosphate for incorporation into bone that results from the increased intestinal absorption.  Rickets can be cured in vitamin D-deficient rats by increasing the calcium and phosphorus content of the diet or by maintaining normal circulating concentrations of these minerals through infusion.
  16. 16. Vitamin D action on bone 16  A major physiological function of 1α,25(OH)2D3 in calcium homeostasis is stimulation of bone resorption, which refers to localized bone dissolution by osteoclasts with resultant net calcium movement from bone to blood.  The hormone acts by increasing the expression of proteins essential to the resorptive process, proteins such as carbonic anhydrase.  The hormone also inhibits bone formation by decreasing alkaline phosphatase activity and collagen synthesis in osteoblasts and increasing the synthesis of osteocalcin, a potent inhibitor of mineralization.
  17. 17. Calcium homeostasis 17
  18. 18. Phosphate homeostasis 18  Unlike calcium, dietary phosphate usually exceeds the body’s nutritional requirement, therefore a major component of phosphate homeostasis is renal excretion. A diet that is low in phosphorus is likely to be low also in calcium, which complicates the picture of phosphate homeostasis.  A lowering of plasma phosphate will stimulate the kidney to release 1α,25(OH)2D3, which elicits rapid and long-term responses in the kidney, leading to increased renal reabsorption of phosphate.  The 1α,25(OH)2D3 will also increase the intestinal absorption of phosphate and calcium. The parathyroids will not be stimulated to produce PTH.
  19. 19. Effects of vitamin D on insulin secretion 19  1α,25-Dihydroxyvitamin D3 is considered to be a modulator of insulin secretion;  Because…. vitamin D deficiency in rats is associated with marked impairment of insulin secretion and the insulin-secreting β-cells of the pancreas contain the vitamin D-regulated protein calbindin-D28k.
  20. 20. Vitamin D-related diseases 20 Rickets  The classic vitamin D deficiency disease in children.  The disease is characterized by bow legs or knocks knees, curvature of the spine, and pelvic and thoracic bone deformities.  These deformities result from the mechanical stresses of body weight and muscular activity applied to the soft uncalcified bone.
  21. 21. Vitamin D-related diseases 21 Osteomalacia  In adults, when the skeleton is fully developed, vitamin D is still necessary for the continuous remodelling of bone.  During prolonged vitamin D deficiency, the newly formed, uncalcified bone tissue gradually takes the place of the older bone tissue and the weakened bone structure is easily prone to fracture.
  22. 22. Toxicity 22  Hypervitaminosis D results from the excessive consumption of vitamin D supplements, and not from the consumption of usual diets.  Toxic concentrations of vitamin D have not resulted from unlimited exposure to sunshine.  Vitamin D toxicity is due primarily to the hypercalcaemia caused by the increased intestinal absorption of calcium, together with increased resorption of bone.
  23. 23. Possible Interactions with Vitamin D 23 Vitamin D levels may be increased by the following medications:  Estrogen: Hormone replacement therapy appears to increase vitamin D levels in the blood; this may have a beneficial effect on calcium and bone metabolism. In addition, use of vitamin D supplements in conjunction with estrogen increases bone mass more than ERT alone.  Isoniazid (INH): INH, a medication used to treat tuberculosis, may raise blood levels of vitamin D.  Thiazide: Diuretics in this class increase the activity of vitamin D and can lead to inappropriately high calcium levels in the blood.
  24. 24. Possible Interactions with Vitamin D 24 Vitamin D levels may be decreased, or its absorption may be reduced, by the following medications:  Antacids: Taking antacids for long periods of time may alter the levels, metabolism, and availability of vitamin D.  Calcium channel blockers (as verapamil ): used to treat high (bp) and heart conditions, may decrease the production of vitamin D by the body.  Cholestyramine: cholesterol-lowering medication, known as a bile acid sequestrant, interferes with the absorption of vitamin D (as well as other fat-soluble vitamins).  Phenobarbital (anticonvulsant): may accelerate the body's use of vitamin D.
  25. 25. Possible Interactions with Vitamin D 25 Weight loss products:  Orlistat, a medication used for weight loss, and  Olestra, a substance added to certain food products,  The both intended to bind to fat and prevent the absorption of fat and the associated calories.  Because of their effects on fat, orlistat and olestra may also prevent the absorption of fat-soluble vitamins such as vitamin D.  In addition, multivitamins with fat soluble vitamins will be prescribed with orlistat to the regimen.
  26. 26. Dietary requirement 26  The dietary requirement for vitamin D depends upon the amount of vitamin synthesized by solar irradiation of the skin.  Exposing hands, arms and face on a clear summer day for 10–15 min, two to three times a week, should yield sufficient cutaneous production of vitamin D to meet daily needs.  To maintain satisfactory plasma 25(OH)D levels without any input from skin irradiation, an oral input in the region of 10–15 μg of vitamin D per day would be required.
  27. 27. References 27  000995.htm#ixzz2R6E5HYwi.  Caballero B (2005). Encyclopaedia of Human Nutrition. Second Esition. Elsevier  Zempleni J, Rucker RB, McCormick DB, and Suttie JW (2007) Handbook of VITAMINS. Fourth Edition. Taylor & Francis Group.  Bender D (2003). Nutritional Biochemistry of the Vitamins. Second Edition. Cambridge University Press.