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Vitamin d


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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 irradiationof provitamin D sterols. Vitamin D3 is produced by the action of sunlight on7-dehydrocholesterol in the skin.2
  3. 3. Structural differences of D2 and D33 In C-17 side chain, vitamin D2 has double bond andadditional methyl group.
  4. 4. Human activation41. Endogenous or dietary origin of vitamin D will behydroxylated 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 ofcarbon 1 to generate 1α,25-dihydroxyvitamin D[1α,25(OH)2D].
  5. 5. The active form5 The dihydroxylated vitamin D2 and D3 metabolitesare the active hormones.
  6. 6. Dietary sources6 The proportion of vitamin D obtained from the dietis very small compared with that synthesized in skinin 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 synthesis7 Vitamin D3 is synthesized in the skin from 7-dehydrocholesterol (provitamin D3). Provitamin D3 is converted photochemically toprevitamin D3, which converted to vitamin D3 by atemperature-dependent process (non enzymatic). The waveband of solar radiation responsible for theconversion of the provitamin to the previtamin isthat between 290 and 315 nm, known as the UV-Bband (less than 290 does not reach the earth).
  8. 8. Factors affecting vitamin D3 production81- AgeingThe skin becomes progressively thinner. The epidermalconcentration of 7-dehydrocholesterol decreases.Young adults produce 3 times more than elderly.2- Degree of skin pigmentationSkin pigmentation is a limiting factor for previtaminD3 synthesis because melanin competes with 7-dehydrocholesterol in absorbing UV-B radiation.3- Use of sunscreens
  9. 9. Intestinal absorption and transport9 Vitamin D is incorporated into chylomicrons, whenreleased, the chylomicrons convey the vitamin in themesenteric lymph to the systemic circulation. In the lymph, an appreciable amount of the vitaminD in the chylomicrons is transferred to the DBP. After lipolysis of the chylomicrons, the vitamin Dremaining on the chylomicron remnants, and also thevitamin D bound to protein, is initially taken up bythe liver.
  10. 10. Calcium and phosphate homeostasis101α,25-Dihydroxyvitamin D restores low plasmaconcentrations of Ca2+ and Pi to normal by action at thethree major targets; intestine, bone, kidney.a) stimulates the intestinal absorption of Ca2+ and Pi byindependent mechanisms,b) stimulates the transport of Ca2+ (accompanied by Pi)from the bone fluid compartment to the extracellularfluid compartment,c) facilitates the renal reabsorption of Ca2+. Thesethree mechanisms provide calcium for bonemineralization and prevent hypocalcaemic tetany.
  11. 11. 11 1α,25-Dihydroxyvitamin D3 regulates the synthesisof two classes of calcium-binding proteins(calbindins) found in mammalian intestine andkidney. An intestinal protein (calbindin-D9k) binds twocalcium ions per molecule, A renal protein (calbindin-D28k) binds five to sixcalcium ions per molecule.Calcium and phosphate homeostasis
  12. 12. Intestinal calcium absorption12 Calcium is present in foods and dietary supplements asrelatively insoluble salts. Calcium is absorbed only in ionized form, it must bereleased from the salts (mostly acidic medium). On reaching the alkaline environment of the smallintestine, some of the Ca2+ complex with minerals orother specific dietary constituents, thereby limitingcalcium bioavailability. Calcium absorption takes place by the translocation ofluminal Ca2+ through the enterocytes (transcellularroute) and between adjacent enterocytes via the tightjunctions (paracellular route).
  13. 13. The calbindin-based diffusional-activetransport model13This transcellular pathway is a complex processinvolving three steps:(1) entry by movement of Ca2+ from lumen throughthe brush-border membrane of the enterocyte,(2) intracellular diffusion,(3) extrusion from the cell across the basolateralmembrane. The major action of vitamin D inregulating this process is on the steps involved inCa2+ movement beyond brush-border entry.
  14. 14. Intestinal phosphate absorption14 Dietary phosphorus is a mixture of inorganic andorganic phosphorus. Phosphorus in meat and fish exists largely in theform 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 thejejunum by an energy-dependent transcellular route.
  15. 15. Vitamin D action on bone15 1α,25(OH)2D3 is required for normal development andmineralization of bone, and for bone remodelling. The effect of 1α,25(OH)2D3 on bone is indirect, beingattributable to the increased availability of calcium andphosphate for incorporation into bone that results fromthe increased intestinal absorption. Rickets can be cured in vitamin D-deficient rats byincreasing the calcium and phosphorus content of thediet or by maintaining normal circulating concentrationsof these minerals through infusion.
  16. 16. Vitamin D action on bone16 A major physiological function of 1α,25(OH)2D3 incalcium homeostasis is stimulation of bone resorption,which refers to localized bone dissolution by osteoclastswith resultant net calcium movement from bone toblood. The hormone acts by increasing the expression ofproteins essential to the resorptive process, proteins suchas carbonic anhydrase. The hormone also inhibits bone formation by decreasingalkaline phosphatase activity and collagen synthesis inosteoblasts and increasing the synthesis of osteocalcin,a potent inhibitor of mineralization.
  17. 17. Calcium homeostasis17
  18. 18. Phosphate homeostasis18 Unlike calcium, dietary phosphate usually exceeds thebody’s nutritional requirement, therefore a major componentof phosphate homeostasis is renal excretion. A diet that islow in phosphorus is likely to be low also in calcium, whichcomplicates the picture of phosphate homeostasis. A lowering of plasma phosphate will stimulate the kidney torelease 1α,25(OH)2D3, which elicits rapid and long-termresponses in the kidney, leading to increased renalreabsorption of phosphate. The 1α,25(OH)2D3 will also increase the intestinalabsorption of phosphate and calcium. The parathyroids willnot be stimulated to produce PTH.
  19. 19. Effects of vitamin D on insulin secretion19 1α,25-Dihydroxyvitamin D3 is considered to be amodulator of insulin secretion; Because…. vitamin D deficiency in rats is associatedwith marked impairment of insulin secretion and theinsulin-secreting β-cells of the pancreas contain thevitamin D-regulated protein calbindin-D28k.
  20. 20. Vitamin D-related diseases20Rickets The classic vitamin D deficiency disease in children. The disease is characterized by bow legs or knocksknees, curvature of the spine, and pelvic andthoracic bone deformities. These deformities result from the mechanical stressesof body weight and muscular activity applied to thesoft uncalcified bone.
  21. 21. Vitamin D-related diseases21Osteomalacia In adults, when the skeleton is fully developed,vitamin D is still necessary for the continuousremodelling of bone. During prolonged vitamin D deficiency, the newlyformed, uncalcified bone tissue gradually takes theplace of the older bone tissue and the weakenedbone structure is easily prone to fracture.
  22. 22. Toxicity22 Hypervitaminosis D results from the excessiveconsumption of vitamin D supplements, and not fromthe consumption of usual diets. Toxic concentrations of vitamin D have not resultedfrom unlimited exposure to sunshine. Vitamin D toxicity is due primarily to thehypercalcaemia caused by the increased intestinalabsorption of calcium, together with increasedresorption of bone.
  23. 23. Possible Interactions with Vitamin D23Vitamin D levels may be increased by the followingmedications: Estrogen: Hormone replacement therapy appears toincrease vitamin D levels in the blood; this may have abeneficial effect on calcium and bone metabolism. Inaddition, use of vitamin D supplements in conjunctionwith estrogen increases bone mass more than ERT alone. Isoniazid (INH): INH, a medication used to treattuberculosis, may raise blood levels of vitamin D. Thiazide: Diuretics in this class increase the activity ofvitamin D and can lead to inappropriately high calciumlevels in the blood.
  24. 24. Possible Interactions with Vitamin D24Vitamin D levels may be decreased, or its absorption may bereduced, by the following medications: Antacids: Taking antacids for long periods of time may alterthe levels, metabolism, and availability of vitamin D. Calcium channel blockers (as verapamil ): used to treat high(bp) and heart conditions, may decrease the production ofvitamin D by the body. Cholestyramine: cholesterol-lowering medication, known as abile acid sequestrant, interferes with the absorption ofvitamin D (as well as other fat-soluble vitamins). Phenobarbital (anticonvulsant): may accelerate the bodysuse of vitamin D.
  25. 25. Possible Interactions with Vitamin D25Weight 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 theabsorption of fat and the associated calories. Because of their effects on fat, orlistat and olestra mayalso prevent the absorption of fat-soluble vitamins suchas vitamin D. In addition, multivitamins with fat soluble vitamins willbe prescribed with orlistat to the regimen.
  26. 26. Dietary requirement26 The dietary requirement for vitamin D depends uponthe amount of vitamin synthesized by solar irradiationof the skin. Exposing hands, arms and face on a clear summer dayfor 10–15 min, two to three times a week, should yieldsufficient cutaneous production of vitamin D to meetdaily needs. To maintain satisfactory plasma 25(OH)D levels withoutany input from skin irradiation, an oral input in theregion of 10–15 μg of vitamin D per day would berequired.
  27. 27. References27 Caballero B (2005). Encyclopaedia of HumanNutrition. Second Esition. Elsevier Zempleni J, Rucker RB, McCormick DB, and SuttieJW (2007) Handbook of VITAMINS. Fourth Edition.Taylor & Francis Group. Bender D (2003). Nutritional Biochemistry of theVitamins. Second Edition. Cambridge UniversityPress.