Vitamin d
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Vitamin d Presentation Transcript

  • 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. Structural differences of D2 and D33 In C-17 side chain, vitamin D2 has double bond andadditional methyl group.
  • 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. The active form5 The dihydroxylated vitamin D2 and D3 metabolitesare the active hormones.
  • 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. 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. 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. 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. 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 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. 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. 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. 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. 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. 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. Calcium homeostasis17
  • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.