6.2025 FAT-SOLUBLE VITAMINS as hormones.pptx

Fat soluble vitamins as hormones

1. Fat-soluble vitamins (A, D, E, K). Vitaminotherapy Dr. Mahira Amirova Associate Professor Biochemistry Department Azerbaijan Medical University Year 2025 In The Name of Allah, The Most Merciful, The Most Compassionate Yağda həll olan vitaminlər. Vitaminəbənzər maddələr. Antivitaminlər. Vitaminoterapiya. Mikroelementlər.

2.   OBJECTIVES General overview Vitamins general characteristics Fat soluble vitamins structure Fat soluble vitamins action mechanism Fat soluble vitamins functions Fat soluble vitamins deficiency symptoms Fat soluble vitamins dietary sources

3.   INTRODUCTION : vitamins concept The term "vitamin" comes from the Latin word “vita” - "life“ and amines, as firs vitamin has discovered (B 1 ) comprises amine group. Vitamins are not the structural compounds of the body. Vitamins are not used as energetic fuel for the cells. Vitamins are the essential organic dietary compounds needed in very small amounts for growth and maintaining health, ergo everybody should take vitamins to stay healthy. Vitamins are chemicals found in small amounts in many different foods, ergo to stay healthy we would better mix the dietary products .

4. FAT SOLUBLE VITAMINS These are vitamins dissolved in lipids (fat). As fat is easily stored on our body, ergo fat-soluble vitamins can also be stored within our fatty compounds ( membran e s, tissues). This means that fat soluble vitamins can accumulate in the body to be saved for later use. Fat soluble vitamins exhibit toxicity in overdose Hormone vitamins among the se are: Vitamin D and A

5. Fat-soluble vitamins storage place. Toxicity The vitamins A, D, E, K belong to the fat-soluble vitamins. These are stored in the body for long periods of time and generally pose a greater risk for toxicity when consumed in excess. Significant amounts of fat soluble vitamins can be stored in adipose tissue and the liver . The main sites of storage are also such inner organs kidneys, the muscles, and the brain. Toxicity : Birth defects, Central nervous disorders, Liver abnormalities, Loss of bone density are the side effect of overdose vitamin A and its toxicity.

6. Entry, transport and excretion of fat-soluble vitamins T he fat-soluble vitamins are transported into th e cells of small intestine in micelles . Once inside the intestinal cells, fat-soluble vitamins are packaged with fat and other lipids into a chylomicron ; being too large in diameter, chylomicrons cannot penetrate the blood capillaries. Therefore, the chylomicrons travel through the lymph system to the main blood circulation. Excretion of fat-soluble vitamins normally occurs via gallbladder into the intestine only after their transformation during metabolism. But excretion of vitamin A is m ostly through the urine as oxo-retinoic acid ; small amounts in expired air, some in feces.

7. VITAMIN A, retinol, an anticerophthalmic vitamin structure β -ionone ring Side chain from 2 isoprene residues

8. Vitamin A –retinol ( anticerophthalmic vitamin) Vitamin A was discovered in 1909 in fish liver oil Vitamin A is represented by a group of retinoids that include such active forms as retinol, retinal, and retinoic acid. They contain a β -ionone ring with a polyunsaturated tail made up from 2 isoprene residues. Attached at the end of the tail group may be in the form of: alcohol group (retinol), an aldehyde group (retinal), or an acid group (retinoic acid).

9. Retinoids is the term used for the family of vitamin A compounds. Their active forms are present only in animal tissues. Retinol The alcohol form of vitamin A. Retinal The aldehyde form of vitamin A. Retinoic acid The acid form of vitamin A. Retinyl ester The ester form of vitamin A ( retinyl palmitate , retinyl acetate, retinyl phosphate) is stored in the body tissues. Beta-carotene is one of the carotenoid provitamins (precursor) for A vitamin Vitamin A is the name of a group of fat-soluble retinoids, including retinol, retinal, and retinyl esters .

10. Interconversion of Vitamin A Compounds in the organism Retinyl ester Retinol (alcohol form) oxo-Retinoic acid Retinal (aldehyde form)   (in the liver ) Beta-carotene In the eyes (for vision) Vitamin A supports cell growth and differentiation , playing a critical role in the normal formation and maintenance of the heart, lungs, kidneys , and other organs.

11. Absorption & storage 15-15’ dioxygenase of intestinal cells hydrolyze β-carotene to release 2 moles of vitamin A. The various forms of vitamin A are solubilized into micelles in the intestinal lumen and absorbed by duodenal mucosal cells. In intestinal mucosal cells, retinol is incorporated into chylomicrons & transferred to lymph . Vitamin A is taken up from chylomicrons by liver & stored . Most of the body’s vitamin A is stored in the liver in the form of retinyl esters .

12. When required, vitamin A is released from liver and transported by plasma circulation with retinol binding protein or in association with albumin. To enter cells, retinol-protein complex binds to their receptors on cell membrane of peripheral tissues. In our cells, b oth retinyl esters and provitamin A carotenoids are converted to retinol , which is oxidized to retinal and then to retinoic acid .

13. Vitamin A interconversion in the cell & excretion (for excretion ) RA- Retinoic Acid

14. Hormone like effect of vitamin A: After entering the cell, vitamin A binds to the cellular retinol-binding protein(CRBP). Then Retinol Dehydrogenase ( RDH ) converts it to retinol. Under assistance of Retinal Dehydrogenase (RDH) Retinol becomes retinal, then – retinoic acid (RA). (RA) is carried to nucleus & binds to chromatin (DNA) by Cellular Cellular Retinoic Acid Binding Protein I and II ( CRABP ). After this, is stimulates Gene transcription, and by this way - the growth and development of tissues, embryonic development and reproduction . This mechanism of action is similar to hormonal action, which is why vitamin A is referred to as hormone -vitamins Vitamin A belongs to hormone –vitamins.

15. Gene expression by vitamin A

16. Metabolic Functions of Vitamin A The hormone-like action of retinoic acid (the acid form) is essential for growth and development of cells, including bone development . Control of cells differentiation processes. Formation, protection and regeneration of skin and mucous membranes

17. Role of vitamin A in norm Vitamin A is essential for proper bone, teeth, cartilage growth, differentiation, proliferation, regeneration & healing. digestive, respiratory, and urinary tracts mucous membranes Protection against infection.

18. Immunostimulating function Vitamin A is involved in immune function, vision, and cellular communication. Retinol supports reproduction and a healthy immune system in the alcohol form . Increases resistance to infectious diseases. In addition to these critical roles, vitamin A may help prevent cancer .

19. Physiological role of vitamin A Role in reproduction: Promotion of fertility It may also be needed for breast-feeding Vitamin A participates in hematopoiesis (the production of blood cells and platelets) It exposes an antioxidant activity

20. Role in the vision Vitamin A is critical for vision as an essential component of rhodopsin , a protein that absorbs light in the retinal receptors , and because it supports the normal differentiation and functioning of the conjunctival membranes and cornea. Retinal (the aldehyde form) participates in vision . Retinal is an active compound of RHODOPSIN , which is the membrane protein in photoreceptor of retina.

21. Vitamin A in vision acts through g-protein transducin . Alcohol dehydrogenase Cis -trans- isomerase Cis -trans- isomerase 11-cis-retinal 11-cis-retinol Activation of transducin accotiated with opsine Rods and cones of the cornea All-trans-retinal All-trans- reninol Alcohol dehydrogenase

22. Vitamin A deficiency symptoms : Deficiency may be dietary (i.e., intake) or metabolic (i.e., absorption). Cornification of skin and mucous membranes. Hemeralopia (nyctalopia, night blindness) . Xeropthalmia (dryness of the cornea due to blockage of the lacrimal canal ) Keratomalacia (softening and ulceration of the cornea ). Keratomalacia is an eye (ocular) condition, usually affecting both eyes (bilateral), that results from severe deficiency of vitamin A. Retarded maturation of the ova and embryo mortality. Increased risk of infections . Nervous lesions .

23. Hemeralopia ( Nyctalopia ) is very dangerous for drivers Early symptoms of vitamin A deficiency may include poor vision at night or in dim light (night blindness) and extreme dryness of the eyes (!) , i.e., xerophthalmia ), followed by wrinkling, progressive cloudiness, and increasing softening of the corneas (i.e., keratomalacia ).

24. Xeropthalmia & keratomalacia lead to Blindness , if not treated Beginning: Xeropthalmia . With advancing vitamin A deficiency, dry, “foamy,” silver-gray deposits ( Bitot spots) may appear on the delicate membranes covering the whites of the eyes. Finish: Keratomalacia . Without adequate treatment, increasing softening of the corneas ( keratomalacia )may lead to corneal infection, rupture (perforation), and degenerative tissue changes, resulting in blindness.

25. Sources in the nature & bioavailability Vitamin A is found only in feeds of animal origin , e.g. liver, fish oil and high-fat fishmeal Low concentrations are also found in milk and eggs . Feeds of plant origin ( grass, carrots ) contain ß- carotene , a precursor converted in the body to vitamin A. Vitamin A and carotenoids are absorbed in the intestine as micelles, brought into the liver with chylomicrones , where conversion of ß –carotene into 2 molecules of vitamin A occur. Retinol is transported in the blood in associated with retinol-binding protein form

26. Sources of vitamin A Two forms of vitamin A are available in the human diet: preformed vitamin A (retinol and its esterified form, retinyl ester) and provitamin A - carotenoids. Preformed vitamin A is found in foods from animal sources, including dairy products, fish, and meat (especially liver). By far the most important provitamin A carotenoid is beta-carotene; other provitamin A carotenoids are alpha-carotene and beta-cryptoxanthin. Other carotenoids found in food, such as lycopene, lutein, and zeaxanthin, are not converted into vitamin A.

27. Vitamin A food sources

28. Vitamin D, calciferol , an antirachitic vitamin   It is available in 2 forms- Cholecalciferol (vitamin D 3 ) and ergocalcirerol ( vitamin D 2 ) Cholecalciferol is made from 7-dehydrocholesterol in the skin of animals and humans . Ergoalciferol - D2 is obtained artificially by irradiation of ergo- sterol and is called ergocalciferol .

29. Convertion of 7-dehydro-cholesterol to vitamin D 3 ( cholecalciferol ) Cyclopentane perhydrophenantrene fused ring Side chain "broken" ring

30. So called SUNSHINE VITAMIN formation Vitamin D ( calciferol ) is called the “sunshine vitamin” because it is formed by the action of ultraviolet (UV) rays on cholesterol found in the skin.

31. Activation of vitamin D Vitamin D is carried in the bloodstream to the liver by chylomicrones . Whether it is made in the skin or ingested, in hepatocytes (liver cells) cholecalciferol is hydroxylated in the liver to calcidiol . This reaction is catalyzed by the microsomal enzyme vitamin D 25 hydroxylase . Once made, the product is released into the plasma, where it is bound to an α-globulin, vitamin D-binding protein. In the liver it is converted into the prohormone calcidiol , then to hormone calcitriol .

32. Role of VITAMIN D in metabolism By binding to vitamin D- binding protein , a carrier protein in the plasma, calcitriol is transported to various target organs. The circulating calcidiol transferred to the proximal renal tubules can be converted to calcitriol , the biologically active form of vitamin D. Thus, in the kidneys, calcidiol is hydroxylated to calcitriol . This product is a potent ligand of the vitamin D receptor, which mediates most of the physiological actions of this vitamin. Calcitriol exposes the hormonal action . In addition to the kidneys, calcitriol is also synthesized by monocyte -macrophages in the immune system. When synthesized by monocyte -macrophages, calcitriol acts locally as a cytokine, defending the body against microbial invaders by stimulating the innate immune system.

33. Vitamin D raises insulin secretion, supresses gluconeogenesis (need in DM) and angiotensin II (activated in hypertention and COVID action)

34. Benefits of VITAMIN D for the organism VITAMIN D maintains:  Calcium Balance, providing of bones and teeth development. Immunity  Blood Pressure Regulation Cell Differentiation It promotes germ cell production It increases the performance of the immune system, and inhibits auto- immunisation .  

35. Vitamin D main functions: regulation of Ca and phosphorus metabolism Increases excretion of phosphorus by kidneys and lowers excretion of Ca in the urine Raises Ca reabsorption in the kidneys. Raises Ca and phosphorus sedimentation in the bone tissue ( mineralization of bones and teeth) . When overdosed , it also stimulates mineralization of cartilages and other soft tissues Phosphorus : Ca and P ratio is important regulator for vitamin D activation by feed-back mechanism. E.g. r aised in the blood, Calcium lowers levels of vitamin D and impedes calcium absorption.

36. Symptoms of vitamin D deficiency Disorders of calcium and phosphate metabolism. Rickets in children & osteomalacia in adults ( softening of the bones ). Extraction of mineral substances from the bones and teeth. Deformed bones and joints (softening of the bones). Growth disorders. Spontaneous bone fractures, caries . (Poor eggshell stability in the chicken).

37. The main rachitic symptoms the child becomes nervous, sweats, the fontanelles of the skull do not grow together for a long time, the bones of the skull soften, the ribs soften and deform, taking on a keeled shape, the size of the abdomen increases short stature Short stature Abdominal enlargement Rickety rosary Keel-like chest

38. Vitamin D sources

39. DAILY REQUIRMENT of vitamin D Men and women- 0.01 mg –the lowest requirement During pregnancy and lactation– 10-12,5 mcg Infants & Children –0.01 mg Toxicity kidney damage, Nausea, Weakness, Disorientation. Excretion Bile > feces > urine

40. VITAMIN E- tocopherol , an anti sterile vitamine The term “ tocopherol ” is derived from the word toco meaning “ child birth ” and “ pheros ” meaning “ to bear ”. Vitamin E was discovered 1922 in wheat germ oil. They are naturally occuring anti-oxidants. By this way they play a role of anti-aging factor. α-,β-,γ-, δ - t ocopherols have been obtained from the natural sources.

41. It is yellow oily liquid freely soluble in fat solvent. Vitamin E include both tocopherols and tocotrienols . V itamin E structure : Tocol ring side chain made up from isoprene residues Humidity and long storage have an adverse effect on vitamin E stability and content. Cereals and middlings mainly contain beta-, gamma- and delta- tocopherols (70–90%) with a biological activity significantly lower than that of alpha- tocopherol .

42. Role OF VITAMIN E in the organism Free radicals can expose a negative effect on cells causing oxidative damage that leads to cell aging and eventually to death . Antioxidants, such as vitamin E, prevent cell damage by binding to the free radical and neutralizing them: When vitamin E binds to free radicals, and reduces the production of lipid peroxide radicals from highly unsaturated fatty acids

43. Physiological Role of vitamin E It is a fat stabilizer (protection against oxidation) in animal products (meat, milk, eggs). A diet rich in vitamin E might protect some people against Alzheimer’s disease (Data based on recent population based study of antioxidants). But vitamin E in the form of supplements was not associated with a reduction in the risk of Alzheimer’s disease (Vitamin E should be taken from natural sources ).

44. VITAMIN E is the most powerful natural antioxidant . What does it mean? It is free radical scavenger, Protects double bonds in polyunsaturated fatty acids from oxidation . By this way protects: cell membranes and Low density lipoproteins from oxidation, Prevents rancidity of fats. Vitamin E also plays a role in neurological functions , and Inhibits platelet aggregation . Works in conjunction with selenium

45. Additional functions of vitamin E: Controls the development and function of the gonads. Protection against abortion. Controls metabolism of the hormones via the anterior lobe of the hypophysis Stimulates antibody production, phagocytosis and the bactericide effects of phagocytes.

46. Vitamin E deficiency is artificial, it does not occur in humans As vitamin E exhibits antitoxic effect , and Reduces the incidence of liver necrosis and muscular degeneration , maintains membrane stability , especially of the cardiac and skeletal muscles, ergo in its deficiency are observed: In the muscles, myosin, glycogen, Ca and Mg, phosphorus, creatin sharply decrease. Increased levels of lipids and NaCl in skeletal muscle Dystrophic muscle disorders lead to their decreased mobility.

47. Vitamin E deficiency symptoms Damage to cardiac and skeletal muscles (dystrophy, myopathy ) Sudden death through damage to the heart muscle (mulberry heart disease) Liver lesions and changes in fat deposits: liver fatty dystrophy.  Fertility disorders . Hemolytic anemia due to RBC membrane rupture Degeneration of spinal cord

48. Dietary sources of vitamin E: Natural sources and bioavailability  Grass, clover, alfalfa, green meal and uncrushed oilseeds are rich in vitamin E. Green olives almonds bell pepper dried apricots Cold-pressed plant oils red chili powder Cooked spinach avocado papaya greens

49. Daily recommended dose of vitamin E men - 10 – 15 IU (1 IU = 1 mg of tocopherol )  women – 5- 8mg   Children – 8.3mg Infants – 4- 5mg Toxicity   There isn’t any known risk of consuming too much vitamin E from natural food sources. Because vitamin E can act as an anticoagulant and interfere with blood clotting, excess amounts in the body increase the risk of hemorrhage.

50. Interaction of vitamin E with other nutrients Nutrients Synergistic to Vitamin E Selenium : Function closely linked to vitamin E (needed for GSH peroxidase ). Vitamin C : Helps in anti oxidant property.

51. Vitamin K Vitamin K was discovered in 1929 in alfalfa   Natural sources and bioavailability: Vitamin K is a generic term for vitamin K1 ( phylloquinone ), K2 ( menaquinone ) and K3 ( menadione ) . Green plants are rich in vitamin K1, Vitamin K2 is produced by bacteria in the rumen and in the large intestine.

52. Quinone derivatives Vitamin K3 ( menadion , vicasol ) is an industrial form. The fat-soluble forms K1 and K2 can only be absorbed when pancreas lipase and bile acid are secreted. Bile is not necessary for the water-soluble vitamin K3. All three forms serve as a basis for the production of menaquinone-4, which is highly active in the metabolism.

53. VITAMIN K, quinone , an anti – hemorrhagic vitamin. Term Vitamin K implies a group of structurally and physiologically similar natural vitamins ( vitamers ). Vitamin K includes two vitamers : vitamin K 1 ( phylloquinone ) , and vitamin K2 ( menaquinones ). They are fat soluble. Vitamin K3 , water soluble artifical vicasol is also known. needed for synthesis of proteins required for: blood coagulation , binding of calcium in bone and other tissues. In blood coagulation , it is essential for production of prothrombin and other clotting factors.

54. THE CHEMICAL STRUCTURE OF VITAMIN K vitamers Vicasol Side chain made up by 4 isoprene residues Side chain made up by 6,7 or 9 isoprene residues Quinone ring

55. Metabolic functions of VITAMIN K   Production of the calcium transport protein osteocalcin for bone mineralization Vitamin K is a co-factor for the enzyme, γ - glutamate carboxylase . This enzyme is required for the post- translational modification of bone tissue proteins containing glutamic acid. These proteins go through a carboxylation . This reaction alters the structure of bone proteins by converting glutamic acid residues into γ- carbo xyglutamic acid. The functional significance of this change is that γ- carboxyglutamic acid provides a strong binding affinity to calcium .

56. FUNCTIONS OF VITAMIN K  Vitamin K induces synthesis of prothrombin (clotting factor II ) It is also essential for the hepatic synthesis of coagulation factors : VII, IX, X. It increases CLOTTING rate ( prevents hemorrhage) only in cases when there is defective production of prothrombin. Thus, vitamin K provides the blood clotting. Vitamin K is needed for carboxylation of glutamyl (glutamic acid) residue in protein, that provides capture of Ca++

57. Vitamin K deficiency leads to hemorrhage (bleeding & bruising) Vitamin K is naturally produced by the bacteria in the intestines.

58. DAILY REQUIRMENT     men and women – 70 – 140 mcg. children – 35 – 75mcg

59. NATURAL SOURCES OF VITAMIN K Potato, cabbage are rich in vitamin K as well Vitamin K is found in the following foods:  Green leafy vegetables , such as kale, spinach, turnip greens, collards, Swiss chard, mustard greens, parsley, romaine, and green leaf lettuce. Vegetables such as Brussels sprouts, broccoli, cauliflower .

60. Deficiency symptoms Hemorrhages in various tissues and organs. Blood coagulation disorders. Growth disorders. Antagonists Dicoumarol . Coumarin derivatives. Sulphonamides . Mycotoxins . Warfarin

61. Toxicity in vitamin K overdose   Occurs rarely. Vitamin K, excessive amounts can cause the breakdown of red blood cells and liver damage.

62. Vitaminotherapy main rules Each vitamin is useful in treatment of its deficiency or avitaminosis. Some vitamins are used for treatment of symptoms. Majority of vitamins are treatable in polyvitamin complexes Vitamins are included in COVID treatment Avoid overdose of vitamin B6 and fat-soluble vitamins Avoid complex use of vitamins that oppress action of each other