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Physiologicak roles of vitamins

  1. physiological roles of Vitamins Prepared by; Dr. Siham Gritly Dr. Siham Gritly 1
  2. glossary • Vitamin (water soluble vitamin, fat soluble vitamin): an organic substance needed in small amounts for normal body functions that the body cannot synthesize in adequate amounts • enzyme: a protein that is a catalyst • cofactor: a small, inorganic or organic substance that facilitates enzyme action; includes bothorganic coenzymes made from vitamins and inorganic substances such as minerals • Coenzymes are non-protein organic molecules that are mostly derivatives of vitamins soluble in water by phosphorylation; they bind apoenzyme to proteins to produce an active holoenzyme Dr. Siham Gritly 2
  3. • prosthetic group: a cofactor permanently associated with the protein, often covalently bound • holoenzyme: catalytically active enzyme-cofactor complex. • apoenzyme: an enzyme without its cofactor enzymatically inactive protein • FADH2 flavin adenine dinucleotide (reduced form); a molecule, central to metabolism, which carries a pair of electrons only slightly less energetic than those of NADH • NADH nicotinamide adenine dinucleotide (reduced form); a molecule, central to metabolism, which carries a pair of high-energy electrons Dr. Siham Gritly 3
  4. • free radicals: unstable and highly reactive atoms or molecules that have one or more unpaired electrons in the outer orbital • 1,25-dihydroxyvitamin D: vitamin D that is made from the hydroxylation of calcidiol in the kidneys; the biologically active hormone; also called calcitriol or active vitamin D. • 25-hydroxyvitamin D: vitamin D found in the • blood that is made from the hydroxylation of cholecalciferol in the liver; also called calcidiol • acetyl CoA; a 2-carbon compound (acetate, or acetic acid) to which a molecule of CoA is attached. • antioxidant: a substance that signifi cantly decreases the adverse effects of free radicals on normal physiological functions Dr. Siham Gritly 4
  5. Vitamins • Vitamins are organic molecules needed for variety of biological function within the body. • The most important role of the vitamins is to serve as cofactors (co-enzymes) for enzymatic reactions. • protein + coenzyme (vitamin)= enzyme • protein + cofactor (metal ion)= enzyme • the vitamins cannot be synthesized by mammalian cells and, therefore, must be supplied in the diet in small quantities (microgram or milligram per day). Dr. Siham Gritly 5
  6. Coenzyme and vitamins • Most of the B vitamins are coenzymes and are essential in facilitating the transfer of atoms or groups of atoms between molecules in the formation of carbohydrates, fats, and proteins • coenzymes: complex organic molecules that work with enzymes to facilitate the enzymes’ activity. Many coenzymes have B vitamins as part of their structures. Dr. Siham Gritly 6
  7. • coenzymes is to act as transporters of chemical groups from one reactant to another. • Examples include; • - nicotinamide adenine dinucleotide (NAD), which accepts hydrogen (and gives it up in another reaction), • -ATP, which gives up phosphate groups while transferring chemical energy Dr. Siham Gritly 7
  8. The vitamins are of two distinct types, water soluble and fat soluble. Water Soluble Vitamins Fat Soluble Vitamins Thiamin (B1) Vitamin A Riboflavin (B2) Niacin (B3) Vitamin D Pantothenic Acid (B5) Pyridoxal, Pyridoxamine, Vitamin E Pyridoxine (B6) Biotin Vitamin K Cobalamin (B12) Folic Acid Ascorbic Acid Dr. Siham Gritly 8
  9. Water soluble vitamins • -soluble in water, consist of carbon, hydrogen, oxygen nitrogen, sulfur, cobalt, • -deficiency usually occur more than fat soluble vitamins • -Water-soluble vitamins that body cannot store Dr. Siham Gritly 9
  10. • -enter in energy production and in essential enzyme system. They help with release of energy from carbohydrates, proteins, and fats • -activate chemical reaction inside the body and act as coenzymes • -excretion in urine through urination • -the most important water soluble vitamins are B complex and vitamin C Dr. Siham Gritly 10
  11. Thiamine or vitamin B1 • thiamine-sulfur containing water soluble vitamin of B complex, exist in tissues in the active form of Thiamine Pyrophosphate (TPP) • - Thiamine Pyrophosphate (TPP) is essential co-enzyme involve in energy extraction and cellular process in catabolism of sugar and amino acid • -human and other animal obtain it through diet Dr. Siham Gritly 11
  12. • The majority of thiamine in serum is bound to proteins, mainly albumin. • Approximately 90% of total thiamine in blood is in erythrocytes (red blood cell). Dr. Siham Gritly 12
  13. • Thiamin is rapidly converted to its active form, thiamin pyrophosphate, TPP, in the brain and liver by a specific enzyme;- • thiamin diphosphotransferase. • TPP is necessary as a cofactor for the;- • 1-pyruvate dehydrogenase (PDH) and • 2-α-ketoglutarate dehydrogenase catalyzed reactions associated with the TCA cycle • 3-transketolase catalyzed reactions of the pentose phosphate pathway Dr. Siham Gritly 13
  14. Thiamin functions • -the main function of thiamine is its role in metabolic reaction acting as co-enzyme for energy and carbohydrate metabolism • -its deficiency in tissues affect energy metabolism and thus affect nerve and cardiac functions Dr. Siham Gritly 14
  15. TPP is necessary as a cofactor for the important enzyme pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase and transketolase • 1-Pyruvate dehydrogenase is the key enzyme in CHO metabolism to complete oxidation (via the TCA cycle) • TPP participate in catalyzing oxidative decarboxylation of pyruvate, to form acetyl- CoA in citric acid cycle, where a carboxyl group is removed from a compound and released as CO2. Dr. Siham Gritly 15
  16. An example is the conversion of pyruvate to acetyl- CoA, which is irreversible, during CHO metabolism • Oxidative decarboxylation reactions are oxidation reactions in which a carboxylic group is removed, forming CO2 Dr. Siham Gritly 16
  17. • 2-α-ketoglutarate dehydrogenase -thiamine involved in decarboxylation of alph ketoglutrate to succinate in krebs cycle by the emzyme α-ketoglutarate dehydrogenase • -deficiency of thiamine lead to accumulation of pyruvate in the blood thus affect peripheral nervous system and heart Dr. Siham Gritly 17
  18. • 3-transketolase; catalyzed reactions of the pentose phosphate pathway • oxidative phase, NADPH is generated when glucose 6-phosphate is oxidized to ribose 5- phosphate. Dr. Siham Gritly 18
  19. deficiency of thiamin • -two different diseases may result as deficiency of thiamin • 1-Beri Beri (wet and dry beri beri) Usually beri beri diseases result due to long term deficiency and high intake of carbohydrates • -Korsakoff syndrome (psychosis) Dr. Siham Gritly 19
  20. • Wernicke-Korsakoff syndrome; This disease is most commonly found in chronic alcoholics due to their poor dietetic lifestyles. • Wernicke-Korsakoff syndrome is characterized by acute encephalopathy (brain dysfunction) followed by chronic impairment of short-term memory Dr. Siham Gritly 20
  21. • - Wet beriberi is associated with mental confusion, muscular atrophy, edema, tachycardia, caridomegaly and congestive heart failure in addition to peripheral neuropathy (is damage to nerves of the peripheral nervous system • - Dry beriberi is characterized principally by peripheral neuropathy. Muscle become waste and week, difficult walking, patient become bedridden and may die. Dr. Siham Gritly 21
  22. Beriberi is a disease caused by a deficiency of thiamine (vitamin B1) that affects many systems of the body, including the muscles, heart, nerves, and digestive system Dr. Siham Gritly 22
  23. Riboflavin, vitamin B2 • Active form of riboflavin is Riboflavin Phosphate • It is the central component of the cofactor FAD and FMN, and therefore required for energy metabolism • vitamin B2 is required for a wide variety of cellular processes transferring oxygen from plasma to the tissues. • It plays a key role in energy metabolism, and for the metabolism of fats, ketone bodies, carbohydrates and proteins. Dr. Siham Gritly 23
  24. • Vitamin B2, or riboflavin is an intermediary the transfer of electrons in the cellular oxidation-reduction reactions which generate energy from protein, carbohydrate and fat FAD and FMN. • The riboflavin coenzymes are also important for the transformation of vitamin B6 and folic acid into their respective active forms, and for the conversion of tryptophan into niacin. Dr. Siham Gritly 24
  25. • Synthesis of these two cofactors occurs in a two step process. • 1-FMN is synthesized from riboflavin via the ATP-dependent enzyme riboflavin kinase (RFK). • RFK introduces a phosphate group onto the terminal hydroxyl of riboflavin. Dr. Siham Gritly 25
  26. • 2-FMN is then converted to FAD via the attachment of AMP (derived from ATP) though the action of FAD pyrophosphorylase Dr. Siham Gritly 26
  27. Deficiency of riboflavin • In humans, signs and symptoms of riboflavin deficiency • -include cracked and red lips, inflammation of the lining of mouth and tongue, mouth ulcers, cracks at the corners of the mouth (Angular cheilitis), and a sore throat. • -A deficiency may also cause dry and scaling skin, fluid in the mucous membranes, and iron- deficiency anemia. The eyes may also become bloodshot, itchy, watery and sensitive to bright light. Dr. Siham Gritly 27
  28. Riboflavin Deficiency Riboflavin Deficiency Riboflavin Deficiency (Cheilosis) (Glossitis Dr. Siham Gritly 28
  29. Niacin Vitamin B3 nicotinic acid, nicotinamide, niacinamide • Niacin (nicotinic acid and nicotinamide) is also known as vitamin B3. • Both nicotinic acid and nicotinamide can serve as the dietary source of vitamin B3. • Niacin is required for the synthesis of the active forms of vitamin B3, nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+). Dr. Siham Gritly 29
  30. • NADH, NAD+, NADP+ and NADPH which are coenzymes found in all living cells. • NAD+ and NADP+ are oxidizing agents.(loss of electron) • NADH and NADPH are reducing agents.(gain of electron) reactions involved dehydrogenase enzymes electron transport and hydrogen carrier involved in fats, carbohydrates and protein metabolism Dr. Siham Gritly 30
  31. Niacin functions Role of NAD+ in oxidation-reduction reactions 1-reaction of transport hydrogen atom from one part to another, occur in mitochondria and cytoplasm of the cells –oxidative reactions of NAD------NADH *glycolysis -------glyceraldehyde 3P to 1,3 diphosphglycerate *oxidative decarboxylation of pyruvate to lactate Dr. Siham Gritly 31
  32. oxydation of acetyl Co A in TCA cycle -malate to oxaloacetate -glutamate to α ketoglutrate *β oxidation of fatty acid 2-NAD----dehydrogenase for catabolism of vitamin B6 pyridoxal to its excretory product (pyridoxin acid) Dr. Siham Gritly 32
  33. 3-NADPH (reduced form) involved in; Fatty acid synthesis Cholesterol synthesis Deoxy-ribonucleotide molecules (DNA) 4-NADPH--- convert folate to dihydrofolate (DHF) and synthesis of 5 methyl- tetrahydrofolate the active form of folic acid Dr. Siham Gritly 33
  34. niacin deficiency • Severe deficiency of niacin in the diet causes the disease pellagra characterized by three Ds; Diarrhea, loss of fluids Dermatitis, hyperpigmentation, thickening of the skin, inflammation of the mouth and tongue, digestive disturbances, Dementia, (mental symptoms) such as irritability, poor concentration, anxiety, fatigue, restlessness, apathy, a nd depression Dr. Siham Gritly 34
  35. Pellagra niacin deficiency Dr. Siham Gritly 35
  36. Pellagra niacin deficiency Dr. Siham Gritly 36
  37. Pyridoxine vitamin B6 • Pyridoxal, • pyridoxamine • Pyridoxine • are collectively known as vitamin B6. • The three forms equal vital activities in their active forms • found in different types of food such as; Wheat germ, Sunflower seeds, Dry Soybeans, Walnuts, Soybean flour Lentils Brown rice peas Bananas, Chicken, white fish, Potatoes Dr. Siham Gritly 37
  38. • All three compounds are efficiently converted to the biologically active form of vitamin B6, pyridoxal phosphate (PLP). • -pyridoxal phosphate • -pyridoxine phosphate • -pyridoxamine phosphate • This conversion is catalyzed by the ATP requiring enzyme, pyridoxal kinase. • Pyridoxal kinase requires zinc for full activity thus making it a metaloenzyme. Dr. Siham Gritly 38
  39. • Pyridoxal phosphate functions as a cofactor in enzymes involved in transamination reactions required for the synthesis and catabolism of the amino acids • Act as co-enzyme needed in amino acid metabolism such as conversion of essential amino acid tryptophan to vitamin niacin Dr. Siham Gritly 39
  40. • Also it function in glycogenolysis as a cofactor for glycogen phosphorylase • Vitamin B6 is involved in over 100 metabolic reactions in the body, including the production of energy and hemoglobin, a protein in red blood cells. Intakes below the DRI can hurt performance. • Deficiencies of vitamin B6 are rare and usually are related to an overall deficiency of all the B-complex vitamins Dr. Siham Gritly 40
  41. • Factors which reduce Vitamin B6 absorption • Exposure of Vitamin B6 containing foods to ultraviolet light • Cooking • Exposure to alkaline pH • Food processing destroys up to 90% of Vitamin B6 content in food Dr. Siham Gritly 41
  42. • Factors which increase Vitamin B6 excretion • Smoking • Excess alcohol • Excessive tea /coffee caffeinated drinks consumption • Use of hormonal contraception • Use of drugs such as diuretics, • Excessive protein consumption Dr. Siham Gritly 42
  43. Pantothenic acid • Pantothenic acid is used in the synthesis of co- enzyme A (CoA). • This coenzyme is formed when the vitamin combines with a derivative of ADP and the amino acid cysteine. • Coenzyme A may act as an acyl group carrier to form acetyl-CoA and other related compounds; this is a way to transport carbon atoms within the cell. Dr. Siham Gritly 43
  44. • CoA is also important in the biosynthesis of many important compounds such as fatty acids, cholesterol. • CoA is important in energy metabolism for pyruvate to enter the Kerbs cycle or tricarboxylic acid cycle (TCA cycle) as acetyl- CoA, • and for α-ketoglutarate to be transformed to succinyl-CoA in the cycle. Dr. Siham Gritly 44
  45. Deficiency of Pantothenic Acid • deficiency of pantothenic acid in rats leads to elevated serum concentrations of triglycerides and non-esterified fatty acids, reflecting impaired β- oxidation. • with B-oxidation would have an effect on fat use. Co-A is also necessary in CHO metabolism, as it is a part of acetyl-CoA Dr. Siham Gritly 45
  46. Folic acid (pteroylglutamic acid) • The folates are a group of heterocyclic compounds consisting of a pteridine ring structure linked to para- aminobenzoic acid (PABA) that forms pteroic acid. • Pteridine is a group of organic compounds having two fused six-member rings each containing two nitrogen atoms and four carbon atoms. • One of the rings is a pyrimidine, the other a pyrazine. Dr. Siham Gritly 46
  47. Folic acid (pteroylglutamic acid) is composed of three large sub- components. 1-pteridine ring,2- para-amino benzoic acid, and 3- glutamic acid. Glutamic acid is an amino acid that the body can actually synthesize by itself and is found in proteins. Folic acid gets its name from the Latin word folium meaning "leaf", since it's found in many leafy plants. Dr. Siham Gritly 47
  48. • The number of glutamate molecules affects the absorption and metabolism of folate or folic acid in the body. Dr. Siham Gritly 48
  49. active form of folic acid is tetrahydrofolate Chemical structure of THF. The N5 and N10-nitrogen atoms that can carry one-carbon functional groups Dr. Siham Gritly 49
  50. Pteroylglutamate (folic acid) Polyglutamate is the storage form of folic acid in the liver • Folic acid is reduced within cells (principally the liver where it is stored) to; tetrahydrofolate (THF also H4folate) through the action of dihydrofolate reductase (DHFR), an NADPH-requiring enzyme. • When stored in the liver or ingested folic acid exists in a polyglutamate form Dr. Siham Gritly 50
  51. • Deficiency causes megaloblastic anemia as for vitamin B12 deficiency. • The inability to synthesize DNA during erythrocyte maturation leads to abnormally large erythrocytes termed macrocytic anemia • Folic acid is important in preventing neuraltube defects (NTDs) in the developing human fetus. Dr. Siham Gritly 51
  52. megaloblastic macrocytic anemia Dr. Siham Gritly 52
  53. Vitamin B12 cyanocobalamin • Vitamin B12 is the name for a class of related compounds that have the vitamin activity. These compounds contain the rare element cobalt. • Humans can not synthesis B12 and must obtain it from diet. Enzymes that catalyze certain rearrangement reaction required B12 or its derivatives. • Vitamin B12 is synthesized exclusively by microorganisms and is found in the liver of animals bound to protein as methycobalamin or 5'-deoxyadenosylcobalamin. Dr. Siham Gritly 53
  54. • The vitamin must be hydrolyzed from protein in order to be active. • Hydrolysis occurs in the stomach by gastric acids or the intestines by trypsin following consumption of animal meat. • The vitamin is then bound by intrinsic factor, a protein secreted by parietal cells of the stomach, and carried to the ileum where it is absorbed. • Following absorption the vitamin is transported to the liver in the blood bound to transcobalamin II. Dr. Siham Gritly 54
  55. • Vitamin B12 is involved in a number of body processes, but is mainly; • formation to red blood cell production, • nervous system function, • sperm production, • normal growth • the proper function of the immune system. Dr. Siham Gritly 55
  56. There are only two clinically significant reactions in the body that require vitamin B12 as a cofactor. • 1- During the catabolism of fatty acids with an odd number of carbon atoms and the amino acids valine, isoleucine and threonine the resultant propionyl-CoA is converted to succinyl-CoA for oxidation in the TCA cycle. • One of the enzymes in this pathway, methylmalonyl-CoA mutase, requires vitamin B12 as a cofactor in the conversion of methylmalonyl-CoA to succinyl-CoA. • The 5'-deoxyadenosine derivative of cobalamin is required for this reaction. Dr. Siham Gritly 56
  57. • 2-The second reaction requiring vitamin B12 catalyzes the conversion of homocysteine to methionine and is catalyzed by methionine synthase. • This reaction results in the transfer of the methyl group from N5-methyltetrahydrofolate to hydroxycobalamin generating tetrahydrofolate (THF) and methylcobalamin during the process of the conversion Dr. Siham Gritly 57
  58. Deficiencies of B12 Pernicious anemia is a megaloblastic anemia resulting from vitamin B12 deficiency • The liver can store up to six years vitamin B12, therefore deficiencies in this vitamin are rare. • Pernicious anemia is a megaloblastic anemia resulting from vitamin B12 deficiency that develops as a result a lack of intrinsic factor in the stomach leading to malabsorption of the vitamin. Dr. Siham Gritly 58
  59. • Pernicious anemia characterized by abnormally large and immature red blood cells. • Other symptoms include muscle weakness and irreversible neurological damage • The anemia results from impaired DNA synthesis due to a block in purines and thymidine biothynthesis. Dr. Siham Gritly 59
  60. Biotin • Biotin, one of the water soluble B- vitamins, occurs in 8 different forms but only one of these, D-biotin, is found in nature and has full vitamin activity • It is water soluble and important in the metabolism of fatty acids and the amino acid Leucine Dr. Siham Gritly 60
  61. • Biotin in its coenzyme form participates in numerous reactions involved in the metabolism of fat and CHO • involved in carboxylation reactions, e.g. acetyl- CoA carboxylase and pyruvate carboxylase. • participates in the entry of certain carbon skeletons from amino acids into the energy- yielding pathways, as well as in DNA synthesis. Dr. Siham Gritly 61
  62. • Biotin is found in numerous foods and also is synthesized by intestinal bacteria and as such deficiencies of the vitamin are rare. • Deficiencies are generally seen only after long antibiotic therapies which deplete the intestinal fauna or following excessive consumption of raw eggs. • The latter is due to the affinity of the egg white protein, avidin, for biotin preventing intestinal absorption of the biotin. Dr. Siham Gritly 62
  63. Deficiency is rare, but can result in:Anorexia Nausea Vomiting Dermatitis • Symptoms that may appear if biotin is deficient are extreme exhaustion, drowsiness, muscle pain, loss of appetite, depression, and grayish skin color. • Some of the richest sources of biotin are tomatoes, romaine lettuce, and carrots. Additional sources include onions, cabbage, cucumber, cauliflower, mushroo ms, peanuts, almonds, walnuts, oat meal, bananas, raspberries, strawberries, soy, egg yolk, and cow and goat milk. Dr. Siham Gritly 63
  64. Vitamin C Ascorbic Acid Main physiological roles of vitamin C • Vital component of all body cells • Essential for manufacture of collagen, needed for healthy connective tissue, skin, bones and vascular system • Powerful Antioxidant • Stimulates white blood cells and antibody production • Required for proper wound healing and tissue regeneration Dr. Siham Gritly 64
  65. • Assists iron absorption • powerful effects on the production of important chemicals for the control of hormones and brain function. • plays a vital role in the immune system • It is a key component of collagen • Vitamin C also helps to benefit the skin, teeth, and bones. Dr. Siham Gritly 65
  66. • Deficiency leads to a disease called Scurvy. • Scurvy is a disease that affects the blood vessels, skin, and the body’s healing process, resulting in anemia, hemorrhaging of the skin, and gum disease (gingivitis). • Vitamin C is found in most plants and animals Dr. Siham Gritly 66
  67. • People requiring additional Vitamin C. • some specific groups who are likely to benefit more ; • People with heart disease (angina, heart attack, "hardened arteries", coronary artery disease, other vascular disease, high blood pressure) • Diabetics • Those with poorly healing wounds (such as leg ulcers) • People with skin problems Dr. Siham Gritly 67
  68. Examples of Coenzymes and Vitamins reference; Cooper GM; The Central Role of Enzymes as BiologicalCatalysts The Cell: A Molecular Approach. 2nd edition Coenzyme Related vitamin Chemical reaction NAD+, NADP+ Niacin Oxidation-reduction FAD Riboflavin (B2) Oxidation-reduction Thiamine Thiamine (B1) Aldehyde group pyrophosphate transfer Coenzyme A Pantothenate Acyl group transfer Tetrahydrofolate Folate Transfer of one- carbon groups Biotin Biotin Carboxylation Pyridoxal Pyridoxal (B6) Transamination phosphate Dr. Siham Gritly 68
  69. Fat soluble vitamins • Fat soluble vitamins dissolve within the body’s fat cells and are usually found in fats and fatty foods. • If they are not needed immediately, the body will store fat soluble vitamins for later use in the liver and fatty tissues • fat soluble vitamins do not need to be consumed as frequently as water soluble vitamins to ensure proper functioning of the body’s cells. Dr. Siham Gritly 69
  70. Vitamin A • Vitamin A consists of three biologically active molecules, • 1-retinol, (hydroxyl) involved in vision • 2- retinal (aldehyde) involved in vision • 3-retinoic acid. (carboxyl) • Importance for cellular differentiation (regulate gene expression) • Each of these compounds are derived from the plant precursor molecule, β-carotene (a member of a family of molecules known as carotenoids). Dr. Siham Gritly 70
  71. • Beta-carotene, which consists of two molecules of retinal linked at their aldehyde ends, is also referred to as the provitamin form of vitamin A. • Vitamin A is found in dark green and yellow vegetables and yellow fruits, such as broccoli, spinach, turnip greens, carrots, squash, sweet potatoes, pumpkin, cantaloupe, and apricots, and in animal sources such as liver, milk, butter, cheese, and whole eggs. Dr. Siham Gritly 71
  72. Absorption, transport and storage • Ingested β-carotene is cleaved in the lumen of the intestine by β-carotene dioxygenase to yield retinal. • Retinal is reduced to retinol by retinaldehyde reductase, an NADPH requiring enzyme within the intestines. • Retinol is esterified to palmitic acid and delivered to the blood via chylomicrons. The uptake of chylomicron by the liver results in delivery of retinol to this organ for storage as a lipid ester within lipocytes (adipose tissues). Dr. Siham Gritly 72
  73. • Transport of retinol from the liver to extrahepatic tissues occurs by binding of hydrolyzed retinol to aporetinol binding protein (RBP). • the retinol-RBP complex is then transported to the cell surface within the Golgi and secreted. Within extrahepatic tissues retinol is bound to cellular retinol binding protein (CRBP). • Plasma transport of retinoic acid is accomplished by binding to albumin Dr. Siham Gritly 73
  74. Vitamin A functioning as vitamin and hormone • retinol and retinoic acid with in the cell bind to specific receptor present in the nucleolus of tissues • This receptor-vitamin complex interact with several genes that involved in growth and cell differentiation thus affect expression of genes • cell differentiation is the process by which immature cells develop specific functions different from those of the original that are characteristic of their mature cell type. Dr. Siham Gritly 74
  75. Vision and Vitamin A • the process of vitamin A in vision known as Rhodopsin cycle or Ward’s visual cycle the • Photoreception in the eye is the function of two specialized cell types located in the retina; • Rods • Cones • Both rod and cone cells located in the retina contain a photoreceptor pigment in their membranes and vitamin A is a component of these pigments Dr. Siham Gritly 75
  76. • the rod;- The opsin of rod cells is called Rhodopsin (visual purple) consist of 11-cis retinal bound to protein opsin (vision in dim light) • Rhodopsin absorbs light, 11-cis retinal is converted to all trans retinal • The isomerization act on the conformation change in the protein opsin • This process lead to generate nerve impulse that transmitted to brain through the optic nerve Dr. Siham Gritly 76
  77. • This is followed by dissociation of the trans retinal from opsin • The trans retinal is immediately isomerised by the enzyme isomerase to 11-cis retinal • 11-cis retinal combines with opsin to regenerate rhodopsin and complete the vision cycle Dr. Siham Gritly 77
  78. • cone cells, contain colour pigments, *porphyropsin (red) • *Iodopsin (green) • *Cyanopsin (blue) • The pigments are converted to trans retinal and the protein opsin is released • The reaction stimulate the nerve impulse thus the brain red the colour Dr. Siham Gritly 78
  79. Dr. Siham Gritly 79
  80. Vitamin A Deficiency • Vitamin A is stored in the liver and deficiency of the vitamin occurs only after prolonged lack of dietary intake. • The earliest symptoms of vitamin A deficiency are night blindness. • Additional early symptoms include follicular hyperkeratinosis, increased susceptibility to infection and cancer and anemia equivalent to iron deficient anemia. • Prolonged lack of vitamin A leads to deterioration of the eye tissue through progressive keratinization of the cornea, a condition known as xerophthalmia. Dr. Siham Gritly 80
  81. The earliest symptoms of vitamin A deficiency ;- *impaired dark adaptation –night blindness (nyctalopia) *poor vision in dim light *xerophthalmia The first stage of xerophthalmia is conjunctival xerosis Later Bitot’s spots form (keratinization of epithelial cells) A deficiency progresses degenerative changes of retina occurs (keratomalcia) Dr. Siham Gritly 81
  82. keratomalcia Softening and drying and ulceration of the cornea resulting from vitamin A deficiency developed in the cornea that lead to blindness Dr. Siham Gritly 82
  83. Xerophthalmia Xerophthalmia is a severe drying of the eye surface caused by a malfunction of the tear glands. it occurs most commonly because of decreased intake or absorption of vitamin A. Symptoms include night blindness and eye irritationthe eyes being very dry, there is a loss of luster on their surface . Ulceration and necrosis developed in the cornea that lead to blindness Dr. Siham Gritly 83
  84. Vitamin D cholecalciferol • Vitamin D is known as the sunshine vitamin because exposure to sunlight prompt the body’s cells to start producing it. • Vitamin D2 functions as a steroid hormone and vitamin • regulate calcium and phosphorous homeostasis • dairy products (such as eggs, milk and butter), fatty fish and fish oils are all good sources of vitamin D. Dr. Siham Gritly 84
  85. Vitamin D comes in many forms, but the two most important in the diet arel • 1-plant sterol ergosterol which isolated from plant and by commercial irradiation light UV converted to vitamin D2 or ergocalciferol not found in human tissues • 2-animal sources or naturally produced called vitamin D3 or cholecalciferol. Dr. Siham Gritly 85
  86. Formation of vitamin D3 in the skin • The naturally found vitamin D3 cholecalciferol is the form obtained either from animal sources or made in the skin by the action of ultraviolet light from the sun on 7-dehydrocholesterol • 7-dehydrocholesterol found in animal tissues synthesized in the sebaceous glands of the skin and secreted into the skin surface • During exposure to sunlight 7-dehydrocholesterol forming pre-cholecalcefirol (previtamin D3) Dr. Siham Gritly 86
  87. activation of vitamin D must be achieved through; • 1-Liver • 2-kidneys • In the Liver;- cholecalciferol fuses into the blood carried by D-binding protein (DBP) known as transcalciferin to the liver • By the action of liver enzyme 25-hydroxylase hydroxylate cholecaciferol at carbon 25 to form 25- OH cholecalciferol/D3 • The activity of this enzyme related to the concentration of vitamin D • 25-hydroxylase also found in lungs, intestine and Dr. Siham Gritly 87 kidneys
  88. • In the kidneys;-a second hydroxylation of 25-OH D3 (25-hydroxylcalcefirol) occur at position 1 • by the action of enzyme;- • 1-hydroxylase, 25-cholecalsiferol hydrolyized to 1,25-(OH)2 cholecalecalciferol or known as (calcitriol ) the active form of vitamin D • By the transporter DBP which is the major protein in the blood transported the active form calcitriol (1,25-(OH)2 cholecalciferol) to the target tissues Dr. Siham Gritly 88
  89. • Active form of the hormone The biologically active form of the hormone is; 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3, also called 1,25-dihydroxycholecalciferol or calcitriol). Dr. Siham Gritly 89
  90. • The activity of 1-hydroxylase is influenced by • -parathyroid hormone • -low plasma concentration • -The concentration of 1,25 hydoxycholecaciferol- high concentration inhibit the enzyme activity,- low concentration stimulate it • Low intake of phosphours Dr. Siham Gritly 90
  91. • 25-(OH)D3 can also be hydroxylated at the 24 position by a specific D3-24-hydroxylase in the kidneys, intestine, placenta and cartilage Dr. Siham Gritly 91
  92. 1,25-dihydroxcholecaliciferol D3 formation Tissue cholesterol ↓ Sun ↓ 7-dehydrocholesterol Plasma Cholecaliciferol D3 ↓ liver 25-hydroxycholecaliciferol ↓ kidneys 1,25-dihydroxycholecaliciferol → target tissue Dr. Siham Gritly 92
  93. deficiency results in harmful changes in bone, a condition known as rickets in children and osteomalacia in adults. Vitamin D–Deficiency Symptoms—Bowed Legs and Beaded Ribs of Rickets Dr. Siham Gritly 93
  94. • Osteoporosis; Any failure to synthesize adequate vitamin D or obtain enough from foods sets the stage for a loss of calcium from the bones, which can result in fractures. reduced bone density. Dr. Siham Gritly 94
  95. Dr. Siham Gritly 95
  96. Vitamin E tocopherol protect against oxidative damage. • Vitamin E is an antioxidant a substance that that stops chain reactions caused by free radicals that can damage cells and affect its normal physiological function . • free radicals: is an unstable and highly reactive atoms or molecules that have one or more unpaired electrons in the outer orbital • Vitamin E acts primarily in lipid-rich areas of the body, where free radicals can initiate a chain of reactions known as peroxidation. Dr. Siham Gritly 96
  97. • peroxidation is a type of reaction in which oxygen atoms are formed leading to the production of peroxides. • It is stimulated in the body by certain toxins and infections • Lipid peroxidation reactions break apart fatty acids and create free radicals called lipid peroxyl radicals (also called reactive oxygen species because they contain oxygen radicals). Dr. Siham Gritly 97
  98. • The most concern free radicals in biological systems are derived from oxygen, Example of free radicals;- Superoxide radical (O2.- ), Hydrogen peroxide (H2O2), Hydroxyl radical (.OH) and others such as Nitric oxide (.NO) and others • Read more about free radicals Dr. Siham Gritly 98
  99. Dr. Siham Gritly 99
  100. Vitamin K phylloquinone • The K vitamins exist naturally as;- • K1 (phylloquinone) in green vegetables • K2 (menaquinone) produced by intestinal bacteria • K3 is synthetic menadione. • Vitamin K can be synthesized by bacteria in the intestines. • Vitamin K is needed for the process of clotting of blood and Ca2+ binding. • Vitamin K is needed for catalyzing the carboxylation of the γ-carbon of the glutamate side chain in proteins. Dr. Siham Gritly 100
  101. • Vitamin K’s main function is to help the blood clot but it also assists with calcium retention in the body. • Vitamin K contributes to the body’s blood- clotting ability by facilitating the conversion of precursor proteins, such as prothrombin, to active clotting factors thrombin that promote blood coagulation. Dr. Siham Gritly 101
  102. • Green leafy vegetables (such as spinach, broccoli and cabbage) are rich in vitamin K but eggs and milk also contain lower levels of the vitamin. • Deficiency can be very serious and cause heavy, uncontrolled bleeding in multiple areas of the body. • consuming too much vitamin K can damage both blood cells and liver. Dr. Siham Gritly 102
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  104. References • Murry K. Robert, Granner K. daryl, Mayes A. peter, Rodwell W. Victor (1999). Harpers Biochemistry. Appleton and Lange , twent fifth edition • Campbell, Neil A.; Brad Williamson; Robin J. Heyden (2006). Biology: Exploring Life. Boston, Massachusetts: Pearson Prentice Hall • A. Burtis, Edward R. Ashwood, Norbert W. Tietz (2000), Tietz fundamentals of clinical chemistry • Maton, Anthea; Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David LaHart, Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. pp. 52–59 • Maitland, Jr Jones (1998). Organic Chemistry. W W Norton & Co Inc (Np). p. 139. ISBN 0-393-97378-6. • Nelson DL, Cox MM (2005). Lehninger's Principles of Biochemistry (4th ed.). New York, New York: W. H. Freeman and Company. • Matthews, C. E.; K. E. Van Holde; K. G. Ahern (1999) Biochemistry. 3rd edition. Benjamin Cummings. • Dr. Siham Gritly 104
  105. D. Voet, J. G. Voet, Biochemistry, second edition ed., John Wiley & • Sons, New York, 1995 • Sareen Gropper, Jack Smith and James Groff, Advanced Nutrition and Human Metabolism, fifth ed. WADSWORTH • Melvin H Williams 2010; Nutrition for Health, Fitness and Sport. 9th ed, McGraw Hill • • Heymsfield, SB.; Baumgartner N.; Richard and Sheau-Fang P. 1999. Modern Nutrition in Health and Disease; Shils E Maurice, Olson A. James, Shike Moshe and Ross A. Catharine eds. 9th edition • Guyton, C. Arthur. 1985. Textbook of Medical Physiology. 6th edition, W.B. Company • Lehninger. Principles of bochemistry. by Nelson and Cox, 5th Edition; W.H. Freeman and Company • Emsley, John (2011). Nature's Building Blocks: An A-Z Guide to the Elements (New ed.). New York, NY: Oxford University Press. ISBN 978-0-19-960563-7. • Koppenol, W. H. (2002). "Naming of New Elements (IUPAC Recommendations 2002)" (PDF). Pure and Applied Chemistry 74 (5): 787–791. doi:10.1351/pac200274050787. • Dr. Siham Gritly 105