7 vitamins and cofactors


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7 vitamins and cofactors

  1. 1. Principle of Biochemistry7-Vitamins and Cofactors Course code: HFB324 Credit hours: 3 hours Dr. Siham Gritly Dr. Siham Gritly 1
  2. 2. Lecture content• Vitamins: Definition, classification, requirements and chemical properties. Importance of vitamins to biological processes of the living body.• vitamins deficiencies. Dr. Siham Gritly 2
  3. 3. • 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 3
  4. 4. • 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 4
  5. 5. • 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. Dr. Siham Gritly 5
  6. 6. • antioxidant: a substance that signifi cantly decreases the adverse effects of free radicals on normal physiological functions Dr. Siham Gritly 6
  7. 7. Vitamins• Vitamins are organic molecules needed for variety of biological function within the body.• The most important function 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 7
  8. 8. 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.• 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 8
  9. 9. The vitamins are of two distinct types, water soluble and fat soluble.Water Soluble Vitamins Fat Soluble VitaminsThiamin (B1) Vitamin ARiboflavin (B2)Niacin (B3) Vitamin DPantothenic Acid (B5)Pyridoxal, Pyridoxamine, Vitamin EPyridoxine (B6)Biotin Vitamin KCobalamin (B12)Folic AcidAscorbic Acid Dr. Siham Gritly 9
  10. 10. 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 10
  11. 11. • -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 11
  12. 12. 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 12
  13. 13. • 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 13
  14. 14. Thiamin chemical structure Thiamin is derived from a substitutedaminopyrimidine ring and a thiazole ring withmethyl and hydroxyethyl side chains linked by a methylene bridge. C12 H17N4OS Dr. Siham Gritly 14
  15. 15. Thiamin pyrophosphate the active form of vitaminB1 A thiazole ring is found naturally in thiamin Thiazole is a heterocyclic compound featuring both anitrogen atom and sulfur atom as part of the aromaticfive-membered ring. a thiazole ring stabilizes chargeand electron transfer Dr. Siham Gritly 15
  16. 16. • 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 16
  17. 17. 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 17
  18. 18. 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 18
  19. 19. 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 19
  20. 20. • 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 20
  21. 21. • 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 21
  22. 22. 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 22
  23. 23. • 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• - 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 23
  24. 24. 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 24
  25. 25. • 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. 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 25
  26. 26. Riboflavin structure Dr. Siham Gritly 26
  27. 27. Structure of FADRiboflavin is the precursor for the coenzymes, flavinmononucleotide (FMN) and flavin adenine dinucleotide(FAD), used to oxidized substrates.FAD contains riboflavin and adenine. Dr. Siham Gritly 27
  28. 28. The enzymes that require FMN or FAD as cofactors aretermed flavoproteins. During the enzymatic reactions involving theflavoproteins the reduced forms of FMN and FAD areformed, FMNH2 and FADH2, respectively. The hydrogens of FADH2 are on nitrogen 1 and 5 Dr. Siham Gritly 28
  29. 29. • 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 29
  30. 30. • 2-FMN is then converted to FAD via the attachment of AMP (derived from ATP) though the action of FAD pyrophosphorylase Dr. Siham Gritly 30
  31. 31. 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 31
  32. 32. Riboflavin DeficiencyRiboflavin Deficiency Riboflavin Deficiency(Cheilosis) (Glossitis Dr. Siham Gritly 32
  33. 33. Niacin Vitamin B3nicotinic 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 33
  34. 34. Nicotinic acidformula C5H4NCO2H Dr. Siham Gritly 34
  35. 35. Dr. Siham Gritly 35
  36. 36. • 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) Dr. Siham Gritly 36
  37. 37. Important co-enzymesNiacin is the main components of important two Co- enzymes1-nicotin-amide Dinucleotide (NAD)2-nicotin-amide Adenin DinucleotideAct as co-enzyme for reactions involved dehydrogenase enzymesMain function act as electron transport and hydrogen carrier involved in fats, carbohydrates and protein metabolism Dr. Siham Gritly 37
  38. 38. nicotinamide adenine dinucleotide (NAD+) NAD+ is capable of carrying and transferringelectrons and functions as oxidizing agent in redox reactions Dr. Siham Gritly 38
  39. 39. Oxidoreduction: Pyridine nucleotide coenzymes (NAD+/NADP+) (Vitamin B3, Niacin) NAD+/NADH; NADP+/NADPH Dr. Siham Gritly 39
  40. 40. Niacin functions Role of NAD+ in oxidation-reduction reactions1-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 40
  41. 41. oxydation of acetyl Co A in TCA cycle-malate to oxaloacetate-glutamate to α ketoglutrate*β oxidation of fatty acid2-NAD----dehydrogenase for catabolism of vitamin B6 pyridoxal to its excretory product (pyridoxin acid) Dr. Siham Gritly 41
  42. 42. 3-NADPH (reduced form) involved in;Fatty acid synthesisCholesterol synthesisDeoxy-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 42
  43. 43. niacin deficiency• Severe deficiency of niacin in the diet causes the disease pellagra characterized by three Ds;Diarrhea, loss of fluidsDermatitis, 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 43
  44. 44. pellagra Dr. Siham Gritly 44
  45. 45. Pyridoxine vitamin B6• Pyridoxal,• pyridoxamine• Pyridoxine• are collectively known as vitamin B6.• The three forms equal vital activities in their active forms Dr. Siham Gritly 45
  46. 46. • 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 46
  47. 47. Pyridoxine structure It is based on a pyridine ring, withhydroxyl, methyl, and hydroxymethyl Dr. Siham Gritly 47
  48. 48. Pyridoxal Dr. Siham Gritly 48
  49. 49. Pyridoxamine Dr. Siham Gritly 49
  50. 50. Pyridoxal phosphate; the active form of B6Vitamin B6 is precursor to coenzyme pyridoxal phosphate (PLP) which is required in certain transformation of amino acids including transamination, deamination, and decarboxylation. Dr. Siham Gritly 50
  51. 51. • 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 51
  52. 52. • 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 52
  53. 53. 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 53
  54. 54. • 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 54
  55. 55. Co AA coenzyme is a small, organic, non-protein molecules that carries chemical groups between enzymes Dr. Siham Gritly 55
  56. 56. Acetyle co A Acetyl –contain methyl group bonded to carbonyl The carbonyl center of an acyl radical has onenonbonded electron with which it forms a chemical bond to the remainder R of the molecule. Dr. Siham Gritly 56
  57. 57. 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 57
  58. 58. Folic 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 58
  59. 59. • Pyrazine, a group of organic compounds having a six-member ring in which the first and fourth atoms are nitrogen and the rest are carbon pyrimidine, and pyrazine Dr. Siham Gritly 59
  60. 60. • The chemical structures of folic acid consist of three ringed structures plus one or more molecules of the amino acid glutamate (or glutamic acid). The number of glutamate molecules affects the absorption and metabolism of folate or folic acid in the body. Dr. Siham Gritly 60
  61. 61. active form of folic acid is tetrahydrofolateChemical structure of THF. The N5 and N10-nitrogen atoms that can carry one-carbon functional groups Dr. Siham Gritly 61
  62. 62. Folic acid structurepositions 7 and 8 carry hydrogens in dihydrofolate (DHF)positions 5–8 carry hydrogens in tetrahydrofolate (THF) Dr. Siham Gritly 62
  63. 63. • 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• Polyglutamate is the storage form of folic acid in the liver Dr. Siham Gritly 63
  64. 64. • 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 64
  65. 65. 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 65
  66. 66. • 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 digestion 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 66
  67. 67. 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 67
  68. 68. • 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 68
  69. 69. Pyrrole is a heterocyclic aromatic organic compound, a five- membered ring with the formula C4H4NH Dr. Siham Gritly 69
  70. 70. Vitamin B12 is composed of a complex tetrapyrrol ring structure (corrin ring) and a cobalt ion in the center. Tetrapyrroles are compounds containing four pyrrole rings Dr. Siham Gritly 70
  71. 71. Dr. Siham Gritly 71
  72. 72. Deficiencies of B12• 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.• The anemia results from impaired DNA synthesis due to a block in purines and thymidine biothynthesis. Dr. Siham Gritly 72
  73. 73. • Pernicious anemia: a blood disorder that reflects a vitamin B12 deficiency caused by lack of intrinsic factor and characterized by abnormally large and immature red blood cells. Other symptoms include muscle weakness and irreversible neurological damage Dr. Siham Gritly 73
  74. 74. 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• 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. Dr. Siham Gritly 74
  75. 75. • 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 75
  76. 76. Biotin structure Dr. Siham Gritly 76
  77. 77. • 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 77
  78. 78. Deficiency is rare, but can result in:Anorexia NauseaVomiting 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 78
  79. 79. Vitamin C Ascorbic Acid• Vitamin C is found in most plants and animals• it is an essential in many biosynthetic pathways such as synthesizing collagen.• Deficiency leads to a disease called Scurvy.• Vitamin C helps regulate the immune system and relieve pain caused by tired muscles.• It also is needed in the manufacture of collagen and norepinephrine.• Vitamin C is also an antioxidant which can enhance the immune system by stimulating white blood cells in the body.• Vitamin C also helps to benefit the skin, teeth, and bones. Dr. Siham Gritly 79
  80. 80. Ascorbic Acid structure Dr. Siham Gritly 80
  81. 81. Examples of Coenzymes and Vitamins reference; Cooper GM; The Central Role of Enzymes asBiologicalCatalysts The Cell: A Molecular Approach. 2nd editionCoenzyme Related vitamin Chemical reactionNAD+, NADP+ Niacin Oxidation-reductionFAD Riboflavin (B2) Oxidation-reductionThiamine Thiamine (B1) Aldehyde grouppyrophosphate transferCoenzyme A Pantothenate Acyl group transferTetrahydrofolate Folate Transfer of one- carbon groupsBiotin Biotin CarboxylationPyridoxal Pyridoxal (B6) Transaminationphosphate Dr. Siham Gritly 81
  82. 82. 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 82
  83. 83. 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) 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 83
  84. 84. • 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 84
  85. 85. Structure of vitamin A consist of a single6-membered ring to which is attached an 11-carbon side chain Beta-carotene consist of two molecules of retinal linked at their aldehyde ends Dr. Siham Gritly 85
  86. 86. 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 86
  87. 87. • 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 87
  88. 88. 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 88
  89. 89. 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 89
  90. 90. • 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 90
  91. 91. • 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 91
  92. 92. • 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 92
  93. 93. cis-retinal, the hydrogens (light gray in the molecular model onthe left) are on the same side of the double bond (yellow in themolecular model). In the trans-retinal, the hydrogens are onopposite sides of the double bond. In fact, all of the doublebonds are in the trans-configuration in this isomer: thehydrogens, or hydrogen and -CH3, are always on opposite sidesof the double bonds Dr. Siham Gritly 93
  94. 94. Dr. Siham Gritly 94
  95. 95. 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 95
  96. 96. The earliest symptoms of vitamin A deficiency ;-*impaired dark adaptation –night blindness (nyctalopia)*poor vision in dim light*xerophthalmiaThe first stage of xerophthalmia is conjunctival xerosisLater Bitot’s spots form (keratinization of epithelial cells)A deficiency progresses degenerative changes of retina occurs (keratomalcia)Ulceration and necrosis developed in the cornea that lead to blindness Dr. Siham Gritly 96
  97. 97. XerophthalmiaXerophthalmia is a severe drying of the eye surface caused by a malfunction of the tear glands. it occurs most commonly because of decreased intake orabsorption of vitamin A. Symptoms include night blindness and eye irritation. Dr. Siham Gritly 97
  98. 98. Ulceration and necrosis developed in the cornea that lead to blindness Dr. Siham Gritly 98
  99. 99. 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• Apart from sunlight, dairy products (such as eggs, milk and butter), fatty fish and fish oils are all good sources of vitamin D. Dr. Siham Gritly 99
  100. 100. • Vitamin D comes in many forms, but the two most important in the diet are;-• 1-plant sterol ergosterol which isolated from plant and by commercial irradiation ligh UV coverted to vitamin D2 or ergocalciferol• 2-animal sources or naturally produced called vitamin D3 or cholecalciferol. Dr. Siham Gritly 100
  101. 101. Vitamin D2 and Vitamin D3 a group of steroid compoundVitamin D2 Vitamin D3ergocalciferol cholecalciferol. Dr. Siham Gritly 101
  102. 102. 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 102
  103. 103. 7-Dehydrocholesterol and Ergosterol structures7-Dehydrocholesterol;accumulates in the skin Ergosterol previtaminBy sunlight converted to D2 found in plant foodscholecalciferol not found in human tissues Dr. Siham Gritly 103
  104. 104. Active form of the hormone 1,25-dihydroxycholecalciferol• 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 104
  105. 105. activation of vitamin D must be achievedthrough;• 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 105 kidneys
  106. 106. 25-hydroxyvitamin D3in the liver enzyme 25-hydroxylase hydroxylate cholecaciferol at carbon 25 to form 25-OH cholecalciferol/D3 Dr. Siham Gritly 106
  107. 107. • In the kidneys;-a second hydroxylation of 25-OH D3 (25-hydroxylcalcefirol) occur at position 1• by the action of enzyme 1-hydroxylase in the kidnyes, 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 majour protein in the blood transported the active form calcitriol (1,25-(OH)2 cholecalciferol) to the target tissues Dr. Siham Gritly 107
  108. 108. • 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 108
  109. 109. 1,25-dihydroxyvitamin D3 by the action of enzyme 1-hydroxylase in the kidnyes, 25-cholecalsiferol hydrolyized to 1,25-(OH)2 cholecalecalciferol active form of vitamin D Dr. Siham Gritly 109
  110. 110. • 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 110
  111. 111. 1,25-dihydroxcholecaliciferol D3 formation Tissue cholesterol ↓ Sun ↓ 7-dehydrocholesterol Plasma Cholecaliciferol D3 ↓ liver 25-hydroxycholecaliciferol ↓ kidneys1,25-dihydroxycholecaliciferol → target tissue Dr. Siham Gritly 111
  112. 112. 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 112
  113. 113. • 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. Highlight 12 describes the many factors that lead to osteoporosis, a• condition of reduced bone density. Dr. Siham Gritly 113
  114. 114. Vitamin E tocopherol• 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 114
  115. 115. • 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 115
  116. 116. • 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 116
  117. 117. • In addition to vitamin E, the body has various other antioxidant compounds, such as glutathione peroxidase, catalase, superoxide dismutase, to protect against oxidative damage. Dr. Siham Gritly 117
  118. 118. Alpha-Tocopherol structurealcoholic hydroxyl group and a 12-carbon aliphatic side chain containing two methyl groups in the middle and two more methyl groups at the end the side chain is saturated Dr. Siham Gritly 118
  119. 119. 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 is needed for the process of clotting of blood and Ca2+ binding. Vitamin K can be synthesized by bacteria in the intestines. Vitamin K is needed for catalyzing the carboxylation of the γ-carbon of the glutamate side chain in proteins. Dr. Siham Gritly 119
  120. 120. Vitamin Kphylloquinone and menaquinone share a methylated ring structure Dr. Siham Gritly 120
  121. 121. • 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 121
  122. 122. • 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 122
  123. 123. Dr. Siham Gritly 123
  124. 124. Vitamins that are Cofactor & coenzyme Precursors Chemical AdditionalCofactor Vitamin group(s) Distribution component transferredThiamine 2-carbon Bacteria,pyrophosphate Thiamine (B1) None groups, α archaea and[24] cleavage eukaryotes Bacteria,NAD+ and Niacin (B3) ADP Electrons archaea andNADP+ [25] eukaryotes Bacteria,Pyridoxal Amino and Pyridoxine (B6) None archaea andphosphate [26] carboxyl groups eukaryotes Bacteria, electrons, acylLipoamide [3] Lipoic acid None archaea and groups eukaryotes Bacteria,Methylcobalam Dr. Siham Gritly 124 Vitamin B12 Methyl group acyl groups archaea andin [27]
  125. 125. Bacteria, Cobalamine hydrogen, alkylCobalamine [3] None archaea and (B12) groups eukaryotes Bacteria,Biotin [28] Biotin (H) None CO2 archaea and eukaryotes Acetyl group Bacteria, PantothenicCoenzyme A [29] ADP and other acyl archaea and acid (B5) groups eukaryotes Methyl, formyl, Bacteria,Tetrahydrofolic Glutamate methylene and Folic acid (B9) archaea andacid [30] residues formimino eukaryotes groups Dr. Siham Gritly 125
  126. 126. Bacteria,Menaquinone Carbonyl group[31] Vitamin K None archaea and and electrons eukaryotes Bacteria,Ascorbic acid[32] Vitamin C None Electrons archaea and eukaryotesFlavin Bacteria,mononucleotid Riboflavin (B2) None Electrons archaea ande [33] eukaryotes Bacteria,Flavin adenine Riboflavin (B2) None Electrons archaea anddinucleotide [33] eukaryotesCoenzyme Riboflavin (B2) Amino acids ElectronsF420 [34] Dr. Siham Gritly 126
  127. 127. • 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). Lehningers 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.• http://wiki.answers.com/Q/What_is_dehydration_synthesis#ixzz2BuiK645 Dr. Siham Gritly 127
  128. 128. • 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). Natures 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. http://media.iupac.org/publications/pac/2002/pdf/7405x0787.pdf.• http://www.differencebetween.com/difference-between-acyl-and-vs-acetyl/#ixzz2HmrSvksL Dr. Siham Gritly 128
  129. 129. • acyl group is characterized by a carbon and oxygen atom, which is linked by a double bond. Identifying an acyl group is easy because of the C=O part.• Acetyl group is a common example for an organic acyl group. This is also known as ethanoyl group. It has the chemical formula of CH3CO. Therefore, the R group in the acyl is replaced by a methyl group. Other bond in the carbon can be with a –OH, -NH2, -X,-R,-H etc. For example, CH3COOH is known as acetic acid. The introduction of an acetyl group into a molecule is called acetylation. Dr. Siham Gritly 129