Lecture_Vitamins-2020.pdf
- 2. ❖ Organic molecules, essential for the normal growth and development, required in tiny amounts Introduction to Vitamins VITAL + AMINES = VITAMIN ❖ Cannot be synthesized in sufficient quantities by mammalian cells; must be supplied in the diet Vitamin C – vitamin for human Vitamin K, H – synthesized by gut flora Vitamin A - from precursor beta carotene
- 3. FUNCTIONS • Regulate metabolism, help convert lipids and saccharides into energy (B-complex) • Hormones (vitamin D) • Antioxidants (vitamin E, C) • Regulators of cell and tissue growth and differentiation (vitamin A) • Coenzyme precursors (B-complex)
- 4. AVITAMINOSIS - chronic or long-term vitamin lack (beri-beri, scurvy, rickets and pellagra) HYPOVITAMINOSIS - any of several diseases caused by deficiency of one or more vitamins HYPERVITAMINOSIS – the condition resulting from the chronic excessive intake of vitamins (vitamin supplements) side effects – nausea, diarrhea, vomiting
- 5. Avitaminoses ▪ Vitamin A deficiency causes xerophthalmia or night blindness ▪ Thiamine (B1) deficiency causes beri-beri ▪ Niacin (B3) deficiency causes pellagra ▪ Vitamin B12 deficiency leads to megaloblastic anemia ▪ Vitamin C deficiency leads to scurvy ▪ Vitamin D deficiency causes rickets ▪ Vitamin K deficiency causes impaired coagulation ▪ Rare in developed world - fortification
- 6. ANTIVITAMINS H2N C O OH Paraaminobenzoic acid (PABA) H2N S O NH2 O Sulphonamide Sulphonamides – prevent bacterial multiplication, without toxicity to the human tissues • substances that destroy or inhibit the metabolic action of a vitamin Classification: 1. Enzymes decomposing vitamins (thiaminase, ascorbase) 2. Compounds forming nonactive complexes with vitamins (avidin) 3. Compounds structurally similar to vitamins (sulphonamides)
- 7. Water Soluble Vitamins Fat Soluble Vitamins Thiamine (B1) Riboflavin (B2) Niacin (B3) Panthotenic acid (B5) Pyridoxin (B6) Biotin (B7 ) – vitamin H Folic acid (B9) Cobalamin (B12) Bioflavonoids (P) Ascorbic acid (vit. C) Vitamin A - Retinol Vitamin D - Calciferol Vitamin E - Tocoferol Vitamin K – Quinons Vitamin F Water soluble vitamins Fat soluble vitamins
- 8. Vitamins soluble in water ➢ directly absorbed from intestine into blood ➢ hypervitaminosis – vitamins excreted from the body Vitamins soluble in fat ➢ require correct function of the liver and gall bladder ➢ hypervitaminosis – toxic effect
- 9. Its provitamin - -carotene - (red, orange pigments in plants and fruits) - Antioxidant -CAROTENE VITAMIN A (R E T I N O L) Structure: tetraterpenoid containing -ionone ring with an unsaturated side chain -, - a - provitamin A
- 10. α - Carotene β - Carotene γ - Carotene
- 11. dioxygenáza CHO COOH all-trans retinal izomeráza kyselina retinová dehydrogenáza CH2OH trans retinol1 - vitamín A1 Premeny β-karoténu a vitamínu A1 15' 1 11 11 1 1 CHO Fe2+ O2 11-cis retinal β-karotén 15 -carotene dioxygenase Retinoic acid isomerase dehydrogenase 2
- 12. All-trans-retinal 11-cis-retinal Retinol Kyselina retinová Retinoic acid
- 13. Functions of vitamin A ❖ Vision – retinal is a structural part of rhodopsin (visual purple) – light sensitive pigment in retina ❖ Bone remodeling – function of osteoblasts and osteoclasts depend on it. ❖ Reproduction – sperm production, menstrual period ❖ Resistance to infectious disease – deficiency leads to increased frequency and severity of disease
- 14. RHODOPSIN (PIGMENT) LIGHT cis-RETINAL trans-RETINAL-OPSIN NERVE IMPULS TRANS-RETINAL NADH+H+ DEHYDROGENASE NAD+ TRANS -RETINOL OPSIN RETINAL ISOMERASE R E T I N A Retinolesters (liver) transport by blood proteins VISION CYCLE
- 15. HYPOVITAMINOSIS A ➢ Night blindness – mild deficiency of vitamin A – inability to produce sufficient amount of rhodopsin (lack of retinal) ➢ Large deficiency of vit. A – xeroftalmia – keratinisation of the eye tissue (today in Africa, Asia) ➢ Dry skin, frequent infections, decreased synthesis of thyroid hormones
- 16. HYPERVITAMINOSIS β-carotene supplements (high doses) • Skin discoloration • Lung cancer / smokers / Retinal • Birth defects • Liver problems • Reduced bone mineral density that may result in osteoporosis • Hair loss • Excessive skin dryness/peeling • Death Signs of acute toxicity – nausea, vomiting, headache, dizziness, blurred vision, loss of muscular coordination
- 17. SOURCES The body stores both retinol and beta-carotene in the liver, drawing on this store whenever more vitamin A is needed β-carotene - carrot, green leafy vegetables – spinach, kale, sweet potatoes, yellow and orange fruits Retinal – liver of polar bear, seal, eggs and fatty fish
- 18. VITAMINS D - CALCIFEROL • maintain normal blood levels of Ca and P by promoting their absorption from food in the intestines and reabsorption of Ca in the kidneys, enabling normal mineralization of bones 2 major forms: D2 – derived from precursor ergosterol present in plants D3 – derived from precursor 7-dehydrocholesterol present in skin Structure of provitamins of vitamin D - similar to steroid hormones - derived from cholesterol
- 19. UV 7-dehydrocholesterol (skin) cholecalciferol (provitamin) (D3, calciol) UV Ergosterol (plants) ergocalciferol (D2, ercalciol) (provitamin) Adequate amounts of vitamin D3 can be made in the skin after only 10 -15 minutes of sun exposure at least 2x per week to the face, arms, hands, or back without a sunscreen
- 22. Normal vitamin D metabolism
- 23. DEFICIENCY ◼ Results from a number of factors: ◼ inadequate intake coupled with inadequate sunlight exposure ◼ liver or kidney disorders (impair conversion of vitamin D into active metabolites)
- 24. DEFICIENCY Leads to impaired bone mineralization, and to bone softening diseases including: • RICKETS - a childhood disease - impeded growth, and deformity of the long bones • OSTEOPOROSIS - reduced bone mineral density and increased bone fragility
- 25. Odd curve to spine or back Wide joints at elbow and wrist Odd-shaped legs
- 27. Vitamin D malnutrition may also be linked to an increased susceptibility to several chronic diseases: ◼ high blood pressure ◼ cancer ◼ periodontal disease ◼ multiple sclerosis ◼ memory loss ◼ autoimmune diseases including type 1 diabetes
- 28. Overdose of vitamin D: ◼ Ca release from bones and its deposition in soft tissues (kidneys, lungs gall bladder, endocrine glands) causing their calcification
- 29. Sources of vitamin D ◼ Fish liver oils ◼ Fatty fish species ◼ A whole egg ◼ Beef liver, cooked ◼ mushrooms (Vitamin D2)
- 30. • Benefits • Protects lipids (cell membranes), DNA, proteins from oxidation – ANTIOXIDANT Protects food fats from going rancid • Helps to form red blood cells • Aids in the absorption of vitamin K Vitamin E – Tocopherols antisterile vitamin
- 31. Free radical Cell Mitochondria Vitamin E protects cell membrane lipids from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction
- 32. O CH3 CH3 CH3 CH3 R3 R2 HO R1 O HO CH3 CH3 CH3 CH3 CH3 R1 R2 R3 Tocol -CH3 -CH3 -CH3 -CH3 -H -CH3 -H -CH3 -CH3 -H -H -CH3 tocotrienol STRUCTURE: tocol, forms 8 basic derivatives α-tocopherol is the most effective form Chromanol ring HO- group - reduction of free radicals Saturated side chain – penetration in membranes R1 R2 R3
- 33. Deficiency neurological problems, anemia Natural Sources green leafy vegetable, vegetable oils, nuts, seeds, spinach, broccoli, soybean oil
- 34. Vitamin K1 (phylloquinone) - from plant sources Vitamin K2 (menaquinone) - made by intestinal bacteria (production can be disturbed by antibiotics, Crohn disease) Vitamin K3 (menadione, menadiol) - synthetic form German „koagulation“ vitamin K VITAMIN K - QUINONES
- 36. • Promotes normal blood clotting (coagulation) • Bone metabolism • Vascular health Biochemistry coenzyme of an enzyme carboxylase – carboxylation of glutamic acid gamma- carboxyglutamic acid (Gla) – involved in binding Ca2+ FUNCTIONS
- 37. nonactive active clotting factor-glutamic acid clot.factor-Gla-Ca2+ CO2 Vitamin K Carboxylase
- 38. The vitamin K cycle
- 39. Rare in healthy adults: 1) vitamin K widespread in foods 2) vitamin K cycle conserves vitamin K 3) large intestine bacteria synthesize vit. K Deficiency Adults at risk: • those taking vitamin K antagonist - anticoagulant drugs • adults with significant liver damage • newborn babies – exclusively breast-fed: 1) vitamin K is not easily transported across the placental barrier 2) the newborn's intestines are not yet colonized with bacteria that synthesize menaquinones 3) the vitamin K cycle may not be fully functional in newborns
- 40. Natural Sources green leafy vegetables – alpha-alpha, Brussel sprouts, spinach, kale, cabbage, avocado, cheddar cheese
- 42. VITAMIN B1 – THIAMINE, ANEURINE (antineuritic factor, antiberiberi factor) PYRIMIDINE and THIAZOL rings linked through the methylene bridge Antagonists – Sulfites (food preservatives) – attack at the methylene bridge
- 43. - cofactor for several enzymes (pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase) Thiamine diphosphate COENZYME = thiamine diphosphate - in the catabolism of saccharides and aminoacids
- 44. Deficiency ▪ severely reduced capacity of cells to generate energy ▪ BERI-BERI - neurological symptoms, cardiovascular abnormalities, and edema with fatal outcome It affects the nerves to the limbs, producing pain, paralysis, and swelling Natural Sources Meat, potatoes, bananas, lentils, beans, yeast Overdose Hypersensitive reactions resembling anaphylactic shock Interactions Antibiotics - decrease thiamine level
- 45. Beri – beri disease
- 46. VITAMIN B2 – RIBOFLAVIN METHYL DERIVATE OF ISOALOXAZINE + RIBITOL Lactoflavin, ovoflavin, vitamin G Riboflavin powder. Riboflavin solution ribitol
- 48. H - H+ FAD Nitrogens 1 & 5 bind hydrogens in FADH2
- 49. Deficiency Fatigue, red, swollen, cracked mouth and tongue, mouth ulcers, cracks at the corners of the mouth Riboflavin deficiency is often seen in chronic alcoholics due to their poor dietetic habits Overdose Itching, numbness, a burning sensation Storage Riboflavin decomposes when exposed to visible light This characteristic can lead to riboflavin deficiencies in newborns treated for hyperbilirubinemia by phototherapy
- 50. Vitamin B3, Niacin, vitamin PP Nicotinamide Nicotinic Acid Niacin is not a true vitamin in the strictest definition since it can be derived from tryptophan. nicotinic acid + vitamin !
- 51. Nicotinamide adenine dinucleotide (NAD+) and Nicotinamide adenine dinucleotide phosphate (NADP+) - cofactors for numerous dehydrogenases (lactate, malate dehydrogenases) - acceptor of during alcohol oxidation NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD+) H- NADH -OH phosphorylated in NADPate !
- 52. Reduction of NAD+ to NADH
- 53. Function • Niacin is a precursor to NADH, NAD+ - coenzymes of oxido-reductases – transfer of hydrogen anion • Nicotinic acid (but not nicotinamide) - lowers plasma cholesterol levels (and TAG, LDL, VLDL) and has been shown to be a useful therapeutic for hypercholesterolemia • Elevates blood glucose and uric acid production (not recommended for diabetics or gout)
- 54. Deficiency Dermatitis on the hands and face, weakness The severe symptoms, depression, dermatitis and diarrhea - PELLAGRA (3D disease) Natural Sources Beef liver, brewer’s yeast, meat, eggs, grains and milk
- 55. PELLAGRA
- 56. Overdose Niacin flush, liver damage, stomach ulcers, nausea, diarrhea, weakness
- 57. Overview • Pantothenate is required for synthesis of coenzyme A – metabolism of saccharides, proteins, lipids. • Growth factor for MO • „Anti-stress vitamin“ Vitamin B5 – Pantothenic Acid
- 59. SOURCES Whole grains - milling removes much of the pantothenic acid Vegetables – broccoli, avocados Meats, rice, alfalfa, peanuts, molasses, yeasts DEFICIENCY Excessive fatigue, sleep disturbances Deficiency - extremely rare due to its widespread distribution in whole grain cereals, meat
- 60. Pyridoxine (Pyridoxol ) Pyridoxal Pyridoxamine Pyridoxal Phosphate (PDP) All three compounds are efficiently converted to the biologically active form of vitamin B6, PYRIDOXAL PHOSPHATE (PDP) Vitamin B6 – Pyridoxine ! !
- 61. FUNCTIONS ➢ Affects the body’s use of proteins, saccharides • a coenzyme in all transamination reactions, in some decarboxylation and deamination of amino acids ➢ PDP aids in the synthesis of heme ➢ Helps in absorption of vitamin B12 and formation of erythrocytes ➢ Role in the conversion of tryptophan to serotonin – helps against mental depression
- 62. ➢ Vitamin B6-magnesium - help attention deficit disorder - improvements in hyperactivity, and improved school attention ➢ Vitamin B6 - cure for premenstrual syndrome (PMS) Deficiency • Anemia • Nerve damage (mental confusion, irritability, nervousness) • Skin problems • Sores in the mouth Deficiencies of vitamin B6 are rare
- 63. Natural Sources Potatoes, Salmon, Shrimp, grains, soya, yeasts, poultry, fish, eggs, nuts Interactions Tobacco/alcohol - Reduces vitamin absorption rates
- 64. FUNCTION • Cofactor of enzymes that are involved in CARBOXYLATION reactions (e.g. acetylCoA carboxylase, pyruvate carboxylase) helps to transfer CO2 • Key role in the metabolism of lipids, proteins and saccharides • It activates protein/amino acid metabolism in the hair roots and fingernail cells - the “beauty vitamin” - often recommended for strengthening hair and nails. • Role in DNA replication and transcription VITAMIN H - BIOTIN
- 65. Carboxybiocytin Biotin Biocytin imidazol valeric acid tiophane STRUCTURE - imidazol and thiophane heterocyclic ring with valeric acid
- 66. DEFICIENCY • hair loss, hair thinning • brittle fingernails • depression, halucination, • muscle pain, • dermatitis (skin rash, typically on the face) Synthetized by intestinal bacteria - deficiencies rare
- 67. Deficiency occurs in: • Alcoholics • People with inflammatory bowel disease • Someone who eats large quantities of raw egg whites • Long-term antibiotic use Raw eggs - preventing absorption of biotin vit. H deficiency avidin from egg whites + biotin = complex SOURCES gut flora, liver, egg yolk, nuts, seeds, soya
- 68. : Functions • Nucleotide biosynthesis • DNA and RNA synthesis and repair • Important during periods of rapid cell division and growth • Production of red blood cells, prevention of anemia. • Antioxidant Vitamin B9 - Folic Acid Folacin Benefits • To carry and transfer various forms of one carbon units (methyl, methylene, methenyl, formyl or formimino groups) during biosynthetic reactions (purine nucleotides, dTMP) • Promotes a healthy pregnancy
- 69. Folic Acid positions 7 & 8 carry hydrogens in dihydrofolate (DHF) positions 5-8 carry hydrogens in tetrahydrofolate (THF) • Active form of folic acid - tetrahydrofolate (THF) – coenzyme F – formylating coenzyme – transfer of 1-carbon moeities pterin PABA Glutamic acid • Folic acid is itself not biologically active, but derivative tetrahydrofolate and other derivatives after folic acid conversion to dihydrofolic acid in the liver
- 70. Deficiency ◼ Neural tube defects in developing embryos ◼ Megaloblastic anaemia, ◼ mood disorders and gastrointestina ldisorders Overdose dizziness, headache, anxiety, nausea,vomiting Natural Sources animal liver and kidneys, sardines, beef, tuna, trout, salmon
- 71. Spina bifida • Malformation of the spine • Lost ability to control bladder - urination, • Impaired function of legs
- 72. Function • Synthesis of DNA and erythrocytes • Coenzyme during conversion of methylmalonyl CoA to succinyl CoA • Functioning of brain and nervous system • Antioxidant • B12 is used to regenerate folate in the body VITAMIN B12 - Cobalamin Natural Sources Animal liver and kidneys, sardines, beef, tuna, salmon, dairy products, eggs
- 74. B12 - protein B12 protein Intrinsic faktor (IF) (stomach) B12-IF Absorption (small intestine) B12-transcobalamine II (circulation) Transcobalamine II B12 Synthesis (MO) Hydrolysis (stomach)
- 75. Binding of B12-transcobalamin II to the cell receptors Endocytosis of the complex into cells Degradation of the complex in lysosomes and liberation of B12 Coenzyme of enzymes in the cell cytoplasm
- 76. Mouth Salivary glands produce R-protein Stomach a. HCl and pepsin release vitamin B-12 bound to protein in food b. Free vitamin B-12 binds with R-protein c. Parietal cells secrete IF (intrinsic factor) Small intestine a. Trypsin from pancreas releases R-protein from vitamin B-12 b. Vitamin B-12 links with IF intrinsic factor Ileum Vitamin B-12/ Intrinsic factor complex is absorbed into blood and binds to transport protein transcobalamin II Liver Vitamin B-12 stored in liver VITAMIN B-12 absorption Small intestine Ileum Stomach Liver Salivary gland
- 77. Deficiency – develops if the body does not produce enough intrinsic factor, or if you don’t eat enough vitamin-B12-rich foods Pernicious anaemia Nausea, loss of appetite, sore mouth Deficiencies - rare The liver can store up to six years worth of vitamin B12 Interactions Tobacco/Alcohol - Reduces the absorption of vitamin B12
- 78. Blood cells of pernicious anemia The cells are larger than normal and irregular in shape Normal blood cells The size, shape and color of these red blood cells show that they are normal.
- 79. Overview Participates in oxidation-reduction reactions Ascorbic acid Dehydroascorbic acid !
- 80. Gulonic acid L-ascorbic acid L-dehydroascorbic acid Enzyme block ➢ The vast majority of vertebrates are able to synthesize their own ascorbic a excluding humans, guinea pigs, bats) from glucose.
- 81. ✓ Antioxidant (prooxidant) ✓ Cofactor of enzymes used in the synthesis of collagen ✓Tyrosine degradation ✓ Adrenalin synthesis ✓ Carnitin synthesis ✓ Bile acids production ✓ Steroidogenesis ✓ Iron absorption ✓ Metabolism of bone minerals FUNCTION
- 82. SCURVY Fragility of capillaries Gums bleeding Swallen gums
- 83. Overdose Flushed face, headache, increased urination, lower abdominal cramps Natural Sources Fruits and vegetables
- 84. • Pigments for flower coloration producing yellow or red/blue pigmentation • They also protect plants from attacks by microbes and insects VITAMIN P – BIOFLAVONOIDS
- 85. ❖ • Found in close association with vitamin C - vitamin C . ❖ • Bioflavonoids help maximize the benefits of vitamin C by inhibiting its breakdown in the body ❖ • Antioxidants, antivirals, and anti-inflammatories ❖ • Protection against infections ❖ • Decrease the cholesterol level Flavonoids
- 86. • Strengthening the walls of the blood vessels (rutin) ❖ • Preventing nosebleeds, miscarriages, postpartum bleeding, and other types of hemorrhages ❖ • Protection against cancer and heart disease ❖ • Anticoagulant activity (preventing blood clotting) ❖ • Improvement of circulation ❖ • Improvement of liver function ❖ • Improvement of vision and eye diseases Essencial compounds are rutin, hesperidin, quercetin.
- 87. Sources Citrus fruits, grapes, black current, blackberries, blueberries, cherries, apricots, cacao, tea Absorption of the bioflavonoids can be slow, but small amounts can be stored in the body
- 88. LIPOIC ACID Coenzyme – aerobic decarboxylation and transacylation during photosynthesis Growth factor of several bacteria and protozoa Antioxidant - acts in hydrophilic and lipophilic environment - dihydrolipoic acid regenerates glutathione, vitamin C and E LIPOIC ACID
- 90. Chelator • Lipoic acid – chelates Cu2+, Zn2+ and Pb2+, but not Fe3+. • Dihydrolipoic acid – chelates Cu2+, Zn2+ a Pb2+ and Fe3+. - prooxidant – it can reduce Fe3+ to Fe 2+ • Lipoic acid intravenous administration - mushroom poisoning, heavy metal intoxication Sources - kidney, heart, liver, spinach, broccoli, peas, potatoes Brewer´s yeasts
- 91. UBIQUINONE – COENZYME Q • Present in the respiratory chain of mitochondria • Transports electrones • Important for energy production in cells • Antioxidant • It is not a vitamin - all animals, including humans, can synthesize ubiquinones • Fat soluble
- 92. Coenzyme Q3 CH3 CH2=C - CH=CH2 isoprene (2-methyl-1,3-butadiene )
- 94. • Deficiency Decreased plasma levels of coenzyme Q10 - diabetes, cancer, and congestive heart failure • Sources meat, poultry, fish, nuts, moderate sources - fruits, vegetables, eggs, and dairy products
- 95. ADENOSINEPHOSPHATES Adenine Ribose Triphosphoric acid - donors and acceptors of phosphoric acid in all living systems 5´
- 97. Adenosine-5'-triphosphate (ATP) • Transports chemical energy within cells for metabolism • It is an energy source produced during photosynthesis and cellular respiration • It is consumed by many enzymes in biosynthetic reactions, motility, and cell division.
- 98. • ATP - substrate in signal transduction pathways by KINASES - phosphorylate proteins ADENYLATE CYCLASE - uses ATP to produce the second messenger cyclic AMP • ATP is also incorporated into nucleic acids • ATP has several negatively charged groups in neutral solution, it can chelate metals with very high affinity • Due to the strength of these interactions, ATP exists in the cell mostly in a complex with Mg2+ cAMP