Vitamins 2024 PDF

1  TUMS Shadi Seyyed Ebrahimi PhD; Department of Clinical Biochemistry [email protected] 2 Reference 3  Origin of the word VITAMIN Casimir Funk, a Polish biochemist, isolated an anti- berberi substance from rice polishing....

1  TUMS Shadi Seyyed Ebrahimi PhD; Department of Clinical Biochemistry [email protected] 2 Reference 3  Origin of the word VITAMIN Casimir Funk, a Polish biochemist, isolated an anti- berberi substance from rice polishing.  Named it vitamine  Vital for life  An amine Originally, it was thought these necessary compounds were all amines. Since they were vital to our health they became known as “vital amines”, ie. vitamines. When it was discovered that some were not amines, i.e., not ' --ines', the name was changed to: vitamins 4  What are Vitamins? Vitamins are micronutrients:  Nutritionally important organic compounds  Required in very small amounts.  Cannot be synthesized by the human body.  Do not undergo degradation for providing energy unlike carbohydrates and lipids. Examples: 1. Most mammals can synthesize vitamin C; not humans and primates. 2.  NoPlants mammaland can animals synthesizesynthesize B vitamins butvitamins. rumen bacteria do. 3. Some function as vitamins after undergoing a chemical change: Provitamins (e.g., β-carotene to vitamin A). 5  Coenzymes, Cofactors, and Prosthetic groups Cofactors: Nonprotein components Cofactors may be:  Metal ions  Organic molecules: Vitamins Cofactors bind the enzyme either loosely or tightly  When they bind enzymes tightly, they are considered prosthetic group. 6  Holoenzyme=Active enzyme Holoenzyme (holoprotein) (active) Inactive Apo-enzyme or Nonprotein Apo-enzyme or ? Nonprotein component Apo-protein component Apo-protein Vitamins Loose ionic linkage = Cosubstrate Tight or covalent bound = Prosthetic group 7  Classification Lipid- soluble vitamins are much more soluble in fats, hydrocarbons and similar solvents than in water  Vitamins A, D, K, E Water- soluble vitamins are much more soluble in water than in “organic solvents”.  C, B complex 8 Classification 9  Water-soluble vitamins Vitamins B and C  Easily absorption  Can be in circulation without carriers  Not be stored  Excretion via urine  Not intoxication in the case of over consumption 10  Requirements Water-soluble Name(Letter) RDA (mg) Thiamin (B1) 1.5 Riboflavin (B2) 1.7 Niacin (B3) 2 Pantothenic acid (B5) 10 Pyridoxine (B6) 2 Biotin (B7) 0.3 Folic acid (B9) 0.4 Cobalamin (B12) 6 g Ascorbic acid (C) 60 RDA = Recommended Daily Allowance 11  B Complex - General features 1. Generally act as components of coenzymes in metabolism of carbohydrates, lipids and proteins, especially in energy- yielding reactions.  Dietary requirement is closely linked to metabolic rate. 2. Absorbed by passive diffusion (except B12) in small intestine and any excess is excreted in urine i.e. there is little or no tissue storage (except B12, some folic acid). 3. Must be continually supplied in diet (or by ruminal synthesis). 12  Vitamin B1 - Thiamine  Found in: yeast, Whole grains, legumes, enriched grain products and meat.  Important in: 1. Producing energy from carbohydrates 2. Proper nerve function 3. Stabilizing the appetite 4. Promoting growth and good muscle tone 5. ATP production 13 Metabolic pathways requiring thiamin pyrophosphate  Active form: Thiamin pyrophosphate (TPP)  An essential coenzyme for oxidative decarboxylation: To be assessed by he activation of transketolase in erythrocyte lysate  TTP (thiamine triphosphate) is required for nerve function (unrelated to coenzyme activity). 14  Thiamine Deficiency (B1) Beriberi Beriberi: 1. Dry beriberi: 2. Wet beriberi 2. Peripheral neuropathy, cardiomegaly, tachycardia and decreased muscle strength edema and eventually, muscle paralysis. 15 Alcohol, Wernicke Korsakoff syndrome  In extreme cases, beriberi is associated with Wernicke- Korsakoff syndrome. Wernicke encephalopathy and Korsakoff syndrome are two forms of brain damage caused by thiamine deficiency. Ataxia: inability to coordinate muscular movements due to nervous disorders Confusion Memory loss Opthalmoplegia: can’t follow light source Nystagmus: involuntary jerking of the eye 16  Vitamin B2 or Riboflavin  Needed for good vision and healthy skin  Made of the sugar alcohol ribitol and flavin Isoalloxazine ring 17  Riboflavin Functions  Essential constituent of flavoproteins: – Flavin mononucleotide (FMN) – Flavin adenine dinucleotide (FAD) FMN FAD riboflavin 5’-phosphate FAD Flavokinase FMN + ATP FAD + ppi synthetase (riboflavin kinase) 18  Riboflavin Functions  Hydrogen carrier in:  Glycolysis  TCA cycle  Fatty acid oxidation  Amino acid oxidation  Mitochondrial respiratory chain and oxidative phosphorylation 19  Deficiency symptoms Cheilosis/Angular stomatitis (fissure at the angle of the mouth) Glossitis: Purple smooth tongue due to loss of tongue papillae Localized seborrheic dermatitis of the face Vascular changes in the cornea Anemia  Riboflavin nutritional status is assessed by measurement of the activation of erythrocyte glutathione reductase by FAD added in vitro. 20  Niacin = Vitamin B3 Is it strictly a vitamin ?  To be synthesized in the body from the essential amino acid tryptophan. Nicotinic acid and nicotinamide , have the biological activity of niacin  As the nicotinamide ring of the coenzymes NAD and NADP NAD is the source of : Nicotinic acid Nicotinamide  ADP-ribose for the ADP-ribosylation of proteins  PolyADP-ribosylation of nucleoproteins involved in the DNA repair mechanism 21  Niacin Functions  Active coenzymes:  Nicotinamide-adenine dinucleotide (NAD+)  Nicotinamide-adenine dinucleotide phosphate (NADP+)  Important in hydrogen transfer reactions catalyzed by dehydrogenase enzymes.  ATP synthesis, from oxidation of primary fuels (glucose, fatty acids and to a lesser extent, amino acids) (NAD+).  Also important in reductive biosynthesis (NADP+). NAD+ NADP+ 22  Niacin Deficiency Deficiency symptoms  Pellagra occurs in people who subsist mainly on corn which is low in both niacin and tryptophan  The signs of pellagra include (the three Ds):  Dermatitis  Diarrhea  Dementia  Nutritional etiology of pellagra: Deficiency of tryptophan, niacin, riboflavin or vitamin B6  Genetic disease:  Hartnup  A condition caused by the body's inability to absorb certain amino acids from the diet.  Being used to treat hyperlipidemia.  Intakes of both nicotinic acid and nicotinamide in excess cause liver damage. 24  Vitamin B5 Vitamin B5 (pantothenic / pantothenic acid acid) As a part of coenzyme A and acyl carrier proteins (ACP)  A central role in acyl group metabolism coenzyme A (CoA) in reactions of:  Citric acid cycle  Fatty acid oxidation  Oxidative decarboxylation of pyruvate  Synthesis of cholesterol, bile salts, ketones and steroid hormones.  Prosthetic group for acyl carrier protein (ACP) in fatty acid synthesis  The vitamin is widely distributed and deficiency has rarely been reported in humans. 25  Coenzyme A Peptide------ (ADP) Acyl carrier protein 26  Vitamin B6 Food sources: Bananas, beans, lentils, walnuts, salmon, chicken, beef, whole grain breads and cereals, soybeans, liver, eggs, dairy products are excellent sources. 27  Vitamin B6 Functions FUNCTIONS: B6 is involved in: Amino acid metabolism Transamination reactions required for the synthesis and catabolism of the amino acids. Decarboxylation reactions. Breakdown of glycogen Glycogenolysis (cofactor for glycogen phosphorylase). 80-90% of body vit B6 is present in the muscles, most of it in PLP (coenzyme) form bound to glycogen phosphorylase. Only 1 mol or less is present in the blood, Synthesis of epinephrine (adrenaline) and norepinephrine (noradrenaline) Synthesis of niacin (vitamin B3) from the amino acid tryptophan. 28  Vitamin B6 deficiency  Deficiencies: are rare and usually are related to an overall deficiency of all the B- complex vitamins.  To cause abnormalities of tryptophan and methionine metabolism.  To cause increased sensitivity to steroid hormone action  Development of hormone-dependent cancer of the breast, uterus, and prostate  Anemia  Penicillamine and Isoniazid form complexes with PL and PLP  To cause sensory neuropathy in excessive amount (100-200 mg/day)  Vitamin B6 status is measured by :  Activation of erythrocyte transaminases by pyridoxal phosphate added in vitro  Plasma concentrations of the vitamin  Vitamin B6 is effective in premenstrual syndrome (PMS) and diabetes. 29  Biotin  Sources: liver, soybeans, egg yolk, cereals, legumes, nuts; found combined to lysine (biocytin) or other proteins  Intestinal bacteria can synthesize biotin 30  Biotin functions (acetyl CoA  Biotin functions to transfer CO2 in a carboxylase) - initial step in de small number of reactions novo fatty acid synthesis. pyruvate carboxylase propionyl CoA carboxylase 31  Biotin Deficiency  Deficiency is unknown, except:  people on total parenteral nutrition  People who eat uncooked egg white  Lethargy, depression, hallucinations, anorexia, nausea, loss of hair, dermatitis  This baby developed severe biotin deficiency during intravenous feeding without biotin. 32  Folic Acid (folacin)  Folic acid is obtained primarily from yeasts and leafy vegetables as well as animal liver. Raw foods have more than cooked. Glu Glu Glu Glu Glu 31  Folate The active form of folic acid is tetrahydrofolate (THF) 34  Folate metabolism Methotrexate Trimethoprim pyrimethamine Dihydrofolate Homocysteine reductase DHF THF Methionine dTMP Serine synthase Thymidylate Methionine dUMP Glycine synthase Methylene Methyl THF THF Serine glycine DHF: dihydrofolate hydroxymethyl transferase THF:tetrahydrofolate 33  Deficiency symptoms  Deficiency can occur when there is: 1. Poor dietary habits as those of chronic alcoholics. 2. Anticonvulsants and oral contraceptives can impair the absorption of folate. 3. Pregnancy  Effect of folate deficiency:  Impairment in TMP and purine synthesis  Cell cycle arrest in S-phase of rapidly proliferating cells, especially hematopoietic cells.  The result is megaloblastic anemia as for vitamin B12 deficiency.  Deficiency during pregnancy can cause neural tube defects (NTD) such as spina bifidia.  Cardiovascular disease ( elevated blood homocysteine) 36  Vitamin B12  Vitamin B12 (cobalamin) is cobalt-containing compound possessing the corrin ring (corrinoids) R could be :  Cyanide (CN) in cyanocobalamin.  hydroxyl group (-OH) in hydroxycobalamin In the coenzyme forms of vitamin B12: – R equals an adenosyl group in adenosylcobalamin. – R equals a methyl (-CH3) group in methylcobalamin.  Vitamin B12 is synthesized by microorganisms (bacteria) and found in muscle meats, fish, shellfish, dairy products and eggs, there being no plant sources of this vitamin. 37  Metabolic pathways requiring cobalamin catabolism of fatty acids with an odd number of carbon In the cytosol atoms and the amino acids valine, In isoleucine mitochondria and threonine cholestrol 38  Vitamin B12 absorption (cobalophilin)  It is transported to the liver and other tissues in the blood bound to transcobalamin II.  It is stored in the liver attached to transcobalamin I. 39  Vitamin B12 deficiency  Pernicious anemia  Failure of the absorption of vitamin B12 rather than dietary deficiency  Failure of intrinsic factor secretion caused by autoimmune disease affecting parietal cells  production of anti-intrinsic factor antibodies.  Vitamin B12 deficiency impairs the metabolism of folic acid  To cause release of immature precursors of erythrocytes into the circulation (megaloblastic anemia).  Neurological disorders  Due to progressive demyelination of nerve cells results from increase in methylmalonyl-CoA. 40  Vitamin C (Ascorbic acid)  It is derived from glucose via uronic acid pathway.  L-gluconolactone oxidase is responsible for conversion of gluconolactone to ascorbic acid.  Both ascorbic acid and dehydroascorbic acid have vitamin activity. 41  Vitamin C (ascorbic acid) Anti-oxidant agent Collagen synthesis, proline hydroxylase and lysine hydroxylase Copper-containing hydroxylases (Dopamine β-hydroxylase) Enhancing iron (Fe2+) absorption in the gut Synthesis of carnitine 42  Vitamin C (ascorbic acid) Proline hydroxylase in formation of osteocalcin Blood-clotting cascade Scar tissue repair Common cold?? 43 Vitamin C Deficiency Causes Scurvy  Fragility of blood capillaries  Bleeding gums, tooth loss  Small red spots on skin  Rough skin  Wounds fail to heal  Weak bones  Anemia and infections 44 45 46  Fat soluble vitamins  Including: vitamins A, D, E and K  Digestion and absorption dependent on digestion and absorption of lipids  Vitamins A and D have specific carriers, others carry by lipoproteins  Storing in adipose and liver tissues  Excretion via bile  Intoxication in the case of over consumption 47  Requirements Name (Letter) RDA Retinol (A) 5000 IU Calciferol (D) 400 IU Tocopherol (E) 30 IU Phylloquinone (K) 70 g 48 49  Vitamin A Retinoids contain -ionone ring and an isoprenoid side chain with either a: Hydroxyl group: Retinol Aldehyde group: Retinaldehyde Carboxylic acid group: Retinoic acid All-trans-retinal 11-cis-retinal Retinol Retinoic Acid Can’t be reduced to retinol or retinal in the body. 50  Provitamin A  Provitamin A: α-, β-, and γ-carotenes Beta-carotene is the most abundant and widespread provitamin A.  Dark-green leafy vegetables (spinach) and yellow-orange fruits (apricots and mango) and vegetables (carrots, yellow squash and sweet potatoes) are high in beta-carotene.  Carotenoids are not toxic even at high doses for long times. 51 Vitamin A Uptake, Absorption, Transport & Storage Intestine Lumen Diet Vegetables Enterocytes β-carotene Bile acid dioxygenase Β-Carotene Retinyl Β-Carotene All trans retinal Esters LPL Retinal Pancreatic Reductase hydrolase Bile acid Retinol Retinol Retinoic Acid Retinyl Esters RBP:Retinol-binding protein TTR:Transthyretin 50  Role of Vitamin A in Vision  Vitamin A (retinal) is an essential precursor for formation of the visual pigment, rhodopsin, in the retina of the eye.  Retinal plays an important role in vision, especially night vision. Visual Pigment 53  Vitamin A in growth and differentiation  All-trans-retinoic acid and 9-cis-retinoic acid regulate:  Growth  Development  Tissue differentiation  Retinoic acid binds to nuclear receptors that bind to response elements of DNA and regulate the transcription of specific gene RAR: retinoic acid receptor 54 RARE: retinoic acid receptor elements  Vitamin A: Biological functions  Bone and teeth formation  Maintenance of healthy hair, skin and mucous membranes.  Reproduction  Boosts the body's immune system  Antioxidant 55  Vitamin A Deficiency  The most important preventable cause of blindness.  The earliest sign impairment to adapt to dim light, then night blindness, an inability to see in the dark.  More prolonged deficiency leads to xerophthalmia: keratinization of the cornea, and blindness.  Vitamin A also has an important role in differentiation of immune system cells, and even mild deficiency leads to increased susceptibility. to infectious diseases.  Anemia 56  Vitamin A: Toxicity  Has occurred through eating polar bear liver.  There is only a limited capacity to metabolize vitamin A, and excessive intakes lead to accumulation beyond the capacity of intracellular binding proteins;  Unbound vitamin A causes membrane lysis and tissue damage  Symptoms of toxicity:  Central nervous system (headache, nausea, ataxia, and anorexia)  Liver (hepatomegaly with histological changes and hyperlipidemia)  Calcium homeostasis (thickening of the long bones, hypercalcemia, and calcification of soft tissues)  Skin (excessive dryness and alopecia). 57  Vitamin D  Vitamin D is not strictly a vitamin since it can be synthesized in the skin, and under most conditions this is the major source of the vitamin  For humans, the two most important forms of vitamin D are:  Vitamin D2 (ergocalciferol)  Vitamin D3 (cholecalciferol).  Its main function is in the regulation of calcium absorption and homeostasis  Most of its actions are mediated by way of nuclear receptors that regulate gene expression 58 Vitamin D Synthesis in the Skin 59 Vitamin D synthesis and activation Calcitriol is also called 1,25-dihydroxy vitamin D3, or 1,25-(OH)2D3. Liver Kidney Kidney Kidney Kidney 60  Vitamin D functions  Calcitriol functions in concert with parathyroid hormone (PTH) and calcitonin to regulate serum calcium and phosphorous levels  Vitamin D is essential for normal insulin secretion by the pancreas. 61  Vitamin D deficiency  Rickets in children:  The bones are undermineralized as a result of poor absorption of calcium.  Osteomalacia in adults results from the demineralization of bone, especially in women who have little exposure to sunlight, especially after several pregnancies.  Although vitamin D is essential for prevention and treatment of osteomalacia in the elderly, there is less evidence that it is beneficial in treating osteoporosis. 62  Higher intake of vitamin D To be protective against :  Prostate and colorectal cancer  Prediabetes  Metabolic syndrome. Hints:  While increased sunlight exposure would meet the need, it carries the risk of developing skin cancer.  Too much (5 times the RDA): It is most toxic of the vitamins. o Nausea o Loss of appetite o Hypercalcemia  Calcium gets deposited in soft tissues, arteries and kidneys. 63  Vitamin E  Vitamin E is the generic descriptor for two families of compounds:  Tocopherols  Tocotrienols Chromanol ring 64  Vitamin E  To act as a lipid-soluble antioxidant in cell membranes. Stable Molecule Antioxidant Free Radical Unstable molecule Unpaired electron  D-α-tocopherol protects the fat component in low-density lipoproteins (LDLs) from oxidation and has shown moderate cholesterol-lowering capabilities.  To be important in maintaining the fluidity of cell membranes.  D-α-tocopherol has been shown to inhibit the "clumping" of blood platelets (thus helping to avoid blood clots) 65  Vitamin E deficiency o Dietary deficiency of vitamin E in human beings is unknown. o The major site of vitamin E storage is in adipose tissue. o Patients with severe fat malabsorption, cystic fibrosis, and some forms of chronic liver disease suffer deficiency, exhibiting nerve and muscle membrane damage.  Premature infants are born with inadequate reserves of the vitamin.  The erythrocyte membranes are abnormally fragile as a result of lipid peroxidation, leading to hemolytic anemia. 66  Vitamin K  The "K" in vitamin K comes from the German word "koagulation," which refers to blood clotting (coagulation).  Three compounds have the biological activity of vitamin K:  Vitamin K1: Phylloquinone; the normal dietary source, found in green vegetables  Vitamin K2 : Menaquinones; synthesized by intestinal bacteria, with differing lengths of side chain  The most biologically active form of vitamin K, is found in egg yolks, butter, liver, cheddar cheese and yogurt  Vitamin K3 : Menadione; synthetic water soluble compounds  Antagonists of vitamin K are used to reduce blood coagulation in patients at risk of thrombosis; the most widely used is warfarin. Menadione 67  -Carboxylation  Carboxylation of specific glutamate residues in calcium binding proteins.  Prothrombin and several other proteins of the blood clotting system.  Osteocalcin and the matrix Gla protein in bone  Nephrocalcin in kidney 68  Vitamin K Deficiency Prolonged use of antibiotics Malabsorption and biliary tract obstruction  Elevated prothrombin time (PT) and bleeding time (BT) In immediate post-natal infants – Low fat store – Sterility of the infantile intestinal tract – Low breast milk levels of Vit K – Poor placental transport 69 Fat Soluble Vitamins vs. Water Soluble Vitamins 71