Vitamins - Near East University

Vitamins Prof. Dr. Tamer YILMAZ Near East University Dental Faculty Director of Basic Medical Science Departmet What are vitamins? What are the structures of vitamin molecules? How many types of vitamins are there? Why are vitamin molecules necessary? Where are vitami...

Vitamins Prof. Dr. Tamer YILMAZ Near East University Dental Faculty Director of Basic Medical Science Departmet What are vitamins? What are the structures of vitamin molecules? How many types of vitamins are there? Why are vitamin molecules necessary? Where are vitamins used? What happens in vitamin deficiencies?  Vitamins Vitamins are necessary components of healthy diets. They play important roles in cellular metabolism. Vitamins are considered “micronutrients.” Although these substances occur in only very small amounts within cells, they are critically important. Their absence is usually manifested as some deficiency disease.  What are vitamins? Vitamins are organic compounds necessary in small amounts for the normal growth and function of humans and some animals. Vitamins are essential to life Vitamins are required for: – Growth – Maintenance – Reproduce – Regulation of body processes  What are vitamins? Vitamins are relatively small molecules. Most of them are coenzyme s.  Vitamins Water-soluble vitamins are stored in very small amounts in body. Therefore, do not accumulate to toxic levels. Fat-soluble vitamins can be deposited in human body. Therefore fat-soluble vitamins are toxic when taken continuously overloaded. This table is called hypervitaminosis.  Vitamins Absence in foods or malabsorption of vitamins results disorders. Insufficient of vitamins called hypovitaminasis or avitaminosis. İnsufficient –hypovitaminasis. Absence – avitaminosis. Multiple vitamin absence - polyavitaminosis.  Deficiency Vitamin deficiency occurs in some special cases: İnadequate feeding (continuous vomiting, incompleet teeth, etc) Malabsorption, steatorrhea, pancreatic insufficiency, gastrointestinal system abnormalities and surgery. Unavailability of stores. Increased excretion (kidney disease, pregnancy, lactation, diarrhea). Increased requirement (infectious disease, hyperthyroidism, pregnancy, growth, etc.)  13 different vitamins, each with its own roles. Vitamins grouped into two major categories: – Fat-soluble (4 fat soluble) Vitamin A Vitamin D Vitamin E Vitamin K – Water-soluble (9 water soluble: 8 B vitamins & C) Thiamin Riboflavin Niacin Biotin Pantothenic acid Vitamin B6 Folate Vitamin B12 Vitamin C  Vitamins Because vitamins are organic, they can be destroyed and left unable to function – Heat – keep refrigerated, don’t over cook – Light (ultraviolet) – store in opaque containers – Oxygen – after cut, keep airtight – Some water soluble – cook with less water The body needs vitamins in small amounts  Vitamins Other vitamins, originally designated as different, were later found to be the same compound. Vitamins H, M, S, W, and X were all eventually shown to be biotin. Vitamin G became B2 (riboflavin). Vitamin Y became B6 (pyridoxine). At one time, vitamin M seems to have been used for three different vitamins: folic acid, pantothenic acid, and biotin. Today, chemical names are used to help prevent confusion. commercial  Vitamin-Like Compounds Choline Carnitine Inositol Taurine Lipoic acid Synthesized in the body from amino acids and other nutrients. Digesting and Absorbing Water-Soluble Vitamins Digesting and Absorbing Vitamins  Water-soluble vitamins Found in watery parts of food. After absorbed move directly into blood. Transported freely in blood Not stored Need more regularly. Because no stored. Deficiency fast to develop because not stored. Generally toxicities can not seen. Usually no precursors Excreted with urine.  Vitamins B group Vitamin B1 (Thiamine) Vitamin B2 (Riboflavin) Vitamin B3 or Vitamin P or Vitamin PP (Niacin) Vitamin B5 (Pantothenic acid) Vitamin B6 (Pyridoxine and pyridoxamine) Vitamin B7 or Vitamin H (Biotin) Vitamin B9 or Vitamin M and Vitamin B-c (Folic acid) Vitamin B12 (Cyanocobalamin)  How should I study vitamins? What is the structure of this molecule?  How should I study What is the structure of this vitamins? molecule? What is the active form of this molecule?  How should I study vitamins? What is the structure of this molecule? What is the active form of this molecule? What is the function of this molecule?  How should I study vitamins? What is the structure of this molecule? What is the active form of this molecule? What is the function of this molecule? What are the symptoms of deficiency? What are the toxic symptoms?  Vitamin B1 (Thiamine) Composed of a substituted pyridine and thiazole ring. Thiamine (vitamin B1) was the first of the water- soluble B-vitamin family to be discovered.  Natural Sources It is found in all healthy plant and animal foods.  In mammalian cells: – Thiamine is converted to Thiamine Pyrophosphate Co-factor using ATP. Tiamin + ATP → TPP + AMP The active form of thiamine Thiamine Pyrophosphate It is an Co-enzyme for carbohydrates metabolism. This role enable conversion of blood sugar (glucose) into biological energy.  In mammalian cells: Thiamine pyrophosphate (TPP) is a coenzyme for: – Pyruvate dehydrogenase – α-ketoglutarate dehydrogenase These enzymes function in the metabolism of carbohydrates. – Transketolase Transketolase functions in: The pentose phosphate pathway to synthesize NADPH. The pentose sugars deoxyribose and ribose involved in nucleic acids biosynthesis.  Role of Thiamine It is an Co-factor for carbohydrates metabolism (Kreb’s Cycle). This role enable conversion of blood sugar (glucose) into biological energy.  Role of Thiamine This is important for: – Provide energy to the brain. – Improve transmission of nerve impulses through the nerves by providing them with energy. – Proper function of the heart muscles. – Healthy mucus membrane. – Maintenance of smooth and skeletal muscles. – Formation of red blood cells.  Causes of Deficiency A lack of thiamine can be caused by: Malnutrition. A diet high in thiaminase-rich foods (raw freshwater fish, raw shell fish, ferns) Foods high in anti-thiamine factors (tea, coffee, nuts). Chronic consumption of alcohol.  Deficiency Beriberi: The syndrome typically causes poor appetite, abdominal pain, heart enlargement, constipation, weakness, swelling of limbs, muscle spasms, insomnia, and memory loss (all reversed on treatment). Wernicke-Korsakoff syndrome: Resulted from untreated Beriberi and characterized by confusion, disorientation, inability to speak, numbness of extremities, edema, nausea, vomiting, visual difficulties, and may progress to psychosis, coma, and death. Even in advanced states, this condition can be reversible if B1 is given. omplication hissizlik giddiness  Interactions Oral contraceptives, antibiotics, sulfa drugs, and certain types of diuretics may lower thiamine levels in the body. Taking this vitamin may also intensify the effects of neuromuscular blocking agents that are used during some surgical procedures. B vitamins are best absorbed as a complex, and magnesium also promotes the absorption of thiamine drug  Vitamin B2 Riboflavin, lactoflavin, Vitamin G It chemically has a three rings structure (isoalloxazine) linked to ribityl moiety. Riboflavin is a yellow to orange - yellow powder, soluble in water. derivated Stability Vitamin B2 is unstable to light in both acidic and basic medium. Under acidic condition light produce lumichrome. In alkaline PH light produce lumiflavin. Both are inactive biologically.  Role of Vitamin B2 Riboflavin using as a coenzyme in cell. Riboflavin is converted to the active forms before using: – First coenzme FMN – Flavin-Mono Nucleotide Riboflavin-Monophosphate (FMN). Riboflavin + ATP FMN (phosphate bound ribitol )+ADP  Role of Vitamin B2 – Flavin-Adenine Dinucleotide Riboflavin-Adenine Diphosphate (FAD). FMN + ATP FAD + PPi  Role of Vitamin B2 The Active forms work as co-enzymes for about 150 oxidation-reduction reactions involved in: – Carbohydrate, Proteins and fat metabolism – Activation of vitamin B12 and folate. – Protection of erythrocytes and other cells from oxidative stress.  Causes of Riboflavin Deficiency: Not getting enough of the vitamin from the diet. A result of conditions that affect absorption in the intestine. The body not being able to use the vitamin. An increase in the excretion of the vitamin from the body. Ariboflavinosis Symptoms of riboflavin deficiency: Cracked and red lips. Inflammation of the lining of mouth and tongue. Mouth ulcers, angular chelitis. Dry and scaling skin and iron-deficiency anemia. The eyes become bloodshot, itchy and sensitive to bright light.  Ariboflavinosis Angular cheilitis is an inflammatory lesion at the corner of the mouth. Usually associated with a fungal (Candidal) or bacterial (Staphylococcal) infection.  Risk Factors for Deficiency Smokers and alcoholics are at higher risk for deficiency as tobacco and alcohol suppress absorption. Birth control pills may possibly reduce riboflavin levels. Diabetics have a tendency to be low on riboflavin as a result of increased urinary excretion. Athletes, and anyone else with a high-energy output will need additional vitamin B2.  Vitamin B3 (Niacin, Niacinamide, Nicotinic acid, Nicotinamide, Vitamin P, Vitamin PP)  Role of Vitamin B3 Riboflavin is converted to the active forms before using. Niacin + PP-riboseP (phosphoribosyl-1-pirophosphate) NMN + PPi NMN + ATP Nicotinat Adenine Dinucleotide + PPi NAD + glutamine Nicotinamide Adenine Dinükleotide + glutamic acid  Role of Vitamin B3 It is act as co-enzyme in oxidation-reduction reactions. Catabolic reactions: NAD /NADH + Anabolic reactions: NADP /NADPH + Role of Vitamin B3  Deficiency Pellagra: A serious deficiency of niacin. The main results of pellagra can easily be remembered as "the three D's": Diarrhea, Dementia, Dermatitis, and Death. It is very rare now, except in alcoholics, strict vegetarians, and people in areas of the world with very poor nutrition.  Deficiency Milder deficiencies of niacin can cause dermatitis around the mouth and rashes, fatigue, irritability, poor appetite, indigestion, diarrhea, headache. Reddened area is irritated and inflammed yorgunluk döküntü Pellagra  Risk Factors for Deficiency – Vegans, and others who do not eat animal protein, should consider taking a balanced B vitamin supplement. – Others people under high stress, chronic illnesses, liver disease may need extra niacin and other B vitamins.  Risk Factors for Deficiency – People over 55 years old are more likely to have a poor dietary intake. – Certain metabolic diseases also increase the requirement for niacin. – Those who abuse nicotine, alcohol or other drugs are very frequently deficient in B vitamins.  Vitamin B5 (Pantothenic acid) It is a peptide substance composed of Pantoic acid and b-Alanine. It can be present as the Calcium salt or the Alcohol “Pantothenol”. ATP PPi ATP PPi  Role of Vitamin B5 This coenzyme is used in the transfer of different carbon groups. It is a part of Co-enzyme A that assists the following reactions: – Formation of Sterols (Cholesterol and 7-Dehydrocholesterol). – Glucose catabolism and synthesis. – Formation and destroying of Fatty acids. – Formation of Keto acids such as Pyruvic acid.  Pantothenic Acid Deficiency symptoms – Vomiting, nausea, stomach cramps – Insomnia, fatigue, depression, irritability, restlessness, apathy – Hypoglycemia, increased sensitivity to insulin Toxicity symptoms: none reported Uykusuzluk bitkinlik duyarsızlık Vitamin B6  Pyridoxal phosphate Pyridoxal Phosphate is the active form of Vitamin B6  Pyridoxal phosphate Pyridoxal Phosphate is the active form of Vitamin B6 Vitamin B6 is needed for more than 100 enzymes involved in protein metabolism. İt is necessary for the metabolism of amino acids. It is essential for the transaminasyon reactions.  Pyridoxal phosphate Besides Transamination, Pyridoxal phosphate participates in several other reactions as cofactor, including: Glycogenolysis Hem synthesis Decarboxylation Non-oxidative deamination  Role of Vitamin B6 It is also essential for red blood cell metabolism and hemoglobin formation. The nervous and immune systems need vitamin B6 to function efficiently. Vitamin B6 also helps maintain blood glucose within a normal range. When caloric intake is low vitamin B6 help to convert other nutrients to glucose to maintain normal blood sugar levels.  Vitamin B6 Deficiency Dietary deficiency, though rare, can develop because extensive processing can deplete foods of vitamin B6. Individuals with a poor quality diet or an inadequate B6 intake. Alcoholics because alcohol also promotes the destruction and loss of vitamin B6 from the body. Older people. Asthmatic children treated with theophylline because it decreases body stores of vitamin B6. dru  Deficiency Deficiency symptoms Signs of vitamin B6 deficiency include: Skin: Dermatitis (skin inflammation), Stomatitis (inflammation of the mucous lining of any of the structures in the mouth), Glossitis (is inflammation or infection of the tongue). Neurological abnormalities: Depression, confusion, and convulsions. Vitamin B6 deficiency also can cause anemia. İnvoluntary spasm  Vitamin B7 (Vitamin H, Biotin, Growth Factor, Co-enzyme R) It is 2-Imidazolidinone tetrahydrothiophene-4- valeric acid.  Role of Vitamin B7 Biotin functions as a cofactor that aids in the transfer of carboxyl (COO) groups to various target macromolecules. Important for carbon dioxide fixation. In humans, biotin is involved in important metabolic pathways such as gluconeogenesis, fatty acid synthesis, glycogen synthesis and amino acid catabolism.  Biotin Deficiency symptoms – Depression, lethargy, hallucinations, numb or tingling sensation in the arms and legs – Red, scaly rash around the eyes, nose, and mouth – Hair loss – Skin lesions – Retarded growth Uyuşukluk ürpermek isilik ail fracture warp scurfy hair  Folic acid, Vitamin B9 (Vitamin M, Vitamin B-c) Conjugate of Pteridine, p- Aminobenzoic acid and Glutamic acid. Pteridine + p-aminobenzoic acid = Pteroic acid  Role of Vitamin B9 Active form of this vitamin is tetrahydrofolate H4 folate is short name of this vitamin. Folate reduced to dihydrofolate (DHF) and then to tetrahydrofolate (THF) within liver cells, by dihydrofolate reductase (DHFR) and NADH.  Role of Vitamin B9 Also a methyl group binds H4 folate in liver. Methyl H4 folate find in blood.  Folate THF act as Co-enzyme for: Leucopoiesis (Production of Leukocytes). Erythropoiesis (Production of Erythrocytes) DNA synthesis Neurotransmitter formation Those are the title of its effect  Role of Vitamin B9 The only function of folate coenzymes in the body appears to be in mediating the transfer of one carbon units.  Role of Vitamin B9 Folate coenzymes act as acceptors and donors of one-carbon units in a variety of reactions critical to the metabolism of nucleic acids and amino acids. Essential for synthesis of ATP, GTP, TMP serine and methionine amino acids. Essential for synthesis heme, the iron containing substance in haemoglobin.  Role of Vitamin B9 Form Reaction________ Methyl-THF Methionine synthesis Methylene-THF Thymidine mono- phosphate synthesis Formyl-THF Purine biosynthesis Formimino-THF Different intermediate reaction Methenyl-THF  In DNA metabolism Folate coenzymes play a vital role in DNA metabolism through two different pathways: The synthesis of DNA from its precursors (thymidine and adenine, guanine purines) is dependent on folate coenzymes.  Folik acid is released with this reaction. Formyl group bound the release H4 folate molecule and used in the purine (adenine, guanine) synthesis.  Role of Vitamin B9 Folate coenzymes are required for the metabolism of several important amino acids. The synthesis of methionine from homocysteine requires a folate coenzyme as well as a vitamin B12- dependent enzyme.  Role of Vitamin B9 Thus, folate deficiency can result in decreased synthesis of methionine and a buildup of homocysteine. Increased levels of homocysteine may be a risk factor for heart disease as well as several other chronic diseases.  Role of Vitamin B9 Proper formation of the brain, spinal cord, and nerve cells in the embryo. Closure of the neural tube in the fetus can not be completed without it. Kapanma  Neural Tube Defects Spina bifida: Literally means “split spine.” Spina Bifida happens when a baby is in the womb and the spinal column does not close all of the way. Anencephaly: Anencephaly is the absence of a major portion of the brain, skull, and scalp that occurs during embryonic development. Importance of folate before and during pregnancy. Government requires folate enrichment of flour and cereal. May prevent 50% neural tube defects spinal cord  Deficiency Very rare due to: Malabsorption (due to alcoholism). Impaired Hepatic functions (due to alcoholism). Pregnant women Alcoholics  Deficiency of Folate Similar signs and symptoms of vitamin B-12 deficiency. Megaloblastic anemia – RBC grow, cannot divide – Megaloblast: large, immature RBC Glossitis (is inflammation or infection of the tongue). Leucopenia  Vitamin B12 (Cyanocobalamin, Antipernicious anemia factor) Vitamin B12, is also called cobalamin, cyanocobalamin and hydroxycobalamin It is built from : Vitamin B12 A nucleotide and a complex tetrapyrrol ring structure (corrin ring) 1.A cobalt ion in the center. 2.A R- group persents bound to the Cobalt  Vitamin B12 When R is cyanide (CN), vitamin B12 takes the form of cyanocobalamin. (Commercial form) In hydroxycobalamin, R equals the hydroxyl group (-OH) (intermediate form of vitamin). detach  Vitamin B12 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 exclusively by microorganisms (bacteria, fungi and algae) Not by animals It is found in the liver of animals bound to protein as methycobalamin or 5'- deoxyadenosylcobala min. till-now  Vitamin B12 İn food B12 bound protein molecule. When the protein-B12 complex reaches the stomach, the stomach secretes acids and pepsine enzymes that detach the B12 from the protein. Then, in a process unique to B12, another protein, R-protein (glycoprotein haptocorrin) which protects it from gastric acid. picks up the B12 and transports it through the stomach and into the small intestine. R-protein is found in many fluids in the human body including saliva and stomach secretions.  Vitamin B12 The stomach cells also produce a protein called intrinsic factor (IF), which travels to the small intestine. When the B12-R-protein complex gets to the small intestine, the B12 is liberated from the R-protein by enzymes made by the pancreas. Of the liberated corrinoids, only the cobalamins attach to intrinsic factor. Intrinsic factor then carries the cobalamins to the last section of the small intestine, the ileum.  Vitamin B12 The cells lining the ileum contain receptors for the cobalamin-IF complex. The cobalamin-IF complex protects the cobalamin against bacterial and digestive enzyme degradation. The IF-receptor also ensures that cobalamins will be given priority for absorption over non-cobalamin corrinoids.  Vitamin B12 Transport in the Blood After B12 is absorbed into the intestinal cells, it attaches to transcobalamin II (TC2). Transcobalamin II is made in the intestinal cells where it picks up B12 and transports it to all body tissues through the blood and cerebrospinal fluid. Cyanocobalamin appears in the blood no longer than 5 hours after ingestion of B12.  Vitamin B12 Once the B12-TC II complex arrives at the cell where it is needed, B12 is released from TC II in the form of hydroxocobalamin. In the cytosol it is then turned into methylcobalamin. Or it can enter mitochondria and be converted to adenosylcobalamin and used for their respective enzymes.  Vitamin B12 functions Only two reactions in the body 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 end product of those chemical rections are propionyl-CoA. Excess remnant  Vitamin B12 functions The resultant propionyl-CoA is converted to succinyl-CoA for oxidation in the TCA cycle. – methylmalonyl-CoA mutase, requires vitamin B12 as a cofactor in the conversion of methylmalonyl-CoA to succinyl-CoA. – 5'-deoxyadenosine cobalamin is required for this reaction. Excess remnant xcess remnant derivated xcess remnant derivated  Vitamin B12 functions 2. The second reaction catalyzed by methionine synthase converts homocysteine to methionine. This reaction results in the transfer of the methyl group from N5- methyltetrahydrofolate to hydroxycobalamin generating tetrahydrofolate and methylcobalamin during the process of the conversion.  Vitamin B12 functions 2. The second reaction catalyzed by methionine synthase converts homocysteine to methionine. obtain  Deficiency symptoms: Pernicious anemia in humans: Pernicious Anemia: It is a type of Megaloblastic anemia characterized by decreased number of enlarged red blood cells. Inability to absorb B12 because of lack of gastric intrinsic factor – Congenital pernicious anemia. Inability to absorb B12 because of lack of HCl - Juvenile pernicious anemia.  Deficiency symptoms: Neurological disorders due to progressive demyelination of nerve cells. – This results from increase in methylmalonyl- CoA. – Methylmalonyl-CoA is a competitive inhibitor of malonyl-CoA in fatty acid biosynthesis. – Neurological changes such as numbness and tingling in the hands and feet. – Demyelination and irreversible nerve cell death. – Difficulty in maintaining balance, depression, confusion, dementia, poor memory. – In infants cause movement disorders and delayed development  Vitamin C (Ascorbic acid, Anti- Scurvy) Vitamin C is a water-soluble vitamin. Vitamin C was first isolated in 1928 and in 1932 it was proved to be the agent which prevents scurvy.  Vitamin C Vitamin C is a weak acid, called Ascorbic acid. Commercial vitamin C is often a mix of Ascorbic acid, Sodium ascorbate and/or other ascorbates.  Vitamin C It occurs as a white or slightly yellow crystal or powder with a slight acidic taste. It is an antiscorbutic product. On exposure to light, it gradually darkens. In the dry state, it is reasonably stable in air, but in solution it rapidly oxidizes. Ascorbic acid (vitamin c) is freely soluble in water; sparingly soluble in alcohol; insoluble in chloroform, in ether, and in benzene.  Vitamin C Ascorbic acid is reversibly oxidized to L- Dehydroascorbic acid. Both ascorbic and dehydroascorbic acids are physiologically active forms of vitamin C. Ascorbic acid is strong reducing agent, serves as an anti-oxidant and co- factor in hydroxylation reactions.  Vitamin C Further oxidation of L- Dehydroascorbic acid to 2,3-Diketo- gluconic acid is irreversible.  Role of Vitamin C It is a cofactor in the synthesis of norepinephrine from dopamine. Vitamin C is also involved in a variety of metabolic processes including oxidation-reduction reactions and cellular respiration, carbohydrate metabolism, synthesis of lipids and proteins. Vitamin C are attributed primarily to antioxidant and free radical scavenging effects that maintain proper immune system.  Role of Vitamin C Involved in the synthesis of Collagen the major component of ligaments, tendons, cartilages and skin. A well-known function of vitamin C is the role it plays in hydroxylation reactions that are essential for the formation of collagen. Vitamin C is important in collagen formation auricle cartilage  Role of Vitamin C T-lymphocyte is increased by vitamin C. Involved in tyrosine metabolism. The vitamin is an important aid in the absorption and conversion of iron to its storage form. Bile acid formation, and hence cholesterol degradation are highly dependent on vitamin C.  Vitamin C deficiency Fatigue, personality changes, decline in psychomotor performance and motivation. Vitamin C deficiency over 3-5 months results in Scurvyi In infants, disease name is Möller Barlow.  Vitamin C deficiency Scurvy: In Adults: Scurvy leads to the formation of liver spots on the skin, spongy gums, and bleeding from all mucous membranes. The spots are most abundant on the thighs and legs, and a person with the ailment looks pale, feels depressed, and is partially immobilized. Dişeti Solgun  Vitamin C deficiency Scurvy: In advanced scurvy there are open, suppurating wounds and loss of teeth. Severe scurvy may progress to neuritis, jaundice, fever, dyspnea, and death. Sarılık nefes darlığı  Vitamin C deficiency In infants, symptoms of Möller Barlow : anorexia, irritability, growth retardation, thigh tenderness, pseudoparalysis, bleeding around the lower ends of the leg bones (femur and tibia) causing pain. If left untreated, scurvy can proceed to collagen deficiency, seizures, shock or sudden death. yku hassasiyeti nöbet yalancı felç  Scurvy Scorbutic Rosary Follicular Hemorrhages  References Nelson D. L., Cox M.M. Lehninger Biyokimyanın İlkeleri. Palme Yayınevi. 2004. https://www.pdfdrive.com/lehninger-biyokimyan%C4%B1n-ilkeleri-t%C3%BCrk%C3%A7e-pdf-indir-e49744810.html Murray R. K.,et all. Harper’s Illustrated Biochemistry. Lange Medical Books/McGraw-Hill Medical. https://ia801208.us.archive.org/0/items/HARPERSILLUSTRATEDBIOCHEMISTRY30th/HARPER'S%20ILLUSTRATED%20BIOCH EMISTRY%2030th.pdf Wilson K., Walker J. Principles and Techniques of Biochemistry and Molecular Biology. 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