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BIOCHEMISTRY VITAMINS -STRUCTURE, FUNCTION, CLASSIFICATION, CLINICAL IMPORTANCE LEARNING OBJECTIVE At the end of lecture students should be able to: • Identify vitamins as micronutrients • Classify vitamins on basis of solubility • Describe general characteristics of water & lipid soluble vitamins in relation to sources, RDA, digestion & absorption, transport in blood, storage & excretion, function, toxicity, deficiency states. OVERVIEW OF VITAMINS WATER SOLUBLE • Dissolve in water • Readily excreted by kidney • Function as a coenzyme & in energy metabolism • Vitamin C, thiamin and riboflavin are especially susceptible to heat and alkalinity • Hydrophilic compounds and water leach them from vegetables • Marginal deficiency more common FAT SOLUBLE • Adsorbed with dietary fat in micelles • Excreted much more slowly • Stored in adipose tissue & liver so pose a greater risk of toxicity when consumed in excess • Chylomicrons containing fat-soluble vitamins are transported via the lymph to the bloodstream and evetually to the liver. CLASSIFICATION OF VITAMINS WATER SOLUBLE • Thiamin Pantothenic Acid • Riboflavin Biotin • Niacin Vitamin C • Vitamin B-6 • Folate • Vitamin B-12 FAT SOLUBLE • Vitamin A • Vitamin D • Vitamin E • Vitamin K THIAMIN FUNCTION • Sulfur containing and nitrogen containing rings attached to carbon atoms • Synthesize and regulate neurotransmitters • Functions in energy metabolism—vitamin portion of TPP; plays role in decarboxylation and helps form Acetyl Co A from pyruvate FOOD SOURCES • White bread, hot dogs, luncheon meat, cold cereal • Enriched grains/ whole grains • Thiaminase found in raw fish DEFICIENCY OF THIAMIN • Occurs where rice is the only staple • DRY BERIBERI – Weakness, nerve degeneration, irritability, poor arm/leg coordination, loss of nerve transmission • WET BERIBERI – Edema, enlarge heart, heart failure RIBOFLAVIN FUNCTIONS • Accepts electrons Electron Transport Chain FAD FADH2 Succinate ------- > Fumarate Citric Acid Cycle • Beta oxidation • Electron transport chain • Coenzymes: – Flavin mononucleotide (FMN) – Flavin adenine dinucleotide (FAD) • Oxidation-reduction reactions • Catabolism of fatty acids SOURCES • Enriched grains • Liver • Oyster • Brewer’s yeast • Sensitive to UV radiation (sunlight) • Most plant and animal foods • Milk and milk drinks and yogurt supply • Fortified cereals, bread and bread products contribute about 10% DEFICIENCY OF RIBOFLAVIN • Deficiencies are rare although some people may take in marginal amounts • Long term phenobarbital use, alcoholics, restricted caloric intake • Ariboflavinosis – Glossitis, cheilosis, seborrheic dermatitis, stomatitis, eye disorder, throat disorder, nervous system disorder • Occurs within 2 months • Usually in combination with other deficiencies FUNCTIONS OF NIACIN • Made from tryptophan • NAD and NADP participates in 200+ reactions in the body 2 NAD+ Glucose ---+ NAD Pyruvate - 2NADH + H+ - Pyruvate NADH + H+ -- NAD+ Isocitrate NADH + H+ NAD+ Alpha-ketogluterate NAD+ Malate • Lactate Alpha-ketogluterate NADH + H+ Succinyl CoA NADH + H+ - Oxaloacetate Electron transport chain DEFICIENCY OF NIACIN • Pellagra – Occurs in 50-60 days – Decrease appetite & weight • Food sources: mushrooms, enriched grains, beef, chicken, turkey, fish • Untreated corn as main staple • Hartnup disease • Alcoholics VITAMIN B6 FUNCTIONS • Names: Pyridoxal, Pyridoxine, Pyridoxamine • Main coenzyme form: pyridoxal phosphate (PLP) • Activate enzymes needed for metabolism of CHO, fat, protein • Transamination • Synthesis of hemoglobin and oxygen binding and white blood cells • Synthesis of neurotransmitters SOURCES • Meat, fish, poultry • Whole grains (not enriched) • Banana • Spinach • Avocado • Potato • Heat and alkaline sensitive DEFICIENCY OF VITAMIN B6 • Microcytic hypochromic anemia • Seborrheic dermatitis • Convulsion, depression, confusion • Reduce immune response • Peripheral nerve damage • Who is at risk? – Elderly – Alcoholics • Alcohol decreases absorption • Destroys the coenzyme form FOLATE • • • • Other names: Folic acid, Folacin Consists of pteridine group, para-aminobenzoic acid (PABA), and glutamic acid Coenzyme form: tetrahydrofolic acid (THFA) DNA synthesis – Transfer of single carbon units – Synthesis of adenine and guanine – Anticancer drug methotrexate • Homocysteine metabolism • Neurotransmitter formation DEFICIENCY OF FOLATE • Similar signs and symptoms of vitamin B-12 deficiency • Pregnant women • Megaloblastic anemia • Alcoholics – Interferes with the enterohepatic circulation of bile/folate • Neural tube defects - Spina bifida - Anencephaly • Importance of folate before and during pregnancy VITAMIN B12 FUNCTIONS • Coenzyme form: methylcobalamin, 5-deoxyadenosylcobalamin • Contains cobalt • Folate metabolism • Maintenance of the myelin sheaths • Citric Acid Cycle • RBC formation SOURCES • Synthesized by bacteria, fungi and algae • Stored primarily in the liver • Animal products • Organ meat • Seafood • Eggs • Hot dogs • Milk DEFICIENCY OF VITAMIN B-12 • Pernicious anemia – Never degeneration, weakness – Tingling/numbness in the extremities (parasthesia) – Paralysis and death – Looks like folate deficiency • Usually due to decreased absorption ability • Achlorhydria especially in elderly • Treatment: Injection of B-12 needed • Takes ~20 years on a deficient diet to see nerve destruction RISK FOR DEFICIENCY • Vegans • Breastfed infants of vegan moms • Elderly • Individuals with AIDS or HIV PANTOTHENIC ACID FUNCTIONS • Part of Coenzyme-A • Acyl carrier • Essential for metabolism of CHO, fat, protein SOURCES • Widespread in foods • Organ meats • Mushrooms • Whole grains • Avocado • Broccoli DEFICIENCY OF PANTOTHENIC ACID • Rare • Burning foot syndrome, fatigue, headache, sleep disturbance, nausea, abdominal distress • Alcoholics at risk • Usually in combination with other deficiencies BIOTIN FUNCTIONS • Free and bound form • Biocytin (protein bound form) • Biotinidase in small intestine • Carboxylation of acetyl-CoA to form malonyl-CoA for the elongation of a fatty acid chain • Addition of CO2 to pyruvate to yield oxaloacetate • Breaks down leucine • Allows 3 essential amino acids metabolism SOURCES • Widespread in foods • Organ meats, fish • Egg yolks • Soybeans • Whole grains DEFICIENCY OF BIOTIN • Rare • High intake of raw egg white diet • Alcoholics • Biotinidase deficiency • Anticonvulsant drug use • Signs & symptoms: skin rash, hair loss, convulsion, neurological disorders, impaired growth in children • • • • • • • VITAMIN C Ascorbic acid (reduced form), dehydroascorbic acid (oxidized form) Synthesized by most animals (not by human) Absorbed by a specific energy dependant transport system Passive transport if intake is high Decrease absorption with high intakes Easily lost through cooking Sensitive to heat, iron, copper, oxygen • Food sources: Citrus fruits, Potatoes, Green peppers, Cauliflower, Broccoli, Strawberries, Romaine lettuce, Spinach FUNCTIONS OF VITAMIN C • Antioxidant • Collagen synthesis • Stabilizes reduced form of folate enzyme • Enhances absorption of non-heme iron • Helps synthesize carnitine • Proper functioning of immune system • Deficiency cause: SCURVY • Scurvy : Breakdown gums and joints, Bone pain, diarrhea, fractures, fatigue • UL is 2,000 mg per day RETINOIDS: animal source • 3 forms of vitamin A important for health – Retinal – Retinoic acid – Retinol • β-carotene (a carotenoid or pigment) in yellow/orange foods is a potent provitamin A • • • • • CAROTENOIDS: plant source Serving as an ―antioxidant‖ Protecting from cancer (related to antioxidant function?) Protecting from heart disease? Supports immune system function VITAMIN A FUNCTIONS • Promote vision (retinal) • Participate in protein synthesis and cell differentiation • Support reproduction and growth • Support immunity (retinoic acid and carotenoids) • Involved in bone growth and remodeling • Synthesis of glycoproteins • Antioxidant activity (β-carotene) DEFICIENCY • Night blindness • Cell keratinization -Dry skin -Xerophthalmia (dryness of cornea & conjunctiva) • • • Abnormal skeletal development/maintenance Immune dysfunction Reproductive disorders -In females: -Increased abortions -Neonates born dead/weak -Deformed young: no eyeballs; hydrocephalus -In males: Keratinization of testicular epithelium HYPERKERATOSIS Uterus with stratified squamous epithelium with keratinization at surface Lung bronchus - lumen (top) filled with purulent exudate containing desquamated epithelial cells XEROPTHALMIA VITAMIN D FUNCTION • Vit. D2 ergocalciferol – Completely synthetic form produced by the irradiation of the plant steroid ergosterol • Vit. D3 :cholecalciferol – Produced photo chemically by the action of sunlight or ultraviolet light from the precursor sterol 7-dehydrocholesterol • Promotes calcium and phosphate • absorption and mobilization DEFICIENCY CHILDREN • Rickets -Results in ―bowed‖ legs or knock-knees, outward bowed chest and knobs on ribs ADULT • Osteomalacia Softening of bones, bending of spine, and bowing of legs • Osteoporosis Associated with fractures very serious for geriatrics VITAMIN E FUNCTIONS • Antioxidant: Free radical scavenger -Protects cell membranes -Protects LDL from oxidation -Protection of double bonds in polyunsaturated fatty acids -Works in conjunction with selenium • Stabilize reactions or situations that typically produce free radicals -Nucleic acid and protein metabolism, protecting DNA -Mitochondrial metabolism DEFICIENCY • Rare • Erythrocyte hemolysis and hemolytic anemia • Prolonged deficiency causes neuromuscular dysfunction; affects the spinal cord and the retina • Reproductive failure – Ovarian failure – Testes degeneration – Fetal resorption • Derangement of cell permeability – Liver, brain, kidney,blood capillaries – Brain necrosis (crazy chick diz) • Muscular lesions – Stiff lamb disease (skeletal muscle degeneration) • Failure to growth VITAMIN K FUNCTIONS Types K1, phylloquinone – Chloroplasts in plants K2, menaquinone – Bacterial synthesis K3, menadione - Synthetic, water soluble form • Clotting factors are synthesized in the liver as inactive precursors - vitamin K converts them to their active forms – Conversion of prothrombin to thrombin – Formation of fibrinogen to fibrin, leading to clot formation • Stimulates bone formation and decreases bone resorption DEFICIENCY • • • Primary deficiency rare Secondary deficiency: fat absorption is impaired(e.g., cystic fibrosis, Crohn’s disease) long-term or high-dose administration of antibiotics (they kill the bacteria in large intestine) Newborn babies with sterile GI tract; single vitamin K dose given to prevent hemorrhage Prolonged clotting time – Generalized hemorrhages REFERENCES • BIOCHEMISTRY, 5TH EDITION LIPPINCOTT’S ILLUSTRATED REVIEWS CHAPTER 28: VITAMINS Pg # 373-393 • Vitamins to be further referred in metabolism & respective functions
