1 WATER SOLUBLE VITAMINS Dr Vivek Joshi

2 Overview Vitamins are chemically unrelated organic compounds that cannot be synthesized in adequate quantities by humans and, therefore, must be supplied by the diet. Essential food factors Many vitamins act as cofactor- coenzymes or prosthetic groups for enzymes Required for growth, differentiation and maintenance of normal cellular function.

3 Classification of Vitamins

4 Comparison Fat Soluble VitaminsWater Soluble Vitamins ExamplesA,D,E,KB complex & C Soluble only inFatWater AbsorptionAlong with lipids, Require bile salts Simple, except B 12 Carrier proteinsPresentNot required StorageYes, in liverNot possible, except B 12 ExcretionUsually not excretedYes, mainly in urine DeficiencyRare, due to storageCommon & early, no storage ToxicityHypervitaminosisUnlikely Treatment of deficiencySingle large doseRegular dietary supply

5 Water-soluble Vitamins Thiamine (Vitamin B 1 ) Riboflavin (Vitamin B 2 ) Niacin (Vitamin B 3 ) Pantothenic Acid (Vitamin B 5 ) Pyridoxine (Vitamin B 6 ) Biotin (Vitamin B 7 ) Folic Acid, Folate (Vitamin B 9 ) Cobalamin (Vitamin B 12 ) Ascorbic Acid (Vitamin C) Reference Daily Intake (or Recommended Daily Intake) (RDI) is the daily dietary intake level of a nutrient which is considered to be sufficient to meet the requirements of healthy individuals.

6 Cofactors & Water soluble vitamins “A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity”. Cofactors can be considered "helper molecules" that assist in biochemical transformations. Cofactors can also be classified depending on how tightly they bind to an enzyme, with loosely-bound cofactors termed coenzymes and tightly- bound cofactors termed prosthetic groups. An inactive enzyme, without the cofactor is called an apoenzyme, while the complete enzyme with cofactor is the holoenzyme. All the water-soluble vitamins (except Vitamin C) are converted / activated to a cofactor.

7 Thiamine (Vitamin B 1 ) Thiamine pyrophosphate is the biologically active form. It serves as a coenzyme for (A) transketolase, and in the (B) oxidative decarboxylation in TCA cycle. RDA: 1.1 mg Ref: (A) Transketolase, an enzyme of the pentose phosphate pathway. It connects the pentose phosphate pathway to glycolysis. (B) Oxidative decarboxylation reactions are oxidation reactions in which a carboxylate (COOH) group is removed, forming carbon dioxide

8 Thiamine (Vitamin B 1 ) (contd.) Thiamine deficiency: Beriberi: Common in areas where polished rice is the major component of the diet. Wet beriberi affects the heart; it is sometimes fatal, as it causes a combination of heart failure and weakening of the capillary walls. Dry beriberi causes wasting and partial paralysis resulting from damaged peripheral nerves. Wernicke-Korsakoff syndrome: Seen in association with chronic alcoholism, is due to dietary insufficiency or impaired intestinal absorption of the vitamin. Characterized by apathy, loss of memory, and a rhythmical to-and-fro motion of the eyeballs (nystagmus). CVS CNS

9 Riboflavin (Vitamin B 2 ) The two biologically active forms are flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). FMN and FAD are important for flavoenzymes that catalyze the oxidation or reduction of a substrate. (electron transfer) Riboflavin deficiency is not associated with a major human disease, although it frequently accompanies other vitamin deficiencies. RDA: 0.5 mg/1000 kcals Deficiency symptoms include dermatitis, Cheilosis and glossitis (fissuring at the corners of the mouth and the tongue appearing smooth and purplish)

10 Niacin (Vitamin B 3 ) The biologically active coenzyme forms are nicotinamide adenine dinucleotide (NAD + ) and its phosphorylated derivative, nicotinamide adenine dinucleotide phosphate (NADP + ). NAD + and NADP + serve as coenzymes in oxidation- reduction reactions. (electron transfer) E.g. ETC, Citric acid cycle The reduced forms of NAD + and NADP + are NADH and NADPH, respectively. RDA: 6.6 mg/1000kcal

11 Niacin (Vitamin B 3 ) (contd.) Clinical indications for niacin: 1. Deficiency of niacin: Pellagra, a disease involving the skin, GIT, and CNS. The symptoms of pellagra progress through the 3 Ds: dermatitis, diarrhea, dementia— and, if untreated, death. 2. Treatment of hyperlipidemia: Niacin causes a decrease in plasma triglycerides (in VLDL) and cholesterol (in VLDL and LDL).

12 Pantothenic Acid (Vitamin B 5 ) Pantothenic acid is a component of Coenzyme A, which functions in the transfer of acyl groups. Role in the synthesis and oxidation of fatty acids. It is widely distributed. Pantothenic acid deficiency is very rare. RDA: 4-7mg Ref: Coenzyme A (CoA, CoASH, or HSCoA) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle (TCA cycle).

13 Pyridoxine (Vitamin B 6 ) Vitamin B 6 is a collective term for pyridoxine, pyridoxal, and pyridoxamine, all derivatives of pyridine. Biologically active coenzyme: pyridoxal phosphate. It functions as a coenzyme for a large number of enzymes, particularly those that catalyze reactions involving amino acids. RDA: 1.6-2mg Clinical indications for pyridoxine: Isoniazid, a drug used to treat tuberculosis, can induce B 6 deficiency. Otherwise, dietary deficiencies in pyridoxine are rare but have been observed in alcoholics, some newborn infants, women taking oral contraceptives. Only water soluble vitamin which leads to toxicity. Ref: Pyridoxine (alcohol form), pyridoxal (aldehyde form), and pyridoxamine (amine form)

14 Biotin (Vitamin B 7 ) Biotin is a coenzyme in carboxylation reactions. Carboxylation in is a chemical reaction in which a carboxylic acid group is introduced in a substrate Biotin deficiency is rare, because it is widely distributed in food & large quantity supplied by intestinal bacteria. RDA: µg Raw egg white contains a glycoprotein, avidin, which tightly binds biotin and prevents its absorption from the intestine. However, the addition of large quantities of raw egg white to the diet induces symptoms of biotin deficiency, namely, dermatitis, glossitis, loss of appetite, and nausea. It has been estimated that 20 eggs/day would be required to induce a deficiency syndrome. Thus, inclusion of an occasional raw egg in the diet does not lead to biotin deficiency.

15 Folic Acid (Vitamin B 9 ) Folic acid (or folate), which plays a key role in one-carbon metabolism. Essential for the biosynthesis of several compounds. The human body needs folate to synthesize and also repair DNA, important during periods of rapid cell division and growth Active form: Tetrahydrofolate (THF) Function: Tetrahydrofolate receives one-carbon fragments from donors and transfers them to intermediates in the synthesis of amino acids, purines, and thymidine monophosphate (TMP).

16 Folic Acid (Vitamin B 9 ) (contd.) Folic Acid- Deficiency: 1. Megaloblastic anemia: caused by diminished synthesis of purines and TMP, which leads to an inability of cells to make DNA and, therefore, they cannot divide. 2. Neural tube defects in the fetus: Spina bifida and anencephaly, the most common neural tube defects, affect approximately 4,000 pregnancies in the United State annually. Folic acid supplementation during pregnancy significantly reduce these defects. Ref: A megaloblast is an unusually large erythroblast that can be associated with pernicious anemia (Vitamin B12 deficiency) and folic acid deficiency (collectively called megaloblastic anemia). The neural tube is the embryo's precursor to the central nervous system, which comprises the brain and spinal cord.

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19 Cobalamin (Vitamin B 12 ) Key role in the normal functioning of the nervous system and for the formation of blood Required for two essential enzymatic reactions  Homocysteine to Methionine,  Methylmelonyl CoA to Succinyl CoA Vitamin B 12 is synthesized only by microorganisms; it is not present in plants. Animals obtain the vitamin from their intestinal bacterial flora or by eating foods derived from other animals. RDA: 1-3 µg

20 Cobalamin (Vitamin B 12 ) (contd.) Deficiency of Vitamin B 12 Pernicious anemia: Normally, vitamin B 12 obtained from the diet binds to intrinsic factor in the intestine. The bound cobalamin is transported into the intestinal mucosal cell and, subsequently, into the blood. Lack of intrinsic factor prevents the absorption of vitamin B 12, resulting in pernicious anemia. Advanced cases may also show neuropsychiatric symptoms.

21 Ascorbic Acid (Vitamin C) Main function: As a reducing agent in several important reactions. Coenzyme for collagen synthesis; therefore, required for the maintenance of normal connective tissue, as well as for wound healing. facilitates the absorption of dietary iron from the intestine. Antioxidant Deficiency: Scurvy, a disease characterized by sore and spongy gums, loose teeth, fragile blood vessels, swollen joints, and anemia. Ref: Collagen is a group of naturally occurring proteins, found exclusively in animals. It is the main protein of connective tissue. It is the most abundant protein in humans, making up about 25% to 35% of the whole-body protein content.

22 Vitamin & Other Names Active formBiological FunctionsDeficiency Thiamine B1Thiamine pyrophosphate Cofactor for enzyme catalyzing:  Transketolation  Oxidative decarboxylation  Beriberi  Wernicke- Korsakoff Syndrome (in Alcoholics) Riboflavin B2FMN, FADElectron transfer Rare.  Dermatitis  Stomatitis Niacin B3, Nicotinic Acid, Nicotinamide NAD +, NADP + Electron transferPellagra Pantothenic Acid B5 Coenzyme AAcyl transfer- Pyridoxine B6, Pyridoxamine, Pyridoxal Pyridoxal phosphate Cofactors for enzymes of amino acid metabolism  Glossitis,  Neuropathy Biotin B7Enzyme-bound biotinCarboxylation reaction Rare, Excessive Egg white may cause deficiency Folic Acid B9, Folate Tetrahydrofolic Acid  Transfer of one-carbon unit;  Synthesis of methionine, purines and thymidine monophosphate  Megaloblastic Anemia  Neural tube defects Cobalamin B12  Methylcobalamin  Deoxyadenosyl cobalamin Cofactors for reactions:  Homocysteine to Methionine,  Methylmelonyl CoA to Succinyl CoA  Pernicious Anemia  Dementia  Spinal degeneration Vitamin C, Ascorbic Acid  Cofactor for hydroxylation reaction in collagen  Antioxidant Scurvy