VITAMIN C

VITAMIN C

1. Vitamin C Gandham . Rajeev Department of Biochemistry, Akash Institute of Medical Sciences & Research Centre, Devanahalli , Bangalore, Karnataka, India. E-Mail: [email protected]

2. Vitamin C is a water soluble vitamin The use of vitamin C in megadoses to cure everything from common cold to cancer Chemically it is known as ascorbic acid Ascorbic acid is a hexose derivative & closely resembles monosaccharide's in structure Vitamin C exists in two forms L – ascorbic acid (reduces form) L – Dehydro ascorbic acid (oxidized form) Chemistry

3. The acidic property of vitamin C is due to the enolic hydroxyl group Vitamin C is strong reducing agent L – ascorbic acid undergoes oxidation to form dehydro ascorbic acid & it is reversible reaction

4. Ascorbic acid & dehydro ascorbic acid are biologically active D – ascorbic acid is biologically inactive Ascorbic acid is present in all tissue & plasma as reduced form Oxidation of ascorbic acid is rapid in the presence of copper

5. Vitamin C is heat labile In the process of cooking about 50% of vitamin passes to water & 20% is oxidized Biosynthesis of ascorbic acid: Many animals can synthesize ascorbic acid from glucose via uronic acid pathway Man , other primates, guinea pigs and bats cannot synthesize ascorbic acid due to deficiency of the enzyme L – gulonolactone oxidase

6. It is readily absorbed from stomach & small intestine Storage: Only small amounts of vitamin C are stored in the body (1 gm) It is present in the tissues as ascorbic acid & dehydro ascorbic acid Mainly found in retina, adrenal gland, pituitary & thymus Metabolism

7. Ascorbate 2-sulfate is urinary excretary form of ascorbic acid Oxalate is another metabolite & is excreted in urine Excretion

8. Coenzyme Forms Ascorbic acid ( reduced form) Dehydro ascorbic acid (oxidized form) Involves reversible oxidation – reduction reactions Interconversion of ascorbic acid to dehydro ascorbic acid Biochemical Functions

9. Proline hydroxylase: Proline hydroxylase catalyzes the hydroxylation of proline on collagen Ascorbic acid & ferrous iron are cofactors Ascorbic acid is essential to keep the iron in ferrous form It essential for maturation &cross-linking of collagen Collagen Formation

10. Proline Hydroxy proline Proline hydroxylase Ascorbic acid (Fe++) O 2 H 2 O Succinate α - Ketoglutarate

11. Lysine hydroxylase catalyzes the hydroxylation of lysine residues present on collagen (free lysine is not hydroxylated) Ascorbic acid & ferrous iron are cofactors Ascorbic acid is essential to keep the iron in ferrous form It essential for maturation &cross-linking of collagen Lysine hydroxylase

12. Hydroxylation occurs after the peptide chain synthesis (post-translational modifications) In vitamin C deficiency, collagen synthesis is defective , delayed wound healing It is administered after surgery to enhance wound healing Lysine Hydroxy lysine Lysine hydroxylase Ascorbic acid (Fe++) O 2 H 2 O Succinate α - Ketoglutarate

13. In tyrosine catabolism Parahydroxy phenyl- pyruvate hydroxylase catalyzes the formation of homogentisic acid form parahydroxy phenyl pyruvate Ascorbic acid is required for this reaction Parahydroxy phenyl- pyruvate hydroxylase Parahydroxyphenyl pyruvate Homogentisic acid Parahydroxy phenylpyruvate hydroxylase Ascorbic acid (Cu ++) O 2

14. In catecholamine synthesis Dopamine β oxidase catalyzes the formation of norepinephrine from dopamine This is essential for synthesis of catecholamines Adrenal medulla is rich in vitamin C Dopamine β oxidase (dopamine hydroxylase) Dopamine Norepinephrine Dopamine β oxidase Ascorbic acid

15. Ferrochelatase catalyzes the formation of heme from protoporphyrin IX Vitamin C is necessary for the incorporation of Fe++ into protoporphyrin IX to form heme Vitamin C keeps the iron in ferrous form Iron & Heme metabolism Protoporphyrin IX Heme Ferrochelatase Ascorbic acid , Fe++

16. In the biosynthesis of bile acids Cholesterol 7 α – hydroxylase catalyzes the formation of 7 α – hydroxycholesterol from cholesterol In this vitamin C is a cofactor It is a rate limiting step in bile acid synthesis Cholesterol 7 α - hydroxylase Cholesterol Cholesterol 7 α hydroxylase NADPH + H+ NADP 7 α - hydroxy Cholesterol Ascorbic acid

17. Bone tissues possess an organic matrix, collagen & inorganic calcium & phosphate Vitamin C is required for bone formation Tryptophan metabolism: Ascorbic acid is necessary for the hydroxylation of tryptophan to 5-hydroxytryptophan It is required for the formation of serotonin Bone formation

18. Iron metabolism: Ascorbic acid increases the iron absorption from the intestine Ascorbic acid reduces ferric iron to ferrous state , which is commonly absorbed Folic acid metabolism: Vitamin C needed for the formation of FH 4 In association with FH 4 , it is involved in maturation of RBC

19. Peptide hormone synthesis: Hydroxylation of glycine is carried out by peptidyl glycine hydroxylase which requires vitamin C Steroid synthesis: Adrenal gland possesses high levels of ascorbic acid Ascorbic acid is necessary for hydroxylation reactions in the synthesis of corticosteroid hormones

20. Sparing action of other vitamins: Ascorbic acid is a strong antioxidant It spares vitamin A, E and some B-complex vitamins from oxidation Immunological function: Vitamin C increases the synthesis of immunoglobulins & increases the phagocytic action of leucocytes

21. Cataract: Vitamin C is concentrated in the lens of eye Regular intake of ascorbic acid reduces the risk of cataract formation Anti-oxidant property: Vitamin C is an antioxidant It reduces the risk of cancer, coronary heart diseases

22. Rich sources are fruits & vegetables such as lemon,oranges , grapes, spinach and tomatoes Milk is a poor source of vitamin Men 60 mg/day Women 60 mg/day Pregnancy 80 mg/day Lactation 100 mg/day Dietary sources RDA

23. Inadequate intake mainly caused by dietary deficiency Impaired absorption is due to intestinal diseases Increased demand of vitamin C is seen in pregnancy, lactation, surgery and burns Features: The deficiency of ascorbic acid results in scurvy Deficiency

24. Infantile scurvy (Barlow’s disease) In infants between 6 to 12 months of age, diet should be supplemented with vitamin C sources Hemorrhagic tendency: In ascorbic acid deficiency, collagen is abnormal & the intracellular cement substance is bretile So capillaries are fragile, leading to the tendency to bleed even under minor pressure

25. Petechial hemorrhages: Due to rupture of capillaries, resulting from lack of intracellular substances Ecchymoses or even hematoma in severe conditions Internal bleeding: In severe cases, hemorrhage may occur in the conjunctiva & retina

26. Oral cavity: In severe cases of scurvy, the gums becomes painful, swollen & spongy The pulp is separated from the dentine and finally teeth are lost Wound healing may be delayed Bones: In the bones, the deficiency results in the failure of the osteoblasts to form the intracellular substance, osteoid

27. Without the normal ground substance, the deposition of bone is arrested The bones become weak and fractures easily Hemorrhage into joint cavities Vitamin C & vitamin B are essential nutrients to maintain bone density & bone quality

28. Anemia In vitamin C deficiency deficiency , normochromic , normocytic (due to bleeding), megaloblastic ( due to reduced erythropoiesis ) and microcytic hypochromic anemia (due to impaired iron absorption & impaired heme synthesis) are seen Fatigue, depression, & susceptibility to infections are associated with vitamin C deficiency

29. The beneficial effect of vitamin C is used in the treatment of TB Clinical dose is 500 mg/day Vitamin C is recommended for treatment of ulcer, trauma and burns Toxicity of vitamin C: Excess vitamin C is excreted, and is not accumulated in the body More than 2000 mg may cause iron over load Therapeutic use of vitamin C

30. Decreased plasma, platelet and leukocyte ascorbic acid levels Biochemical findings

31. References Harper’s Biochemistry 25 th Edition. Fundamentals of Clinical Chemistry by Tietz. Text Book of Medical Biochemistry-A R Aroor. Text Book of Biochemistry-DM Vasudevan Text Book of Biochemistry-MN Chatterjea Text Book of Biochemistry-Dr.U.Satyanarana