2 Vitamin C Vitamin C also known as ascorbic acid or ascorbate. The human being is one of the few mammals unable to synthesize vitamin C.Other animals unable to synthesize vitamin C include primates, fruit bats, guinea pigs, and some birds.The inability to synthesize vitamin C results from the lack of gulonolactone oxidase, the last enzyme in the vitamin C synthetic pathway.
3 History of Vitamin CVitamin C was isolated in 1928, and its structure was determined in 1933.The problems referred to as scurvy and associated with the lack of vitamin C had been quite prevalent for centuries. Some of the most notable stories are those of the British sailors who often died from scurvy on sea.
5 Vitamin CVitamin C have a number of vitamiers that have vitamin C activity in animals:Ascorbic acid in biological system (low pH)Oxidized form deyhroascorbic acid.Ascorbate in neutral salutation (pH>5)Ascorbate and ascorbic acid are both naturally present in the body, since the forms interconvert according to pH.
6 Sources Fruits, vegetables and organ meats (liver, kidney). The best food sources of vitamin C include asparagus, papaya, oranges, cantaloupe, cauliflower, broccoli, green peppers, grapefruit, grapefruit, lemons, and strawberries.Citrus products are most commonly cited as significant sources of the vitamin.Supplements supply vitamin C typically as free ascorbic acid, calcium ascorbate, sodium ascorbate, and ascorbyl palmitate.
7 Sensitivity of vitamin C Very significant losses occur as vegetables wilt, or when they are cut, as a result of the release of ascorbate oxidase from the plant tissue.Significant losses of the vitamin also occur in cooking, both through leaching into the cooking water and also atmospheric oxidation, which continues when foods are left to stand before serving.
8 DIGESTION, ABSORPTION & TRANSPORT Vitamin C does not require digestion prior to being absorbed into intestinal cells.There is active transport of the vitamin at the intestinal mucosal brush border membrane. Both ascorbate and dehydroascorbate are absorbed across the buccal mucosa by carrier-mediated passive processes.Intestinal absorption of dehydroascorbate is carrier mediated, followed by reduction to ascorbate before transport across the membrane.
9 DIGESTION, ABSORPTION & TRANSPORT Prior to absorption, ascorbic may be oxidized to dehydroascorbate, which may be absorbed by facilitated diffusion.Although dehydroascorbic acid is absorbed in higher rate than ascorbate, the amount of dehydroascorbic acid found in plasma and tissues under normal conditions is low, as cells rapidly reduce dehyroascorbic acid to ascorbate.
10 DIGESTION, ABSORPTION & TRANSPORT Simple diffusion (may occur in stomach and small intestine) provides for vitamin C absorption with ingestion of higher amounts of the vitamin.Anion channels in some cells may mediate vitamin C diffusion faster than the transporters.From intestinal cells, ascorbate may diffuses through anion channels into extracellular fluid and enters plasma by way of capillaries.
11 DIGESTION, ABSORPTION & TRANSPORT Within intestinal cells:Dehydroascorbic acid is rapidly reduced back to ascorbic acid by enzyme dehydroascorbate reductase.Glutathione (GSH), which is required for the reduction of dehydroascorbate, is oxidized in process. Glutathione spares vitamin C and, in general, improves the antioxidant protection capacity of blood.Degree of vitamin C absorption decrease with increased vitamin intake.
12 DIGESTION, ABSORPTION & TRANSPORT Some 80–95% of dietary ascorbate is absorbed at usual intakes (up to about 100 mg/day).The fractional absorption of larger amounts of the vitamin is lower, and unabsorbed ascorbate from very high doses is a substrate for intestinal bacterial metabolism, causing gastrointestinal discomfort and diarrhea.
14 DIGESTION, ABSORPTION & TRANSPORT Absorption of ascorbate may be diminished in the presence of high intracellular glucose, which appears to interfere with ascorbate transporter.Unabsorbed vitamin C may be metabolized by intestinal flora.Ingesting large amounts of iron with vitamin C may result in oxidative destruction of vitamin C in digestive tract, yielding other products without vitamin C activity.
15 DIGESTION, ABSORPTION & TRANSPORT In plasma:Ascorbic acid is transported in the plasma primarily in free form as an ascorbate anion.Normal plasma level of vitamin C 0.4 – 1.7 mg/dL.In cells:Uptake of ascorbate into body cells requires sodium and a carrier and into some cells such as leukocytes, uptake is also energy dependent.Tissue concentrations of vitamin C usually exceed plasma concentrations.
16 DIGESTION, ABSORPTION & TRANSPORT Ascorbate and dehydroascorbate concentrations are much greater in some tissues than others. The highest in adrenal and pituitary glands (~30-50mg/100 g of wet tissue).Intermediate in liver, spleen, heart, kidneys, lungs pancreas and leukocytes.Smaller amounts in muscles and red blood cells.Maximal vitamin C pool is estimated at about 1.500mg.Intakes of about mg vitamin C/d have been shown to produce plasma concentrations of about 1.0mg/dL and to maximize body pool.
17 Summary of absorptionAbsorbed in the intestine by an energy-requiring, sodium- dependent, carrier- mediated transport system.After absorption, ascorbic acid is then transported as a free acid in plasma into the cells, including leukocytes and red blood cells.In the tissues, Vitamin C serves as an electron donor for a number of enzymes.
18 Function & mechanism of action Vitamin C has very complex functional roles in the body as a cofactor in around eight reactions:Collagen synthesisCarnitine synthesisTyrosine synthesis and catabolismNeurotransmitter synthesis.Drug and steroid metabolism.Maintain the iron and copper atoms in the metalloenzymes in the reduced state.In addition vitamin C acting role as reducing agent in enzymatic reactions.Ascorbate may also act as an antioxidant against oxidative stress.
19 Collagen Synthesis Most abundant protein found in the body. Vitamin C is necessary for collagen synthesis.Collagen is a structural protein found in skin, bones, tendons, and cartilage.All collagen (n~19) have a triple helical structure.For the collagen molecule to aggregate into its triple-helix configuration selected proline residues must be hydroxylated forming hydroxyproline.Requires di-oxygenase enzymes, reduced iron (Fe+2), ascorbate.Vitamin C role:During hydroxylation, iron cofactor in the enzymes is oxidized, (ferrous(2+) state ---- ferric (3+) state).Ascorbate is needed to function as a reductant thereby reducing iron back to its ferrous (2+) in prolyl and lysyl hydroxylases.
20 Collagen SynthesisVitamin C may also influence mRNA levels needed for collagen synthesis.Although these reactions may seen simple, normal development and maintenance of skin, tendons, cartilage, bone and dentine depend on an adequate supply of vitamin C.Also, important in wound healing and bleeding prevention from capillaries.
22 Carnitine synthesisCarnitine is a methylated from nitrogen containing compound made from lysine.Sufficient carnitine is critical in fat metabolism, because it is essential to transport long- chain fatty acids from cell cytoplasm into mitochondrial matrix where β-oxidation occurs.Vitamin C role:Required for 2 hydroxylation reaction in synthesis carnitine, which functions as preferred reducing agent, specifically reducing Fe from ferric (Fe3+ ) back to ferrous state (Fe2+ ).
23 Tyrosine synthesis & catabolism Hydroxylation of phenylalanineRequires phenylalanine mono-oxygenase (hydroxylase), Fe+2. O2. tetrahydrobiopterin, NADPH, vitamin CVitamin C regenerating tetrahydro-biopterin from dihydrobiopterin.Occurs in liver and kidney.Tyrosine catabolism require ascorbate as reductant for hydroxylasesCu-dependent enzyme p-hydroxyphyenylpyruvate (dioxygenase)Fe-dependent enzyme homogentisate dioxygenase.
24 Neurotransmitter synthesis Vitamin C maintains mineral cofactors for some of the enzymes involved in synthesis of neurotransmitters in its reduced state.NorepinephrineIt is generated from hydroxylation of dopamine side chain.This reaction catalyzed by dopamine monoxygenase (contain 8 Cu atoms)-vitamin C- dependent reaction.Found in nervous tissue and adrenal medull.
26 Neurotransmitter synthesis SerotoninHydroxylation of tryptophan (in brain)Requires tryptophan mono-oxygenase (hydroxylase), O2 tetrahydrobiopterin, vitamin C. first step in serotonin synthesis.Other Neurotransmitters and Hormoneskeeping Cu in reduced for peptidylgycine α-amidating mono-oxygenase.Many of amidated peptides are active as hormones, such as calcitonin, CCK and gastrin.The enzyme found in pituitary , adrenal, thyroid glands and brain.
27 Summary Vitamin C acts as an electron donor for 8 different enzymes: Three enzymes participate in collagen hydroxylation.Two enzymes are necessary for synthesis of carnitine.Three remaining enzymes have the following functions in common, but have other functions as well:Dopamine β-hydroxylase participates in biosynthesis of norepinephrine from dopamine.Enzyme adds amide groups to peptide hormones.One modulates tyrosine metabolism.
28 Microsomal metabolism A group of enzymes makes up a microsomal metabolizing system, mostly function in liver, to inactivate both endo-and exogenous substances.Endogenous: Include various hormones and steroids (cholesterol)Exogenous: xenobiotics (foreign chemicals) drugs, carcinogens, pesticides, pollutants, food additivesThe reactions to metabolize these substances usually involve hydroxylation's followed by other reactions to produce polar metabolites for excretion.
29 Antioxidants activity The reduction potential of ascorbate is such that it readily donates electrons/hydrogen ions to regenerate other antioxidants, such as vitamin E, glutathione, and uric acid, and to reduce numerous reactive oxygen (ROS) and nitrogen species (RNS).Ascorbic acid interact with oxidants in the aqueous phase (blood or intracellular) before they initiate damage in nucleus, cell lipids.Ascorbate = thiols > bilirubin > uric acid > vitamin E
30 Pro-oxidant activityVitamin C can reduce transition metals, while itself becoming oxidized to semidehydroascorbate:Ascorbate (AH2) +Fe3+ or Cu2-Semidehydroascorbate radical (AH−) + Fe2+ or Cu1+These reduced metal ions can cause cell damage by generating ROS and free radicals.Fe2+ or Cu1+ + H2O Fe3+ or Cu2- + H2O2 + OHFe2+ or Cu1+ + O Fe3+ or Cu2- + O2-
31 Other functions Vitamin C and colds: Vitamin C is thought to moderate colds by enhancing many immune cell (such as some leukocyte) functions while also destroying histamine, which causes many of a cold’s symptoms.
32 Other functions Vitamin C and cancer: It is controversial issue due to:Epidemiological studies suggest inverse relationship between vitamin C and cancers of oral cavity, esophagus and stomach.Clinical studies:Some shown that survival time in cancer time patients may be prolonged, possible protective mechanismsAbility to act as a reducing agentDetoxify carcinogens.
33 Other functionsCVD:Many (but not all) epidemiological and prospective studies report that increased fruit and vegetable intake, vitamin C intake, and plasma vitamin C concentration are associated with decreased risk of heart disease.Low vitamin C status also is related to increased blood total cholesterol concentrations, whereas high plasma vitamin C concentrations have been associated with lower blood pressure and with higher plasma high-density lipoprotein cholesterol concentrations, both of which are protective against heart disease.studies with supplements of vitamin C and other antioxidants have not reported beneficial effects.
34 Other functions Cataracts: negative relation with vitamin c Bone density:Positive relation with vitamin CWound healing and connective tissue metabolism.
35 INTERACTIONS WITH OTHER NUTRIENTS Vitamin C and ironIncrease intestinal absorption of non-heme ironReduce Fe3+ to Fe2- forms a soluble complex with iron in alkaline pH of SI.Effect on iron distribution in the body.Vitamin C aids incorporation of iron into ferritinExcessive iron in presence of vitamin C can accelerate oxidative catabolism of vitamin C.
36 Interactions with other nutrients Vitamin C and copperMay increase absorption and excretion of heavy metalsVitamin C intakes above 600 mg/d may interfere with copper metabolism.Vitamin C helps keep folate in its reduced and active form.
37 Excretion Excretion reduced when intake is low Urinary excretion Body pool <1.500mg leads to only metabolites in urineBody pool > 1500mg leads to proportionately more ascorbate in urineVitamin C may be excreted intact or oxidized by L-ascorbate oxidase to oxalic acid, primarily in liver and some in kidney.
39 DeficiencyScurvyScurvy leads to formation of brown spots on skin, bleeding gums, small red skin discolorations caused by ruptured small blood vessels (petechiae), sublingual hemorrhages, easy bruising (ecchymoses and purpurae), impaired wound and fracture healing, joint pain (arthralgia), loose and decaying teeth, and hyperkeratosis of hair follicles, especially on the arms, legs, and buttocks.
41 Toxicity Toxicity is rare. Tolerable upper intake level of 2g vitamin C/dThe most common side effect with ingestion of large amounts (2 g) of the vitamin is gastrointestinal problems characterized by abdominal pain and osmotic diarrhea.Other side effects include increased risk of kidney stones and iron toxicity for those with renal disease and disorders of iron metabolism.