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by M. Mandengeby M. Mandenge 11
Vitamin C :DeficiencyVitamin C :Deficiency( Scurvy)( Scurvy)
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Vitamin C : StructureVitamin C : Structure
Vitamin C
Black is carbon, red is oxygen, and white is hydrogen
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BackgroundBackground
Vitamin C a.k.a. Ascorbic acid Essential nutrient for
higher primate,few mammals (notably guinea pigs &bats),few bird species and
some fish Most animals & plants synthesize own
sequence of four enzyme driven steps , converting glucoseto vitamin C
Glucose for Vitamin C production in animalsextracted from glycogen
In mammals & some birds - liver In reptiles & most birds - kidneys Humans - no enzymatic capability to make
due to a defect in gene for the last enzyme(L-gulonolactone oxidase) in synthesis process, mustSUPPLEMENT in diet.
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Structural formsStructural forms
LL--ascorbate(oxidized form) Lascorbate(oxidized form) L--dehydroascorbatedehydroascorbate
Vitamin C/ascorbic acid/L-ascorbate is purely of the L-enantiomer of ascorbate.
D-enantiomer - no physiological significance
L-ascorbate is a strong reducing agent & is oxidised to L-dehydroascorbate
L-dehydroascorbate reduced back to active L-ascorbateform by enzymes & glutathione so not all is lost.
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Importance/Function:Importance/Function:
Antioxidant - lessen oxidative stress - alongsideenzyme glutathione peroxidase to revitalize vit. E(fat-soluble) to stop free radical chain reactions influids & indirectly in lipids.
A substrate for ascorbate peroxidase
Enzyme cofactor for biosynthesis Electron donor for eight different enzymes;
2 needed for carnitine synthesis essential forfatty acid transport into mitochondria for ATPgeneration
cofactor for (epsiloncofactor for (epsilon--NN--trimethyllysinetrimethyllysine hydroxylasehydroxylase andandgammagamma--butyrobetainebutyrobetaine hydroxylasehydroxylase))
One modulates tyrosine metabolismOther enzymes add amide groups to peptide
hormones, increasing stability.
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Importance/Function:Importance/Function:
3 involved in collagen hydroxylation;
{prolyl 4-hydroxylase,
prolyl 3-hydroxylase and
lysyl hydroxylase}
add OH to amino acids proline & lysine in collagensubunits allowing the collagen molecule to assumeits triple helix structure(see slide8)
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FunctionFunction
serves as a natural aspirin, by combating inflammation andserves as a natural aspirin, by combating inflammation andpainpain-- accomplishes this by inhibiting secretion of theaccomplishes this by inhibiting secretion of theprostaglandins that contribute to such symptoms.prostaglandins that contribute to such symptoms.
inhibitsinhibits aldosealdose reductasereductase -- converts glucose toconverts glucose to sorbitolsorbitol --
accumulation associated with development of diabeticaccumulation associated with development of diabeticcomplications incl. cataracts,complications incl. cataracts, retinopathy &retinopathy & neuropathy.neuropathy.
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88Figure . Flowchart of collagen biosynthesis
Vitamin C required
for hydroxylation
Vitamin C required toexport procollagen
out of cell
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Collagen Hydroxylation
Procollagen polypeptide chains made on ribosomes of rough ER andsecreted into lumen, where modified by hydroxylation of certain
proline and lysine residues and glycosylation before chain associationand triple helix formation
Vitamin c as e
lectrondonor
Vitamin C to exportprocollagen out ofcell
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Significance of collagenSignificance of collagen
Most abundant protein in the body, collagen accountsfor more mass than all other proteins put together.
forms connective fibres
in skin, ligaments, cartilage, bones and teeth.
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Vitamin C Deficiency : ScurvyVitamin C Deficiency : Scurvy
Recommended Daily Allowance >100mg
Body able to store a minimum amount & if notsupplemented becomes depleted.
Prolonged deficiency of vitamin C results in SCURVY!!
Scurvy clinical signs take 4 to 8 months to develop.
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Most Susceptible individualsMost Susceptible individuals
Babies of mothers taking high doses of vitamin Cduring pregnancy
Bottle fed babies Vitamin C decomposed bypasteurization (melt point 190 C)
Using repetitive cooking methods decomposed at 190C
{Elderly people,
Alcoholics } poor eating habits Factors increasing Vitamin C requirements are viral
illness & fever e.g.. INFLUENZA
-respiratory burst - level of ascorbic acid inlevel of ascorbic acid inleukocytes may be 80x > found inleukocytes may be 80x > found inplasma.plasma.
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Respiratory BurstRespiratory Burst
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bacteria recognized as foreign and coated with molecules - opsonization
After engulfing bacterium, neutrophil
granules fuse with membrane of corralled
pathogen whereby toxic chemicals reach it.Leukocytes take up lots of oxygen (called a
respiratory burst) to produce certain of
these toxic chemicals
Ascorbic acid stimulates thehexose monophosphate (HMP)shunt- reduces coenzyme NADPto NADPH. Phagocytes needNADPH to create superoxide +other reactive oxygen speciesused to destroy pathogens.
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Most Susceptible individualsMost Susceptible individuals
Diabetics Vitamin C competes with glucose to reachtissues & organs through a commoncellular transport system.
Insulin moves both glucose and ascorbic acidInsulin moves both glucose and ascorbic acid
constantly competing for insulin transport soconstantly competing for insulin transport sodiets high in sugar and carbohydrates decreasediets high in sugar and carbohydrates decreaseamount of ascorbic acid entering cellsamount of ascorbic acid entering cells
Insufficient insulin supply can inhibitvitamin C transport to cells.
Smokers - One estimate suggests cigarette smokeOne estimate suggests cigarette smokecontains on the order of 10contains on the order of 101414 free radicals perfree radicals perinhalation.inhalation.
Free radicals capable of inducing oxidativeFree radicals capable of inducing oxidativestress.stress.
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Scurvy !!!Scurvy !!!
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ScurvyScurvy
Synthesized collagen is too unstable to
perform function
Leads to formation of liver spots on skin especiallyon thighs & legs
Pain & tenderness of legs
Exhaustion and general weakness
Spongy gums , loose teeth & bleeding from allmucous membranes
Loss of appetite
Person looks pale, feels depressed and
partially immobilized
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Advanced cases: ScurvyAdvanced cases: Scurvy
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At advanced stages:
suppurating wounds,
loss of teeth
Eventually DEATH !
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Treatment of ScurvyTreatment of Scurvy
Scurvy - treated with large amounts of vitamin C
Better taken in several amounts throughout the daybefore meals.
If taken in one large dose, not toxic but can cause
discomfort by diarrhoea Best source - vitamin supplement tablets ,
Uncooked/raw fruit cooked version usually havenutrient leached or decomposed
Liver meat products
CITRUS oranges, lime lemons juice eg as used tocure & prevent scurvy by sailors in the 1700s
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CURE
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ReferencesReferences
Cunningham JJ, Ellis SL, McVeigh KL, et al. Reduced mononuclearCunningham JJ, Ellis SL, McVeigh KL, et al. Reduced mononuclearleukocyte ascorbic acid content in adults with insulinleukocyte ascorbic acid content in adults with insulin--dependentdependentdiabetes mellitus consuming adequate dietary vitamin C.diabetes mellitus consuming adequate dietary vitamin C.MetabolismMetabolism 1991;40:1461991;40:1469.9.http://www.revital.co.uk/Health_Directory/Concern/Diabetes_Typhttp://www.revital.co.uk/Health_Directory/Concern/Diabetes_Typ
e1e1 EXTRACELLULARMATRIX,http://www.steve.gb.com/science/extracellhttp://www.steve.gb.com/science/extracell
ular_matrix.html#collagenular_matrix.html#collagen
Maxey M.A. Observation of Phagocytosis and Respiratory Burst inMaxey M.A. Observation of Phagocytosis and Respiratory Burst inNeutrophils,2006,Neutrophils,2006,http://www.aai.org/committees/education/Curriculum/2006/Marjohttp://www.aai.org/committees/education/Curriculum/2006/MarjorieMaxeyApproved.pdfrieMaxeyApproved.pdf
ReboucheRebouche C.JC.J. Ascorbic acid and. Ascorbic acid and carnitinecarnitine biosynthesis.1991,biosynthesis.1991,American journal of clinical nutrition,American journal of clinical nutrition,http://www.ncbi.nlm.nih.gov/pubmed/1962562http://www.ncbi.nlm.nih.gov/pubmed/1962562
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ReferencesReferences
Kelly G, The Interaction of Cigarette Smoking and Antioxidants. Part III:Kelly G, The Interaction of Cigarette Smoking and Antioxidants. Part III:Ascorbic Acid Alternative Medicine Review, Volume 8, Number 1, 2003 ,Ascorbic Acid Alternative Medicine Review, Volume 8, Number 1, 2003 ,http://www.thorne.com/media/smoking_antioxidants8http://www.thorne.com/media/smoking_antioxidants8--1.pdf1.pdf
HowenstineHowenstine J, 2008, Ascorbic acid competes with sugar in the immuneJ, 2008, Ascorbic acid competes with sugar in the immunesystem.system. http://lifehttp://life--
enthusiast.com/index/Articles/Howenstine/Ascorbic_Acidenthusiast.com/index/Articles/Howenstine/Ascorbic_Acid
http://www.flickr.com/photos/26387449@N05/2476929972/
ScurvyAwarenessProgram, 2006,http://www.bigdeadplace.com/scurvyawareness.html
http://www.biochemsoctrans.org/bst/031/1143/0311143.pdf
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In Summary:In Summary: Vitamin C ,DEFICIENCYVitamin C ,DEFICIENCY
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W
ithout adequate vitamin c supply-no hydroxylation of procollagen
weak organs, cartilage and bloodvessels result- maybe internalbleeding without injury.
Lack of ascorbate results in inabilityto fight infection adequately asrespiratory burst fails!!