Vit CDeficiency++

8/9/2019 Vit CDeficiency++

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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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2020

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!!

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Vit CDeficiency++