Vitamin C :Deficiency

( Scurvy)

by M. Mandenge 1
 Vitamin C : Structure

Vitamin C
Black is carbon, red is oxygen, and white is hydrogen

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 Background

 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 glucose
to vitamin C
 Glucose for Vitamin C production in animals
extracted 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, → must
SUPPLEMENT in diet.

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 Structural forms

L-ascorbate(oxidized form) L-dehydroascorbate

 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-ascorbate
form by enzymes & glutathione so not all is lost.

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 Importance/Function:

 Antioxidant - lessen oxidative stress - alongside enzyme

glutathione peroxidase to revitalize vit. E (fat-soluble) to
stop free radical chain reactions in fluids & indirectly in
lipids.
 A substrate for ascorbate peroxidase
 Enzyme cofactor for biosynthesis
 Electron donor for eight different enzymes;
2 needed for carnitine synthesis – essential for
fatty acid transport into mitochondria for ATP
generation
cofactor for (epsilon-N-trimethyllysine hydroxylase and
gamma-butyrobetaine hydroxylase)
One modulates tyrosine metabolism
Other enzymes add amide groups to peptide
hormones, increasing stability.

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 Importance/Function:

3 involved in collagen hydroxylation;

{prolyl 4-hydroxylase,
prolyl 3-hydroxylase and
lysyl hydroxylase}
add –OH to amino acids proline & lysine in collagen
subunits allowing the collagen molecule to assume
its triple helix structure(see slide8)

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 Function

 serves as a natural aspirin, by combating inflammation

and pain- accomplishes this by inhibiting secretion of the
prostaglandins that contribute to such symptoms.
 inhibits aldose reductase - converts glucose to sorbitol -
accumulation associated with development of diabetic
complications incl. cataracts, retinopathy & neuropathy.

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 Vitamin C required for
hydroxylation

Vitamin C required to
export procollagen
out of cell

Figure . Flowchart of collagen biosynthesis 8

 Collagen Hydroxylation
Vitamin c as electron
donor

Vitamin C to export
procollagen out of
cell

Procollagen polypeptide chains made on ribosomes of rough ER and

secreted into lumen, where modified by hydroxylation of certain
proline and lysine residues and glycosylation before chain association
and triple helix formation
 Significance of collagen

 Most abundant protein in the body, collagen accounts

for more mass than all other proteins put together.
 forms connective fibres
in skin, ligaments, cartilage, bones and teeth.

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 Significance of collagen
 Acts as a kind of intracellular glue giving support,
shape and bulk to blood vessels, bones, & organs
(eg. heart, kidneys and liver).
 Its fibres keep bones & blood vessels strong, & help
to anchor our teeth to gums.
 Also required for repair of blood vessels, bruises, &
broken bones.

Collagen fibrils have a service life of ~10 years: most enzymes

turn-over in about an hour.
 Vitamin C Deficiency : Scurvy

 Recommended Daily Allowance >100mg

 Body able to store a minimum amount & if not
supplemented 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 individuals

 Babies of mothers taking high doses of vitamin C

during pregnancy
 Bottle fed babies – Vitamin C decomposed by
pasteurization (melt point 190˚ C)
 Using repetitive cooking methods
– decomposed at 190˚C
 {Elderly people,
 Alcoholics – } poor eating habits
 Factors increasing Vitamin C requirements are viral
illness & fever e.g.. INFLUENZA
-respiratory burst - level of ascorbic acid in leukocytes
may be 80x > found in plasma.

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 Respiratory Burst

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 the

hexose monophosphate (HMP)
shunt- reduces coenzyme NADP
to NADPH. Phagocytes need
NADPH to create superoxide +
other reactive oxygen species
used to destroy pathogens.

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 Most Susceptible individuals

 Diabetics – Vitamin C competes with glucose to reach

tissues & organs through a common cellular
transport system.
Insulin moves both glucose and ascorbic acid
constantly competing for insulin transport so diets high in
sugar and carbohydrates decrease amount of ascorbic
acid entering cells
Insufficient insulin supply can inhibit vitamin C
transport to cells.
 Smokers - One estimate suggests cigarette smoke
contains on the order of 1014 free radicals per inhalation.
Free radicals capable of inducing oxidative stress.

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Scurvy !!!

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 Scurvy

 Synthesized collagen is too unstable to

perform function
 Leads to formation of liver spots on skin especially
on thighs & legs
 Pain & tenderness of legs
 Exhaustion and general weakness
 Spongy gums , loose teeth & bleeding from all
mucous membranes
 Loss of appetite
 Person looks pale, feels depressed and
partially immobilized

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Advanced cases: Scurvy

At advanced stages:
suppurating wounds,
loss of teeth
Eventually DEATH !

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 Treatment of Scurvy

 Scurvy - treated with large amounts of vitamin C

 Better taken in several amounts throughout the day
before 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 have
nutrient leached or decomposed
 Liver meat products
 CITRUS – oranges, lime lemon’s juice eg as used to
cure & prevent scurvy by sailors in the 1700’s

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CURE

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 References

 Cunningham JJ, Ellis SL, McVeigh KL, et al. Reduced mononuclear

leukocyte ascorbic acid content in adults with insulin-dependent
diabetes mellitus consuming adequate dietary vitamin C.
Metabolism 1991;40:146–9.
http://www.revital.co.uk/Health_Directory/Concern/Diabetes_Typ
e1
 EXTRACELLULARMATRIX,
http://www.steve.gb.com/science/extracellular_matrix.ht
ml#collagen
 Maxey M.A. Observation of Phagocytosis and Respiratory Burst in
Neutrophils,2006,
http://www.aai.org/committees/education/Curriculum/2006/Marjo
rieMaxeyApproved.pdf
 Rebouche C.J. Ascorbic acid and carnitine biosynthesis.1991,
American journal of clinical nutrition,
http://www.ncbi.nlm.nih.gov/pubmed/1962562

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 References

 Kelly G, The Interaction of Cigarette Smoking and Antioxidants. Part III:

Ascorbic Acid Alternative Medicine Review, Volume 8, Number 1, 2003 ,
http://www.thorne.com/media/smoking_antioxidants8-1.pdf
 Howenstine J, 2008, Ascorbic acid competes with sugar in the immune
system.
http://life-enthusiast.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: Vitamin C ,DEFICIENCY

Without adequate vitamin c supply-

no hydroxylation of procollagen –
weak organs, cartilage and blood
vessels result- maybe internal
bleeding without injury.
Lack of ascorbate results in inability
to fight infection adequately as
respiratory burst fails!!

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