Metabolism of Vitamin C

1. VITAMIN C
Gandham. Rajeev
Department of Biochemistry,
Akash Institute of Medical Sciences
& Research Centre,
Devanahalli, Bangalore,
Karnataka, India.
E-Mail: gandhamrajeev33@gmail.com

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

5. o The acidic property of vitamin C is due to the
enolic hydroxyl group
o Vitamin C is strong reducing agent
o L – ascorbic acid undergoes oxidation to form
dehydro ascorbic acid & it is reversible reaction
o Ascorbic acid & dehydro ascorbic acid are
biologically active
o D – ascorbic acid is biologically inactive

6. o Ascorbic acid is present in all tissue & plasma as
reduced form
o The ratio of ascorbic acid to dehydro ascorbic acid
in many tissues is 15:1
o On dehydration, dehydroascorbic acid is
irreversibly converted to 2,3 – diketogulonic acid
which is inactive
o Oxidation of ascorbic acid is rapid in the presence
of copper

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

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

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

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

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

13. Proline
Hydroxy proline
Proline hydroxylase
Ascorbic acid
(Fe++)
O2
H2O
Succinate
α- Ketoglutarate

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

15. o Hydroxylation occurs after the peptide chain synthesis (post-
translational modifications)
o In vitamin C deficiency, collagen synthesis is defective,delayed
wound healing
o It is administered after surgery to enhance wound
healing
Lysine
Hydroxy lysine
Lysine hydroxylase
Ascorbic acid
(Fe++)
O2
H2O
Succinate
α- Ketoglutarate

16. o In tyrosine catabolism Parahydroxy phenyl-
pyruvate hydroxylase catalyzes the formation of
homogentisic acid form parahydroxy phenyl
pyruvate
o Ascorbic acid is required for this reaction
Parahydroxyphenyl pyruvate
Homogentisic acid
Parahydroxy phenylpyruvate
hydroxylase
Ascorbic acid
(Cu ++)
O2

17. o In catecholamine synthesis Dopamine β oxidase
catalyzes the formation of norepinephrine from
dopamine
o This is essential for synthesis of catecholamines
o Adrenal medulla is rich in vitamin C
Dopamine
Norepinephrine
Dopamine β oxidaseAscorbic acid

18. o Ferrochelatase catalyzes the formation of heme
from protoporphyrin IX
o Vitamin C is necessary for the incorporation of
Fe++ into protoporphyrin IX to form heme
o Vitamin C keeps the iron in ferrous form
Protoporphyrin IX
Heme
FerrochelataseAscorbic acid , Fe++

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

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

21. o Iron metabolism:
o Ascorbic acid increases the iron absorption from
the intestine
o Ascorbic acid reduces ferric iron to ferrous state,
which is commonly absorbed
o Folic acid metabolism:
o Vitamin C needed for the formation of FH4
o In association with FH4, it is involved in
maturation of RBC

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

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

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

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

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

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

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

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

32. o Without the normal ground substance, the
deposition of bone is arrested
o The bones become weak and fractures easily
o Hemorrhage into joint cavities
o Painful swelling of joints may prevent locomotion
of the patient
o Vitamin C & vitamin B are essential nutrients to
maintain bone density & bone quality

33. o Anemia
o 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
o Fatigue, depression, & susceptibility to
infections are associated with vitamin C
deficiency

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

36. o Decreased plasma, platelet and leukocyte
ascorbic acid levels
o Impaired vitamin C saturation test
o The test involves the measurement of urinary
ascorbic acid after a test dose of vitamin C
o In vitamin C deficiency, urinary excretion of
ascorbic acid is decreased after a test dose of
vitamin C

38.  Harper’s Biochemistry 25th 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