vitamin c ascorbic acid
DESCRIPTION
Metabolism of Vitamin CTRANSCRIPT
VITAMIN C
Gandham. Rajeev
Department of Biochemistry,Akash Institute of Medical Sciences & Research Centre,Devanahalli, Bangalore, Karnataka, India.
E-Mail: [email protected]
Vitamin C
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)
CHEMISTRY
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
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
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
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
Metabolism
o Ascorbate 2-sulfate is urinary excretary
form of ascorbic acid
o Oxalate is another metabolite & is excreted
in urine
Excretion
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
Biochemical Functions
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
Collagen Formation
Proline
Hydroxy proline
Proline hydroxylase
Ascorbic acid (Fe++)
O2
H2O
Succinate
α- Ketoglutarate
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
Lysine hydroxylase
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
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
Parahydroxy phenyl-pyruvate hydroxylase
Parahydroxyphenyl pyruvate
Homogentisic acid
Parahydroxy phenylpyruvate
hydroxylase
Ascorbic acid (Cu ++)
O2
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 β oxidase (dopamine hydroxylase)
Dopamine
Norepinephrine
Dopamine β oxidase
Ascorbic acid
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
Iron &Heme metabolism
Protoporphyrin IX
Heme
Ferrochelatase
Ascorbic acid , Fe++
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 7 α - hydroxylase
Cholesterol
Cholesterol 7 α hydroxylase
NADPH + H+
NADP
7 α - hydroxy Cholesterol
Ascorbic acid
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
Bone formation
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
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
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
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
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
Dietary sources
RDA
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
Deficiency
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
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
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
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
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
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
Therapeutic use of vitamin C
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
Biochemical findings
References
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