Author: Ms Christa Maria Joel Moderator- Dr. Ashima Amin Department of Pathology 2nd Year MBBS (2014-2015) Father Muller Medical College

1. CHRISTA MARIA JOEL
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2. Objectives
Vitamin B12 metabolism-
Biochemistry, sources, absorption, transport and
storage, functions and vitamin B12 deficiency.
Folate metabolism-
Biochemistry, sources, absorption and transport,
tissue stores, functions and folate deficiency.
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3. Vitamin B12
 Biochemistry- complex
compound - cobalamin. Daily
requirement - 2 to 3 μg.
Therapeutic vitamin B12
preparation -
cyanocobalamine.
 Sources- animal proteins such
as kidney, liver, meat, fish,
eggs, cheese & milk.
Synthesized in human large
bowel by microorganisms but
is not absorbed from this site.
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4. Absorption,
Transport And
Storage
Vitamin B12 in food
is usually in
coenzyme form (as
deoxyadenosylcobal
amine and
methylcobalamine)
and bound to
proteins in diet.
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5. Tissue Stores
 Liver is the principal storage site of vitamin B12 and stores
about 2mg of the vitamin.
 Other tissues like kidney, heart and brain together store
about 2mg.
 Body stores of vitamin B12 are adequate for 2-4 years.
 Major source of loss is via bile and shedding of intestinal
epithelial cells.
 Major part of the excreted vitamin is reabsorbed in the
ileum by the intrinsic factor resulting in enterohepatic
circulation.
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6. Functions Of Vitamin B12
 Methylcobalamine - main form of vitamin B12 and is essential for
conversion of homocysteine to methionine and formation of
tetrahydrofolate (THF) from methyl THF.
 In vitamin B12 deficiency the main cause of impaired DNA synthesis is that
methyl THF is not converted into THF. Methyl THF accumulates in the cell
and is known as methyl THF trap.
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8.  Vitamin B12 is also required for conversion of methylmalonyl CoA to succinyl
malonyl CoA.
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9. Vitamin B12 Deficiency
 In Western countries this deficiency is most commonly due
to pernicious anaemia.
 True vegetarians and breast fed infants have dietary lack of
this vitamin.
 Gastrectomy by lack of intrinsic factor and small intestinal
lesions involving distal ileum where absorption of vitamin B12
may cause deficiency of the vitamin.
 This deficiency takes at least 2 years to develop when the
body stores are totally depleted.
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10. Folic Acid
 Biochemistry:
Folic acid or folate, a yellow compound
is a member of water soluble B complex
vitamins with the chemical name of
pteryol glutamic acid.
Does not exist as such in nature but as
folates in polyglutamate form.
For its metabolic actions, polyglutamate
must be reduced to dihydro and
tetrahydrofolate forms.
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11. Sources Of Folic Acid
 Folate exist in different plants, bacteria and animal tissues.
 Main dietary sources - fresh green leafy vegetables, fruits, liver,
kidney and to a lesser extent, muscle meats, cereals and milk.
 Folate is labile and is largely destroyed by cooking and canning.
 Some amount of folate synthesized by bacteria in the human
large bowel is not available to the body because its absorption
takes place in the intestine.
 Average daily requirement - 100-200μg.
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12. Absorption And
Transport
 Folate is normally absorbed
from the duodenum and
upper jejunum and to a
lesser extent, from the lower
jejunum and ileum.
 However the absorption
depends upon the folate in
the diet.
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13. Tissue Stores
 The liver and red cells are the main storage sites of
folate largely as methyl THF polyglutamate form.
 Total body stores of folate are about 10-12 mg
enough for about 4 months.
 Folate is lost from sweat, saliva, urine and faeces.
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14. Functions Of Folic Acid
 The active form of folic acid is THF which is the biologic
‘middleman’ involved in metabolic processes which synthesise
DNA. The various reactions in which folic acid plays a main role
are:
 Synthesis of purines required for DNA and RNA.
 Conversion of homocysteine to methionine, a reaction also
requiring vitamin B12.
 Conversion of dUMP to dTMP: 5,10- methylene THF
polyglutamate is required for conversion of d UMP to dTMP and
DNA, a rate limiting step in pyrimidine synthesis.
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15.  Metabolism of histidine: histidine is metabolized to
formiminoglutamic acid (FIGLU) which combines with THF to form
glutamic acid.
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16. Deficiency Of Folic Acid
Deficiency is due to poor dietary intake.
Other causes include malabsorption, excess folate
utilization such as in pregnancy and in various
disease states, chronic alcoholism, and excess urinary
folate loss.
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17. Clinical Features Of Vitamin B12 Deficiency And
Folic Acid Deficiency
 Anaemia- macrocytic megaloblastic anaemia is the cardinal
feature. Onset is insidious and gradually progressive.
 Glossitis- patient has a smooth, beefy, red tongue.
 Neurologic manifestations- vitamin B12 is associated with
neurological manifestations in the form of subacute combined,
degeneration of spinal cord and peripheral neuropathy while
folate deficiency develop only neuropathy
 Others- mild jaundice, angular stomatitis, purpura, melanin
pigmentation, weight loss and anorexia.
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