Page 320 - Textbook of Pathology, 6th Edition

304 thus, the humans are entirely dependent upon dietary
sources. The average daily requirement for vitamin B is
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2-4 μg.
ABSORPTION. After ingestion, vitamin B in food is
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released and forms a stable complex with gastric R-binder.
R-binder is a form of glycoprotein found in various secretions
(e.g. saliva, milk, gastric juice, bile), phagocytes and plasma.
On entering the duodenum, the vitamin B -R-binder
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complex is digested releasing vitamin B which then binds
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to intrinsic factor (IF). The IF is a glycoprotein of molecular
weight 50,000 produced by the parietal cells of the stomach
and its secretion roughly parallels that of hydrochloric acid.
The vitamin B -IF complex, on reaching the distal ileum,
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binds to the specific receptors on the mucosal brush border,
thereby enabling the vitamin to be absorbed. The IF,
therefore, acts as cell-directed carrier protein similar to
transferrin. The receptor-bound vitamin B -IF complex is
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taken into the ileal mucosal cells where after several hours
the IF is destroyed, vitamin B released and is transferred Figure 12.18 Biochemical basis of megaloblastic anaemia (THF =
SECTION II
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to another transport protein, transcobalamin (TC) II. The tetrahydrofolate; DHF = dihydrofolate; PGA = pteroyl glutamic acid; dUMP
= deoxy uridylate monophosphate; dTMP = deoxy thymidylate monophos-
vitamin B -TC II complex is finally secreted into the portal phate).
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circulation from where it is taken by the liver, bone marrow
and other cells. There are 2 major vitamin B binding Lack of adenosyl B leads to large increase in the level
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proteins—TC I and TC II, and a minor protein TC III. TC I is of methyl malonyl CoA and its precursor, propionyl CoA.
not essential for vitamin B transport but functions primarily This results in synthesis of certain fatty acids which are
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as a storage protein while TC III is similar to TC II and binds incorporated into the neuronal lipids. This biochemical
a small amount of vitamin B (see Fig. 12.12,B). abnormality may contribute to the neurologic complications
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TISSUE STORES. Normally, the liver is the principal storage of vitamin B deficiency.
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site of vitamin B and stores about 2 mg of the vitamin, while
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other tissues like kidney, heart and brain together store about Folate Metabolism
2 mg. The body stores of vitamin B are adequate for 2-4
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years. Major source of loss is via bile and shedding of BIOCHEMISTRY. Folate or folic acid, a yellow compound,
intestinal epithelial cells. A major part of the excreted vitamin is a member of water-soluble B complex vitamins with the
B is reabsorbed in the ileum by the IF resulting in chemical name of pteroyl glutamic acid (PGA). Folic acid does
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enterohepatic circulation. not exist as such in nature but exists as folates in
polyglutamate form (conjugated folates). For its metabolic
FUNCTIONS. Vitamin B plays an important role in general action as co-enzyme, polyglutamates must be reduced to
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cell metabolism, particulary essential for normal dihydro- and tetrahydrofolate forms.
haematopoiesis and for maintenance of integrity of the
nervous system. Vitamin B acts as a co-enzyme for 2 main SOURCES. Folate exists in different plants, bacteria and
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biochemical reactions in the body: animal tissues. Its main dietary sources are fresh green leafy
Haematology and Lymphoreticular Tissues
Firstly, as methyl cobalamin (methyl B ) in the methylation vegetables, fruits, liver, kidney, and to a lesser extent, muscle
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of homocysteine to methionine by methyl tetrahydrofolate meats, cereals and milk. Folate is labile and is largely
destroyed by cooking and canning. Some amount of folate
(THF). The homocysteine-methionine reaction is closely synthesised by bacteria in the human large bowel is not
linked to folate metabolism (Fig. 12.18):
available to the body because its absorption takes place in
the small intestine. Thus, humans are mainly dependent
Methyl B
Homocysteine 12 Methionine upon diet for its supply. The average daily requirement is
100-200 μg.
When this reaction is impaired, folate metabolism is ABSORPTION AND TRANSPORT. Folate is normally
deranged and results in defective DNA synthesis responsible absorbed from the duodenum and upper jejunum and to a
for megaloblastic maturation. lesser extent, from the lower jejunum and ileum. However,
Secondly, as adenosyl cobalamin (adenosyl B ) in propionate absorption depends upon the form of folate in the diet.
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metabolism for the conversion of methyl malonyl co-enzyme Polyglutamate form in the foodstuffs is first cleaved by the
A to succinyl co-enzyme A: enzyme, folate conjugase, in the mucosal cells to mono- and
diglutamates which are readily assimilated. Synthetic folic
Adenosyl B 12 acid preparations in polyglutamate form are also absorbed
Propionyl CoA → Methyl malonyl CoA → Succinyl CoA as rapidly as mono- and diglutamate form because of the