Page 313 - Concise Pathology for Exam Preparation ( PDFDrive )

298 SECTION II Diseases of Organ Systems

Folate

1. Dietary sources of folate: Green leafy vegetables are a rich source of folate. Moderate
amounts are present in meat, and milk is a poor source.
2. Absorption, transport and storage of folate:
(a) Folate is a yellow compound with a chemical name pteroylglutamic acid (PGA).
(b) It exists in nature as a polyglutamate (conjugated folate).
(c) For its action as a coenzyme, it must be converted to dihydro or tetrahydro form.
(d) Folate is absorbed in the proximal jejunum and ileum; the mechanism of absorp-
tion, however, is unclear.

Conjugases along the brush border
Polyglutamates Monoglutamates
• Reduction
• Methylation
Methyl FH4

(e) Folate circulates free or bound to albumin in the plasma as N5-methyl FH4.
(f) Storage in liver is in polyglutamate form.
3. Functions of folate:
(a) Folates act as 1-carbon unit carriers and are needed for synthesizing DNA and
RNA, as well as the conversion of homocysteine to methionine (Flowchart 12.5).

Thymidylate synthetase reaction
Deoxyuridylate X Deoxythymidylate
monophosphate monophosphate
(dUMP) (dTMP)

DHF
Methylene DHF reductase
THF
THF
Methionine
DNA
Methyl
group Vitamin B 12

Methyl THF Homocysteine
(plasma folate)

X–Block due to folate deficiency.
FLOWCHART 12.5. Role of B 12 and folate in DNA synthesis.

(b) Synthesis of purines
(c) Histidine metabolism (deficiency of folate leads to increased formiminoglutamic
acid or FIGLU)

Macrocytic Anaemia
Macrocytosis may be
• Megaloblastic (with impaired DNA synthesis)
• Nonmegaloblastic (with normal DNA synthesis)
Causes of Megaloblastic Macrocytosis
1. Deficiency of vitamin B 12 and/or folate
2. Resistance to B 12 or folic acid therapy due to metabolic inhibitors of DNA synthesis or
folate metabolism

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