Page 312 - Concise Pathology for Exam Preparation ( PDFDrive )

12 Haematology 297

(b) Passive mechanism
(i) No carrier molecule involved
(ii) Seen with supraphysiological doses of vitamin B 12
(iii) Absorption occurs through the buccal, gastric and jejuna mucosa
3. Transportation of Vitamin B 12 : Cobalamin is a general term for compounds with bio-
logic vitamin B 12 activity. These compounds are involved in nucleic acid metabolism,
methyl transfer, myelin synthesis and repair. They are necessary for the formation of
normal RBCs. Cobalmin has a transport form (methylcobalamin) and a storage form
(adenosylcobalamin). There are three major vitamin B 12 -binding proteins in plasma
namely transcobalamins I, II and III.
Transcobalamin I (Haptocorrin)
• a-1 Globulin synthesized by granulocytes
• 70–80% of endogenous B 12 is bound to TC I
• Required for storage and not essential for transport; therefore, its absence does not
lead to clinical signs of B 12 deficiency
Transcobalamin II
• b-Globulin synthesized in liver
• Essential for transport of B 12 from organ to organ and from cell to cell (B 12 bound to
TC II is known as holotranscobalmin or holo-TC)
• Deficiency leads to severe megaloblastic anaemia
Transcobalamin III
• Binds a small amount of B 12
4. Storage of B 12
(a) The liver stores large amounts of vitamin B 12 followed by the kidneys, heart and brain.
(b) B 12 is excreted through bile and shedding of intestinal epithelial cells (enterohe-
patic reabsorption helps to retain vitamin B 12 ).
5. Functions of B 12
(a) Methylmalonyl CoA
• Methylmalonyl CoA mutase
• Adenosylcobalamin (B )
12
Succinyl CoA

(b) Homocysteine
FH4
Methyl group
Methylcobalamin
N5-methyl-THF
Methionine dUMP
FH4 N5, 10-methylene FH4

dTMP DNA
Absorbed N5-methyl FH4 gives away a methyl group to synthesize methionine from
homocysteine in a step requiring cobalamin and generates FH4 (tetrahydrofolate), which
is reconjugated to N5, 10-methylene FH4 for use in thymidylate and purine synthesis.
6. Deficiency of B 12 : Leads to

(a) Increased levels of methylmalonate and propionate

Synthesis of abnormal myelin lipids

Myelin degeneration and neurological abnormalities
(b) Impaired DNA synthesis and trapping of folate as methyltetrahydrofolate (FH4)

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