[MCQs] Megaloblastic Anemias – Part 1

All forms of Cobalamin (vit. B12) have a cobalt atom at the center of corrin ring

Cobalamin (vitamin B12) exists in a number of different chemical forms. Methylcobalamin is the form of cobalamin in human plasma & in cell cytoplasm.

Methylcobalamin is the cofactor for methionine synthase.

Cobalamin is a complex organometallic compound in which a “cobalt” atom is situated within a corrin ring. It cannot be synthesized in human body & must be supplied in diet of animal products (meat, fish, and dairy products). Daily requirement for cobalamin is ~ 1 - 3 µg.

Body stores of 2 - 3 mg are sufficient for 3 - 4 years if supplies are completely cut off essentially due to enterohepatic cycle & size of liver stores. There is a permanent liver reserve of 1 mg.

Dietary intake of cobalamin is more than adequate for body’s requirements, except in complete vegetarians & their breast-fed infants. Deficiency of cobalamin is almost always due to malabsorption

Cobalamin absorption can be passive through buccal, duodenal & ileal mucosa. More efficient normal physiologic active mechanism is through ileum mediated by gastric intrinsic factor (IF)

Dietary cobalamin combines rapidly with a salivary glycoprotein that belongs to the family of cobalamin-binding proteins known as haptocorrins (HCs)

In intestine, haptocorrin is digested by pancreatic trypsin to release cobalamin which is transferred to IF

IF is produced in the acid-secreting gastric parietal cells located in oxyntic gland of fundus & body of stomach. Its secretion parallels that of hydrochloric acid

Cubilin is a specific receptor on microvillus membrane of enterocytes. IF-cobalamin attaches to it and enters the ileal cell, where IF is destroyed..

Cubulin acts through amnionless (AMN), an endocytic receptor protein that directs sublocalization and endocytosis of cubulin with its ligand IF-cobalamin complex.

Cubilin also is present in yolk sac and renal proximal tubular epithelium.

Cobalamin in food is released and forms a stable complex with gastric R binder that is found in secretions like saliva, milk, gastric juice and bile.

On entering the duodenum, the cobalamin-R binder complex is digested, releasing the cobalamin, which then binds to intrinsic factor (IF), a 50-kDa glycoprotein which catalyzes the conversion of homocysteine to methionine.

TC I is derived from specific granules in neutrophils. Normally, it is ~ two-thirds saturated with cobalamin, which it binds tightly. TC I does not enhance cobalamin entry into tissues.

Two main cobalamin transport proteins in human plasma are TC I & TC II. TC II carries cobalamin in plasma & gives up cobalamin to marrow, placenta, and other tissues.

Folic acid is the common name for pteroylmonoglutamic acid.

Fruits and vegetables are the primary dietary source of folic acid. Folate concentrations is highest in liver, yeast, spinach, other greens, and nuts.

Daily requirement is normally about 100 pg, but this may be increased several fold during periods of enhanced metabolic demand such as pregnancy, infancy, malignancy, increased hematopoiesis (chronic hemolytic anemias), chronic exfoliative skin disorders, hemodialysis.

Total-body folate in adult is ~10 mg. Daily adult requirement is ~100 pg, so stores are sufficient for 3 - 4 months, if severe folate deficiency develops rapidly

Folates in food are largely conjugated to a chain of glutamic acid residues which impair its intestinal absorption. Conjugases (y-glutamyl carboxypeptidases) in gut lumen convert polyglutamates to mono- & diglutamates, which are readily absorbed in proximal jejunum.

Plasma folate is primarily in the form of N5-methyltetrahydrofolate. All dietary folates are converted to 5-methyl THF (5-MTHF) within small-intestinal mucosa before entering portal plasma.

N5-methyltetrahydrofolate is a monoglutamate