mucosal block theory

fe metabolism

1. “Mucosal Block Theory” Pr e s e n ter – S e e ma B ish t M sc . M e d i c a l Bi o c h e m is t r y S u b m i t t e d to :- D r. A p a r n a M i s ra

2. Introduction Normally , the loss of iron from the body of a men is limited to 1 mg/day . Menstruating woman lose iron with menstrual blood . Around 10-20 mg of fe is taken in the diet and only about 10% is absorbed . The greatest need of iron is during infancy and adolescence . The only mechanism by which total body stores of iron is regulated is at the level of absorption . Garnick proposed a mucosal block theory for iron absorption .

3. Mucosal block theory :- Step 1 :- Soluble inorganic salts of iron are easily absorbed from small intestine . HCL present in gastric juice liberates free fe3+ from non- heam proteins . Vitamin C and glutathione in diet reduce fe3+ to fe2+ , Which is less polymerizable and more soluble form of iron . Vitamin C and amino acid can form iron –ascorbate and iron – amino acid chelates which are readily absorbed . Heam is absorbed as such.

4. Step 2:- Gastroferrin , a glycoprotein in gastric juice is believed to bind iron and facilitates its uptake in duodenum and jejunum . Step 3:- The absorption of iron from intestinal lumen into mucosal cells takes place as fe2+.

5. Step 4 :- Events in intestinal mucosal cells ( enterocyte /mucosal cell). Enterocyte in the proximal duodenum are responsible for absorption of iron . Incoming iron in the fe3+ state is reduced to fe2+ by an enzyme “ferrireductase ” present on the surface of enterocytes , it is helped by “ vitamin C” present in the foods .

6. This protein is not specific for iron as it can transport a wide rang of divalent cations. Once it is inside , it can either be stored as “feritin ” or it can be transferred across the basolateral membrane into the plasma where it is called bound to “ transferrin” . Passage of fe2+ across the basolateral membrane is carried out by another protein called iron regulatory protein 1 (IREG1) . The transfer of iron (fe2+) from the apical surfaces of enterocytes into their interiors is performed by a proton –coupled divalent metal transporter (DMT1 )

7. Most of fe2+ required to be absorbed is transferred to plasma by a fe2+ transporter ( FP) . # Fe2+ in the enterocytes also came from “heam” by the action of “ heam oxidase ” enzyme on heam . # IREG1 may interact with the copper containing protein called “hephaestin ” ,a protein similar to caeruloplasmin .hephaestin is thought to have a “ ferroxidase” activity which is important in the release of iron from cell as fe3+, the form in which, it is transported in the plasma by transferrin.

8. Overall regulation :- Iron absorption is complex and not well understood mechanistically . It is exerted at the level of the enterocyte where further absorption of iron is blocked if sufficient amount taken up ,for body need , - so called dietary regulation exerted by “mucosal block” (Garnick Hypothesis).

9. Iron requirements :- Varies according to age ,sex, weight , and state of health. Adult male –(10mg/day.) Adult female –(20 mg/day.) Pregnant woman –(10 mg/day.) Lactating woman –(25-30 mg/day). Children -10-15 mg/day.

10. Factors :- 1. Source of iron has marked effect on absorption. Heam iron by animal product ,Hb, myoglobin (absorbs 20-30%) Non heam iron –plant ,heam iron,(absorbs 1-15%). 2. Absorption of non heam iron influenced by:- compotion of diet- vit.c, glutathione, meat ,fish ,poultry . Inhibitor –phytates ,tea,oxalate,coffee, pH of the intestinal milieu –> “HCL(gastric juice) librates fe3+from non heam iron-will serve as increase solubility of dietary non heam iron” ,high alk . pH-causes precipitation . State of health .healthy adult absorbs fe -5-10%( 1-2 mg) , iron deficient –adult absorbs 10-20% ( 3-6 mg ) .

11. # Diminished absorption of gut due to :- Achlorhydria , Achyla gastrica, Resection of gut, Several Gastrectomitomies, IDA, Desquamation –less ferritin. Parasitic/bacterial/fungal infection, Malignancies , RA (rheumatoid arthritis) , PUD (PEPTIC ULCER DISEASES) ,