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mucosal block theory

fe metabolism

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mucosal block theory

  1. 1. “Mucosal Block Theory” Presenter –Seema Bisht Msc . Medical Biochemistry Submitted to :- Dr. Aparna Misra
  2. 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. 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. 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. 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. 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. 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. 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. 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. 10. Factors :- 1. Source of iron has marked effect on absorption. a. Heam iron by animal product ,Hb, myoglobin (absorbs 20-30%) b. 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. 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) ,