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- 1. IRON METABOLISM PRESENTED BY– BIKASH PATGIRI, 1ST YEAR MBBS , LAKHIMPUR MEDICAL COLLEGE, ASSAM
- 2. Contents 1. Distribution ofiron in our body 2. Biochemical function 3. Sources of iron 4. Absorption, transport and storage of iron 5. Factors affecting absorption of iron 6. Excretion of iron 7. Iron metabolism 8. Disease states
- 3. Distribution of ironin our body The total content of iron in an adult body is 3-5 g. About 70% of this occurs in the erythrocytes of blood as a constituent of hemoglobin. At least 5% of body iron is present in myoglobin of muscle. Heme is the most predominant iron-containing substance. It is a constituent of several proteins/enzymes (hemoproteins)—hemoglobin, myoglobin, cytochromes, xanthine oxidase, catalase, tryptophan pyrrolase, peroxidase. Certain other proteins contain non-heme iron e.g. transferrin, ferritin, hemosiderin.
- 5. Biochemical functions ofiron 1. Iron mainly exerts its functions through the compounds in which it is present. Hemoglobin and myoglobin are required for the transport of O 2 and CO 2. 2. Cytochromes and certain non-heme proteins are necessary for electron transport chain and oxidative phosphorylation. 3. Peroxidase, the lysosomal enzyme, is required for phagocytosis and killing of bacteria by neutrophils. 4. Iron is associated with effective immuno-competence of the body.
- 6. Sources of iron Rich sources — Organ meats (liver, heart, kidney). Good sources — Leafy vegetables, pulses, cereals, fish, apples, dried fruits, molasses. Poor sources — Milk, wheat, polished rice.
- 7. Iron ismainly absorbed in the stomach and duodenum. In normal people, about 10% of dietary iron is usually absorbed. However, in iron deficient (anemic) individuals and growing children, a much higher proportion of dietary iron is absorbed to meet the increased body demands. Iron is mostly found in the foods in ferric form (Fe3+ ), bound to proteins or organic acids. In the acid medium provided by gastric HCl, the Fe3+ is released from foods. Reducing substances such as ascorbic acid (vitamin C) and cysteine convert ferric iron (Fe3+ ) to ferrous form (Fe2+ ). Iron in the ferrous form is soluble and readily absorbed. Absorption, transport and storage of iron
- 9. 1. Acidity,ascorbic acid, alcohol, fructose and cysteine promote iron absorption. 2. In iron deficiency anemia, Fe absorption is increased to 2-10 times that of normal. 3. Small peptides and amino acids favour iron uptake. 4. Phytate (found in cereals) and oxalate (found in leafy vegetables) interfere with Fe absorption. 5. A diet with high phosphate content decreases Fe absorption while low phosphate promotes. 6. Impaired absorption of iron is observed in mal-absorption syndromes such as steatorrhea. 7. In patients with partial or total surgical removal of stomach and/or intestine, iron absorption is severely impaired. Factors affecting absorption of iron
- 10. Iron in themucosal cells : The iron (Fe 2+ ) entering the mucosal cells by absorption is oxidized to ferric form (Fe3+ ) by the enzyme ferroxidase. Fe 3+ then combines with apoferritin to form ferritin which is the temporary storage form of iron. From the mucosal cells, iron may enter the blood stream (which mainly depends on the body needs) or lost when the cells are desquamated.
- 11. Transport of Fein the plasma : The iron liberated from the ferritin of mucosal cells enters the plasma in ferrous state. Here, it is oxidized to ferric form by a copper-containing protein, ceruloplasmin which possesses ferroxidase activity. Another cuproprotein ferroxidase II also helps for the conversion of Fe2+ to Fe 3+.Ferric iron then binds with a specific iron-binding protein, namely transferrin or siderophilin (a glycoprotein with mol. wt.90,000). Each transferrin molecule can bind with two atoms of ferric iron (Fe 3+ ). The plasma transferrin (concentration 250 mg/dl) can bind with 400 mg of iron/dl plasma. This is known as total iron binding capacity (TIBC) of plasma.
- 12. Storage of iron: Iron is stored in liver, spleen and bone marrow in the form of ferritin. In the mucosal cells, ferritin is the temporary storage form of iron. A molecule of apoferritin (mol. wt. 500,000) can combine with 4,000 atoms of iron. The maximum iron content of ferritin on weight basis is around 25%. Hemosiderin is another iron storage protein which can hold about 35% of iron by weight. Hemosiderin accumulates in the body (spleen, liver) when the supply of iron is in excess of body demands.
- 13. Excretion of iron Iron is a one-way element. That is, very little of it is excreted. Any type of bleeding will cause loss of iron from the body. Menstrual flow is the major cause for loss of iron in women. Women up to menopause will lose iron at a rate about 1mg/day. The loss in male is less than 0.5ms/day. Almost no iron is excreted through urine. Feces contain unabsorbed iron as well as iron trapped in the intestinal cells, which are then desquamated. About 30% of cells in the intestinal lining is replenished everyday, and so this loss is considerable. All the cells in skin contain iron. The upper layer of skin cells are constantly being lost, and this is another route for iron loss from the body.
- 14. Iron is aone way substance Iron metabolism is unique as it operates in a closed system. It is very efficiently utilized and reutilized by the body. Further, iron losses from the body are minimal (< 1 mg/day) which may occur through bile, sweat, hair loss etc. Iron is not excreted into urine. Thus, iron differs from the vitamins or other organic and inorganic substances which are either inactivated or excreted during the course of metabolic function. Hence, iron is appropriately regarded as a one-way substance. Iron entry into the body is controlled at the absorption level, depending on the body needs. Thus the periodical blood loss in menstruating women increases its requirements. Increased iron demands are also observed in pregnancy, lactation, and in growing children.
- 15. Iron metabolism A generaloverview of iron metabolism is depicted in Fig. It shows the distribution of iron in the body and its efficient reutilization. It may be noted that 1-2 mg of iron is absorbed per day to replace the loss.
- 16. Disease states a. Thisis the most prevalent nutritional disorder worldover, including the well developed countries (e.g. USA). b. Several factors may contribute to iron deficiency anemia. c. These include inadequate intake or defective absorption of iron, chronic blood loss, repeated pregnancies and hookworm infections. d. Strict vegetarians are more prone for iron deficieny anemia. This is due to the presence of inhibitors of iron absorption in the vegetarian foods, besides the relatively low content of iron. e. Iron deficiency anemia mostly occurs in growing children, adolescent girls, pregnant and lactating women. f. It is characterized by microcytic hypochromic anemia with reduced blood hemoglobin levels (<12 g/dl). The other manifestations include apathy (dull and inactive), sluggish metabolic activities, retarded growth and loss of appetite. Treatment : Iron deficiency is treated by supplementation of iron along with folic acid and vitamin C. 1. Iron deficiency anemia
- 17. 2. Hemosiderosis a. Thisis a less common disorder and is due to excessive iron in the body. b. It is commonly observed in subjects receiving repeated blood transfusions over the years, e.g. patients of hemolytic anemia, hemophilia. c. As already stated, iron is a one-way compound, once it enters the body, it cannot escape. d. Excessive iron is deposited as ferritin and hemosiderin. e. Hemosiderosis is commonly observed among the Bantu tribe in South Africa. This is attributed to a high intake of iron from their staple diet corn and their habit of cooking foods in iron pots.
- 18. 3. Hemochromatosis a. Thisis a rare disease in which iron is directly deposited in the tissues (liver, spleen, pancreas and skin). b. Hemosiderosis is sometimes accompanied by hemochromatosis. c. Bronzed-pigmentation of the skin, cirrhosis of liver, pancreatic fibrosis are the manifestations of this disorder. d. Hemochromatosis causes a condition known as bronze diabetes
- 19. Dietary intake ofiron Adult man — 10 mg/day Menstruating woman — 18 mg/day Pregnant and lactating woman — 40 mg/day
- 20. Summary The totalcontent of iron in an adult body is 3-5 g. About 70% of this occurs in the erythrocytes of blood as a constituent of hemoglobin. Heme is the most predominant iron-containing substance. It is a constituent of several proteins/enzymes. Iron is mainly absorbed in the stomach and duodenum. In normal people, about 10% of dietary iron is usually absorbed. Iron in the ferrous form is soluble and readily absorbed. There are several factors which may interfere with the absorption of iron. Iron in plasma is transferred by Transferrin molecules. ). Each transferrin molecule can bind with two atoms of ferric iron (Fe 3+ ). The plasma transferrin (concentration 250 mg/dl) can bind with 400 mg of iron/dl plasma. This is known as total iron binding capacity (TIBC) of plasma. Iron is stored in liver, spleen and bone marrow in the form of ferritin (a temporary storage molecule). Hemosiderin is another iron storage protein. Iron metabolism is one way pathway. Some disease states are – 1. Iron deficiency anemia 2. Hemosiderosis 3. Hemochromatosis Dietary intake may vary with age and gender of an individual.
- 21. References Class notes Biochemistry by MD Rafi Satyanarayan’s Biochemistry Internet sources