Iron Metabolism

Iron

Ferrous (Fe2+) and ferric (Fe3+)

Oxidative reactions

Transferrin, Ferritin, Lactoferrin

In the heme moiety of erythrocytes (haemoglobin)

Liver, meat, egg yolk, green leafy vegetables and whole grain cereals

Heme iron

3-4 g

20-25%

To hold iron for functional activity or for its storage and transport

To transport oxygen

Heme iron

Liver and spleen

Transferrin

Myoglobin

Ferritin

Iron deficiency anemia

Iron overload

All of the above

It produces ATP

Vitamin C

Transferrin transports iron to the cells

Ferritin

Carrying oxygen from the lungs to the tissues

Storing oxygen in muscle cells

Fatigue, weakness, and shortness of breath

Damage to the liver, heart, and other organs

Iron deficiency anemia

Iron binds to the proteins to enable oxygen transport

Liver and heart

Heme iron

All of the above

Vegetarians

All of the above

Iron deficiency anemia

Transporting iron throughout the body

Storing iron in muscle cells

Liver

4 g

Through sloughing of tissues

Iron deficiency anemia

Increased demand for iron

Excessive iron absorption

Therapeutic phlebotomy

Duodenum

Dcytb

DMT1

Ascorbic acid

Ferritin

Serum ferritin

20-30%

Desferrioxamine

Saturation of serum transferrin

Pathogenic microorganisms

Vibrio vulnificus

Death within 24 hours

Serum transferrin

Ferritin

Vibrio vulnificus

Rapidly progressive infection

Iron Deficiency and Iron Overload

Increased demand for iron, increased loss of iron, nutritional deficiency, inability to absorb iron, damage to the intestinal lining, and inflammation

Microcytic and hypochromic red blood cells, low hemoglobin levels, and low serum ferritin values

Examination for the cause and source of bleeding, iron supplementation, and transfusion with packed red blood cells if the deficiency is severe

Genetic mutations, secondary factors such as blood transfusions or overdosing on iron pills or injections

Cirrhosis and liver tumors, diabetes mellitus, and cardiac failure

Dietary changes, therapeutic phlebotomy (periodic withdrawals of large amounts of blood), and avoiding iron supplements, iron-rich foods, alcohol, and raw or undercooked fish and shellfish.

Liver, meat, egg yolk, green leafy vegetables, and whole grain cereals.

Key role in synthesis of oxygen transporting and oxygen storage proteins. Formation of heme enzymes and other iron-containing enzymes involved in electron transfer and oxidation-reductions. DNA synthesis and repair.

Heme iron is found in animal sources like meat, fish, and poultry, and is easily absorbed (high bioavailability). Non-heme iron is found in plant sources like dried beans, peas, fruits, and vegetables, and has relatively lower bioavailability.

Vegetarians.

Key role in synthesis of oxygen transporting and oxygen storage proteins. Formation of heme enzymes and other iron-containing enzymes involved in electron transfer and oxidation-reductions. DNA synthesis and repair.

Heme iron is responsible for synthesis of oxygen transporting and oxygen storage proteins.

Non-heme iron is involved in electron transfer and oxidation-reductions, as well as DNA synthesis and repair.

To eliminate excess iron from the body

Desferrioxamine

Transferrin can be close to saturation, making small amounts of free serum iron available

When an individual is overloaded with iron

Vibrio vulnificus

Death within 24 hours

Via urine

Iron supplementation

Meat, fish, poultry

The small intestine (largest amount absorbed in the duodenum by enterocytes of the duodenal lining)

The free ion (ferrous form) or as heme iron (iron is split off from the porphyrin ring in the mucosal cytoplasm)

Ferric reductase enzyme on the enterocytes’ brush border, duodenal cytochrome B (Dcytb)

Divalent metal transporter 1 (DMT1)

Ascorbic acid, HCl, iron deficiency

Phytates (storage form of phosphates - abundant in cereals), tannins and other polyphenol compounds in fruits, tea coffee, red wine cocoa, achlorhydra GI disease, antacids, iron overload, gastric bypass surgery

Ferritin

Ferroportin

True

True

True

True

False

True

True

True

False

True

True

False

True

False

True

True

True

True

True

True

True

True

True

True

True

True

True

True

True

True

Heme iron = Easily absorbed (high bioavailability) Non-heme iron = Relatively lower bioavailability

Liver, meat, egg yolk, green leafy vegetables and whole grains cereals = Dietary Meat, fish and poultry = Animal sources Dried beans, peas fruits and vegetables = Plant sources

Synthesis of oxygen transporting and oxygen storage proteins = Key role in oxygen transportation Formation of heme enzymes and other iron-containing enzymes = Involved in electron transfer and oxidation-reductions DNA synthesis and repair = Important for genetic processes

Iron deficiency = Condition characterized by a lack of iron in the body Heme iron = Iron from animal sources which is easily absorbed Ferritin = Protein responsible for storing iron when it is not immediately needed Transferrin = Protein responsible for transporting iron throughout the body

Iron overload = Can lead to cirrhosis and liver tumors Iron deficiency anemia = Caused by insufficient iron levels in the body Vibrio vulnificus infection in iron overloaded individuals = Can be rapidly progressive with high mortality

Iron from animal sources is more easily absorbed than iron from plant sources = True Most of the iron in the body is contained in hemoglobin = True Hephaestin is a ferroxidase found mainly in the small intestine = True Heme iron is found in plant sources like dried beans and peas = False

Ferroportin = Only known iron exporter in mammals Hephaestin = Ferroxidase that oxidizes Fe2+ to Fe3+ Cytochrome P450 = Reduces ferric iron (Fe3+) to ferrous iron (Fe2+) in the small intestine

Iron Absorption = Major site of absorption is the small intestine Iron Transport = The protein involved in the transport of iron is transferrin Iron Storage = The major protein involved in the storage of iron is ferritin Iron Overload = Saturation above 50% of transferrin is indicative of this condition

Ascorbic acid = Increases iron absorption Phytates = Inhibits iron absorption Tannins = Inhibits iron absorption Iron deficiency = Increases synthesis of DMT1, Dcytb, and ferroportin

Dcytb = Reduces ferric iron (Fe3+) to ferrous (Fe2+) DMT1 = Transports iron across the enterocyte’s cell membrane Ferroportin = The only known iron exporter in mammals Hephaestin = Oxidizes Fe2+ to Fe3+

Ferric Iron = Reduced to ferrous iron in the small intestine Heme Iron = Iron is split off from the porphyrin ring in the mucosal cytoplasm Non-Heme Iron = Inhibited by phytates and polyphenol compounds Transferrin-Bound Iron = Delivered mainly to bone marrow and liver

Iron Deficiency = Increases transferrin synthesis Inflammation = Less iron is absorbed to deprive bacteria of iron Achlorhydra = Causes decreased absorption of iron Liver Disease = May lead to increased transferrin saturation

Transferrin = Involved in the transport of iron in the blood Ferritin = The major protein involved in the storage of iron Hephaestin = Can oxidize Fe2+ to Fe3+ Apoferritin = Regulates iron absorption in response to the body’s needs

Ferric Iron = Reduced to ferrous iron in the small intestine Heme Iron = Iron is split off from the porphyrin ring in the mucosal cytoplasm Non-Heme Iron = Inhibited by phytates and polyphenol compounds Transferrin-Bound Iron = Delivered mainly to bone marrow and liver

Desferrioxamine = Forms a complex with iron and is eliminated via urine Transferrin = Binds iron for transport Ferritin = Stores iron when it is not immediately needed Hephaestin = Ferroxidase found mainly in the small intestine

Iron overload = Serum transferrin value can be close to saturation, making small amounts of free serum iron available Iron deficiency = Lack of iron in the body Thalassemias = Bleeding is not an option Vibrio vulnificus infection in iron overloaded individuals = Rapidly progressive infection, with death ensuing within 24 h after ingestion of the meal

Vibrio vulnificus = Marine bacteria, found in a small percentage of oysters and commercial shellfish Nonpathogenic microorganisms = Iron dependent and cannot compete against partially saturated transferrin in the normal individual Pathogenic microorganisms in iron overloaded individuals = Usually nonpathogenic microorganisms that can now become pathogenic due to iron overload Microorganisms in normal individuals = Entirely free of symptoms after consuming the same food as iron overloaded individuals

Iron chelating therapy = Use of Desferrioxamine to eliminate excess iron from the body Iron overload = Condition characterized by an excess of iron in the body Ferrioxamine = Complex formed between Desferrioxamine and iron Thalassemias = Conditions where bleeding is not an option

Iron absorption = Enhanced by factors such as vitamin C and acidic environment Iron excretion = Occurs via urine in iron chelating therapy Iron storage = Role of ferritin when iron is not immediately needed Iron transport = Role of transferrin

Iron overload = Rapidly progressive infection with Vibrio vulnificus after ingestion of contaminated food Iron deficiency = Anemia Thalassemias = Complications arising when bleeding is not an option Infection in normal individuals = Entirely free of symptoms after consuming the same food as iron overloaded individuals

Transferrin = Binds iron for transport Ferritin = Stores iron when it is not immediately needed Hephaestin = Ferroxidase found mainly in the small intestine Desferrioxamine = Forms a complex with iron for elimination

Iron overload = No specific symptoms, but may lead to complications like infection Iron deficiency = Fatigue, weakness, shortness of breath Thalassemias = Complications when bleeding is not an option Vibrio vulnificus infection in iron overloaded individuals = Rapidly progressive infection, with death ensuing within 24 h after ingestion of the meal

Rapidly progressive infection = Iron overload with Vibrio vulnificus infection Anemia = Iron deficiency Nonpathogenic microorganisms becoming pathogenic = Iron overload Lack of energy = Thalassemias

Iron Deficiency Anemia = Hemoglobin < 13 g/dl (male), 12 g/dl (female) Iron Overload = Iron content of the body can be elevated to values as high as 100 g in patients due to excessive absorption Iron Deficiency = The serum transferrin value (expressed as the total iron binding capacity) will be elevated with a serum iron saturation of less than 16 % Normal Iron Level = A loss of about 1 mg day–1 occurs in a healthy adult

Iron Deficiency = Inability to absorb iron (use of acid reducing medications like proton pump inhibitors) Iron Overload = Overdosing on iron pills or injections

Iron Deficiency = Management: a careful examination for the cause and source of bleeding Iron Overload = Therapeutic phlebotomy: Periodic withdrawals of large amounts of blood, where the iron is contained in the hemoglobin

Iron Deficiency Anemia = Microscopic examination of blood shows characteristic microcytic (small in size) and hypochromic (under-pigmented) RBCs Iron Overload = The accumulation of iron in the liver, pancreas, and heart can lead to cirrhosis and liver tumors, diabetes mellitus, and cardiac failure respectively Iron Deficiency = Damage to the intestinal lining. (surgery involving the duodenum, which severely reduce the surface area available for absorption)

Iron Deficiency = Functional or actual iron deficiency may be caused by Increased demand for iron, which the diet cannot accommodate Iron Overload = Iron overload also referred to as Hemochromatosis may be caused by; Genetic mutation (HFE gene) – associated with a marked inappropriate increase in iron absorption

Iron Deficiency Anemia = The liver produces more transferrin, presumably attempting to maximize use of the little iron that is available (thereby increasing overall binding capacity) Iron Overload = Often used to describe hemochromatosis because it can lead to darkening of the skin and hyperglycemia Iron Deficiency = Microscopic examination of blood shows characteristic microcytic (small in size) and hypochromic (under-pigmented) RBCs

Iron Deficiency Anemia = Bone marrow aspiration will reveal no storage iron to be present and serum ferritin values are virtually zero Iron Overload = Iron content of the body can be elevated to values as high as 100 g in patients due to excessive absorption Iron Deficiency = The serum transferrin value (expressed as the total iron binding capacity) will be elevated with a serum iron saturation of less than 16 % Normal Iron Level = A loss of about 1 mg day–1 occurs in a healthy adult