COMPONENTS OF IRON IN THE BODY
Iron is a vital element that is needed by the body for oxygen transport, oxidative metabolism, and cell growth and proliferation.
Iron consumed from food will be absorbed in the duodenum and to a lesser extent in the jejunum. About 5 to 15% will be absorbed in the form of Fe2+. In the intestine Fe2+ is oxidized to Fe3+, then Fe3+ binds to apoferritin which is then transformed into ferritin and stored in the form of ferritin. Some more Fe2+ is released into the blood plasma. In the plasma Fe2+ is oxidized to Fe3+ and binds to transferrin. Transferrin transports Fe2+ into the bone marrow to combine to form hemoglobin. Transferrin transports Fe2+ to iron stores in the liver, bone marrow, spleen, and RES organs. Then it is oxidized to Fe3+. This Fe3+ combines with apoferritin to form ferritin which is then stored, the iron contained in plasma is balanced with the stored form.
Components of iron in the body
The iron component in the body consists of 3 forms of compounds, namely functional compounds in metabolism and enzymatic in the form of hemoglobin, myoglobin, enzymes, iron reserves in the form of ferritin and hemosiderin, and transport compounds in transferrin.
Iron in hemoglobin
Most of the iron is bound in hemoglobin, which is about 65-80%, which functions to transport oxygen for metabolic purposes in tissues. Hemoglobin is a metalloprotein consisting of globin, apoprotein, and 4 heme groups. The globin chain consists of 4 linked to each other. Tetramer consists of two pairs of different polypeptide subunits namely , , , . Each sub unit has a molecular weight of approximately 16,000 Daltons. At the center of the molecule there is a heterocyclic ring known as a porphyrin that binds an iron atom which is the oxygen binding site. Overall hemoglobin has a capacity of four oxygen molecules. Hemoglobin liberates O2 to the tissues and transports CO2 and protons to the lungs.1,3
Iron in myoglobin
Myoglobin is an oxygen-carrying protein found in muscle, where myoglobin acts as an oxygen reservoir and facilitates the diffusion of oxygen through cells. Myoglobin has 2 molecular components, a single polypeptide chain containing 153 amino acid residues with a molecular weight of 17,600, and a heme group, which contains iron. The heme of myoglobin is known as a prosthetic group because it is a non-protein organic molecule that is closely related to a polypeptide. The binding of the iron atom to a heme involves the four nitrogens of the pyrrole ring. The bound iron can form two additional bonds, one on each side of the heme plane, called the fifth and sixth coordination positions. At the sixth coordination position, ferrous iron in myoglobin binds one oxygen molecule. 3.4
There is 3.5% iron bound to myoglobin. Found in high concentrations in bone and heart muscle. The folding of the globin chain forms a gap that is almost filled with the heme group. Fe2+ has a high affinity for oxygen and is oxidized unidirectionally to form Fe3+. Fe3+ cannot bind oxygen. the non-covalent interaction between the amino acid site and the non-polar porphyrin ring containing the oxygen-binding site increases the affinity of Fe2+ for O2. The increased affinity protects Fe2+ from oxidation and allows reversible O2 binding. All of the amino acids that interact with nonpolar heme except for two histidines, bind directly to the iron atom of the heme and the other histidine stabilizes the oxygen binding site. In high O2 conditions, myoglobin binds a lot of O2 but in low O2 conditions, myoglobin releases O2 which is used in muscle mitochondria to produce ATP aerobically.
Iron transported in transferrin
Transferrin is a B1 globulin which is a glycoprotein with a molecular weight of 80,000 – 90,000 daltons, consisting of a single-chain polypeptide with 679 amino acids in two homologous domains. The N-terminal and C-terminal each have one binding site for Fe3+. One transferrin molecule binds 2 Fe3+ atoms. Transferrin will bind to the transferrin receptor. Each transferrin receptor binds to 2 transferrin molecules
Transferrin is mainly synthesized by liver parenchyma cells, to a lesser extent in the brain, ovaries, and T lymphocytes. Transferrin has a half-life of 8-11 days.
Iron in cytochrome enzymes
Cytochromes are electron-transferring proteins that contain heme as a prosthetic group. Cytochrome is a type of carrier protein that contains a heme group whose iron atom is isolated between Fe3+ and Fe2+. The structure consists of 3 helix, and the heme structure as a place for Fe. Various cytochromes are found in the respiratory chain, including cytochrome oxidase (aa3), b5, c, and P450. Cytochromes play a role in electron transfer. The electron transport chain is the final stage of the aerobic respiration reaction. Electron transport takes place in the cristae (inner membrane) of the mitochondrion. Molecules that play an important role in this reaction are NADH and FADH2 which are produced in the process of glycolysis, oxidative decarboxylation, and the Krebs cycle. 1.6
Iron in reserve form as ferritin and hemosiderin
Ferritin is one of the proteins that are important in the process of iron metabolism in the body. About 20 – 35% of the total amount of iron in the body is in the form of iron stores (depot iron), in the form of ferritin and hemosiderin. Under normal conditions, iron stores consist of 65% ferritin and 35% hemosiderin. 5
Ferritin is a protein complex that is globular in shape, has 24 protein subunits that compose it with a molecular weight of 450 kDa, found in all cells, both in prokayotic cells and in eukaryotic cells. Under normal circumstances, only a small amount of ferritin is present in human plasma. The amount of ferritin in plasma describes the amount of iron stored in our body. When viewed from the crystal structure, one ferritin monomer has five helix constituents, namely blue helix, orange helix, green helix, yellow helix and red helix where the Fe ion is in the middle of the five helix. In humans, the subunits that make up ferritin are of two types, namely Type L (Light) Polypeptide and Type H (Heavy) Polypeptide, which have molecular weights of 19 kD and 21 kD, respectively. Type L symbolized by FTL is located on chromosome 19 while Type H symbolized by FTH1 is located on chromosome 11. Each ferritin complex can store approximately 3000 – 4500 Fe3+ ions in it.
Ferritin and hemosiderin are mostly found in the spleen, liver and bone marrow. Ferritin is a water-soluble intracellular protein, which is an acute phase protein. Hemosiderin is the body’s iron reserves derived from partially degraded ferritin, found mainly in the bone marrow, and is insoluble in water. Under normal conditions, ferritin stores iron in the intracellular which can later be released back for use as needed. Serum ferritin is a reliable and sensitive parameter for determining iron stores in healthy people
Free iron is toxic to cells, because free iron is a catalyst for the formation of free radicals from Reactive Oxygen Species (ROS) through the Fenton reaction. For this reason, cells form a self-protection mechanism, namely by making iron bonds with ferritin
Iron balance in the body
The balance of iron in the body must be maintained so that anemia does not occur. Every day the turnover of iron is 35 mg, but not all of it must be obtained from food. Most of which is as much as 80-90% obtained from the breakdown of old erythrocytes, which are recycled to be used again by the bone marrow to form red blood cells. Factors that affect the balance of iron in the body are the food consumed, the number of erythrocytes in the body, the amount of oxygen in the body, and the influence of drugs. Ferritin is one of the keys that regulate iron hemostasis. Fe3+ stored in ferritin will be released again if the body needs it.1
Iron is needed by the body for oxygen transport, oxidative metabolism, and cell growth and proliferation. Iron in the body consists of functional compounds in metabolic and enzymatic, transport and storage forms of iron. Functional compounds that are bound to hemoglobin, myoglobin, and cytochromes. While the reserve components consist of ferritin and hemosiderin which are degradation of ferritin. Most components are bound to hemoglobin which functions to transport O2, while myoglobin is a protein that stores O2 reserves. While the reserve component is more in the form of ferritin than hemosiderin. Transport of iron is carried out by transferrin which is the least amount.
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4. Arkhipov A. Case study: myoglobin theoretical biophysics group. 2008. accessed from http://www.ks.uiuc.edu.
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6. The electron transport chain. available from https://www.tamu.edu.2003.
7. Storage iron metabolism. Accessed from http://www.omicsonline.org. 2012.
dr.Mahirina Marjani, SpA, Dr.dr.Nadirah Rasyid Ridha,M.Kes,Sp.A(K), Prof.Dr.dr.H.Dasril Daud,Sp.A(K)
PROGRAM PENDIDIKAN DOKTER SPESIALIS
DEPARTEMEN ILMU KESEHATAN ANAK