HEMOGLOBIN (Hb)
Structure of Hb The red, oxygen-carrying pigment in the red blood cells is hemoglobin, a protein with a molecular weight of 64,450.Hb is a globular molecule made up of 4 subunits. Each subunit contains a heme conjugated to a polypeptide (globin) i.e. Hb molecule consists of 4 protein chains and 4 heme groups . Each protein, called globin, is bound to one heme.Normal Hb concentration in the blood: The average normal Hb content of blood is 16g/dl in men and 14g/dl in women. O2 carrying capacity of the blood : One gram of Hb can bind with 1.34 ml of O2. Whole blood in healthy adults contains 15g of Hb per dl of blood thus. O2 capacity of blood = 1.34 mL O2 x gHb/dl. of blood. = 1.34 ml O2/gHb x 15gHb/dl = 20.1 ml O2 combine with Hb /dl blood. The heme portion of Hb molecule is synthesized from glycine and succinyl-CoA in mitochondria and globin in ribosomes
Structure of Heme:heme is a chemical structure made up of a porphyrin ring with an iron atom inserted in the center. Each heme is a red- pigment molecule containing one iron atom. The porphyrin is made up of 4 pyrrole rings . synthesis of heme takes place in the mitochondria.
Formation of Hemoglobin
The heme portion of the Hb is synthesized mainly from: Acetic acid is changed in the Krebs cycle into succinyl-CoAStructure of globin:The globin portion of the Hb is a protein (simple polypeptide chains made up of amino acids). There are two Paris of polypeptides in each Hb molecule, two of the subunits contain one type of polypeptides the other two contain another type of polypeptides. Synthesis of globin takes place in the polyribosomes. 1.Alpha chain(α) contain 141 amino acid residues. 2. Beta chain(β) contain146 amino acid residues. 3.Delta chain(δ) contain also 146 a.a. residues but differ from β chains by 10 a.a. residues. 4.gamma chain(γ) also contain 146 a. a. residues ,differ from β chain by 39 a.a. residues.
different types of normal Hb:1.Embryonic Hb: this Hb occur early in gestation:Gower 1.Gower 2.Portland.Embryonic Hb is replaced by:2.Fetal Hb (HbF α2γ2 ): which consist of two alpha– chains and two gamma – chains.Before birth, fetal Hb is gradually replaced by HbA. HbF has more affinity to oxygen than HbA because gamma chains combine to 2,3,DPG less avidly than HbA which have 2 beta chains.3.Adult Hb (HbA α2 β2): there are two types:HbA1: made up of two alpha chains + two beta chains. accounts for 97.5% of the total HbA. HbA2 (α2δ2): which consists of two alpha chains & two delta chains 2.5% of adult Hb is HbA2. Glycosylated Hb (HbA1c): consists of a minor variation of HbA1. It differs from normal HbA1 in that if has a molecule of glucose attached to the N -terminal valine of each beta - chains. The normal level of HbA1c in adults is 5% of adult hemoglobin.In diabetes mellitus the level of HbA1c is elevated.
Reactions of Hb : 1- Reaction of Hb with O2(oxygenation): Hb4 + O2 Hb4O2 Hb4O2 + O2 Hb4O4 Hb4O4 + O2 Hb4O6 Hb4O6 + O2 Hb4O8 oxyhemoglobin deoxyhemoglobin O2 attached to Fe+2 (ferrous iron) in the heme.
Reaction of Hb with CO2: CO2 is combine amino group of the globin molecule & not with iron atom and form carbamino hemoglobin (carbamino-Hb). 3- CO reacts with Hb to form carboxyhemoglobin (carbon monoxyhemoglobin). Cigarette smoke also contains CO and the blood of smokers contain 5% - 15% carboxyHb. Carbon monoxide is a poisonous substance. 4- When the blood is exposed to various drug and other oxidizing agents in vitro or in vivo, the ferrous iron (Fe++) in the hemoglobin molecule is converted to ferric iron (Fe+++) forming methemoglobin (metHb).
Formation of methemoglobin methemoglobin is a type of hemoglobin that contain ferric iron rather than ferrous . (oxidation of iron). Met-hemoglobin is useless as O2 carrier. A small amount of met-hemoglobin is present in the blood of normal individuals =0.3 g/dl OR 1.7% of total Hb. Increased met-hemoglobin result in met-hemoglobinemia. Causes : Oxidant drugs ex. Anti- malaria{ chloroquine and primaquine }or antibacterial drugs or certain food as fava- beans that cause oxidation of iron. The presence of NADH-met-hemoglobin reductase system convert Fe+3 to Fe+2 . congenital deficiency of this enzyme result in met-hemoglobinemia .
Hemoglobin
Position on β polypeptide chain of Hb 1 2 3 4 5 * 6 --------------------- 146HbA (normal) HbS(sickle cell)
Glutamic acid Valine
The erythrocyte contain an abnormal type of Hb called HbS. When this Hb is exposed to hypoxia, it precipitates into long crystals inside the erythrocyte which give it the appearance of a sickle rather than a biconcave disc.
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