Hemoglobin y hà nội

HEMOGLOBIN HEMOGLOBIN  is a hemoprotein only found in the cytoplasm of erythrocytes (ery) normal concentration of Hb in the blood: adult males 13.5 – 16.5 g/dL adult females 12 – 15 g/dL  HEMOGLOBIN  Blood can carry very little oxygen in solution  Hemoglobin is required to carry oxygen around  Hemoglobin is found in red blood cells HEMOGLOBIN In fact if the body had to depend upon dissolved oxygen in the plasma to supply oxygen to the cells –  The heart would have to pump 140 liters per minute instead of liters per minute  HEMOGLOBIN  Each red cell has 640 million molecules of Hb  Hemoglobin is 97% saturated when it leaves the lungs  Under resting conditions is it about 75% saturated when it returns HEMOGLOBIN  Hemoglobin is made from two similar proteins that "stick together"  Both proteins must be present for the hemoglobin to pick up and release oxygen normally  One of the component proteins is called alpha, the other is beta HEMOGLOBIN    Blood cells are made up of two components The hemoglobin is in solution inside the cell The cell is surrounded by a membrane that holds in the hemoglobin STRUCTURE OF HEMOGLOBIN • • Hb is a spherical molecule consisting of peptide subunits (globins) = quartenary structure Hb of adults (Hb A) is a tetramer consisting of - and β-globins → each globin contains heme group with a central Fe2+ ion (ferrous ion) HEME STRUCTURE HEME IS A METALOPORPHYRINE (CYCLIC TETRAPYRROLE) Heme    contains: conjugated system of double bonds → red colour nitrogen (N) atoms iron cation (Fe2+) → bound in the middle of tetrapyrrole skelet by coordination methine bridge covalent bonds pyrrole ring OXY & DEOXYHAEMOGLOBIN HB-OXYGEN DISSOCIATION CURVE HB-OXYGEN DISSOCIATION CURVE  The normal position of curve depends on Concentration of 2,3-DPG  H+ ion concentration (pH)  CO in red blood cells   Structure of Hb HB-OXYGEN DISSOCIATION CURVE  Right shift (easy oxygen delivery) High 2,3-DPG  High H+  High CO    HbS Left shift (give up oxygen less readily) Low 2,3-DPG  HbF  ADULT HAEMOBLOBIN Hb A Hb A2 Hb F structure a22 a2d2 a22 Normal % 96-98 % 1.5-3.2 % 0.5-0.8 % TYPES OF HEMOGLOBIN Adult Hb (Hb A) = α and β subunits HbA1 is the major form of Hb in adults and in children over months HbA2 (2 α, δ) is a minor form of Hb in adults It forms only – 3% of a total Hb A  Fetal Hb (Hb F) = α and γ subunits - in fetus and newborn infants Hb F binds O2 at lower tension than Hb A → Hb F has a higher affinity to O2 After birth, Hb F is replaced by Hb A during the first few months of life  Hb S – in β-globin chain Glu is replaced by Val = an abnormal Hb typical for sickle cell anemia  DERIVATIVES OF HEMOGLOBIN  Oxyhemoglobin (oxyHb) = Hb with O2  Deoxyhemoglobin (deoxyHb) = Hb without O2 Methemoglobin (metHb) contains Fe3+ instead of Fe2+ in heme groups  Carbonylhemoglobin (HbCO) – CO binds to Fe2+ in heme in case of CO poisoning or smoking CO has 200x higher affinity to Fe 2+ than O2  Carbaminohemoglobin (HbCO2) - CO2 is non-covalently bound to globin chain of Hb HbCO2 transports CO2 in blood (about 23%)  Glycohemoglobin (HbA1c) is formed spontaneously by nonenzymatic reaction with Glc People with DM have more HbA1c than normal (› 7%) Measurement of blood HbA1c is useful to get info about long-term control of glycemia  Mutations in hemoglobin (hemoglobinopathies: 1- Sickle cell anemia (Hb S disease): It is a genetic disorder of blood caused by mutation in βglobin chain resulting in the formation of Hb S The mutation occurs in 6th position of β-chain where glutamic acid is replaced by valine (non polar) Valine residues aggregate together by hydrophobic interactions leading to precipitation of Hb within RBCs RBCs assume sickleshaped leading to fragility of their walls and high rate of hemolysis Such sickled cells frequently block flow of blood in narrow capillaries and block blood supply to tissue (tissue anoxia) causing pain and cell death Note: The lifetime of erythrocyte in sickle cell is less than 20 days, compared to 120 days for normal RBCs Patients may be : - Heterozygotes (Hb AS): mutation occurs only in one βglobin chain These patients have sickle cell trait with no clinical symptoms and can have normal life span Or: Homozygotes (Hb SS): mutation occurs in both βglobin chain with apparent anemia and its symptoms 2- Hb C disease: Like HbS, Hb C is a mutant Hb in which glutamic acid in 6th position of β-chain is replaced by lysine RBCs will be large oblong and hexagonal The heterozygous form (HbAC) is asymptomatic The homozygous form (Hb CC) causes anemia, tissue anoxia and severe pain 3- Thalassemia: A group of genetic diseases in which a defect occur in the rate of synthesis of one or more of Hb chains, but the chains are structurally normal This due to defect or absence of one or more of genes responsible for synthesis of α or β chains leading to premature death of RBCs Types: β -thalassemia: When synthesis of β chains is decreased or absent There are two copies of the gene responsible for synthesis of β chains Individuals with β globin gene defects have either : -β -thalassemia minor (β –thalassemia trait) : when the synthesis of only one β –globin gene is defective or absent Those individuals make some β chains and usually not need specific treatment -β -thalassemia major ( Cooley anemia): if both genes are defective -Babies will be severely anemic during the first or second year of life and so require regular blood transfusion Bone marrow replacement is more -α-thalassemia: in which synthesis of α globin chain is defective or absent There are four copies of gene responsible for synthesis of α globin chains so patients may have: i - Silent carrier of α-thalassemia with no symptoms: if one gene is defective ii- α-thalassemia trait: if two genes are defective Minor anemia present iii- Hb H disease - if three genes are defective Moderate anemia present iv Hydrops fetalis – Lacks all genes Fetus may survive till birth then dies ... DERIVATIVES OF HEMOGLOBIN  Oxyhemoglobin (oxyHb) = Hb with O2  Deoxyhemoglobin (deoxyHb) = Hb without O2 Methemoglobin (metHb) contains Fe3+ instead of Fe2+ in heme groups  Carbonylhemoglobin... beta HEMOGLOBIN    Blood cells are made up of two components The hemoglobin is in solution inside the cell The cell is surrounded by a membrane that holds in the hemoglobin STRUCTURE OF HEMOGLOBIN. .. HEMOGLOBIN  Blood can carry very little oxygen in solution  Hemoglobin is required to carry oxygen around  Hemoglobin is found in red blood cells HEMOGLOBIN In fact if the body had to depend upon dissolved