Haemoglobin

• Hb


  a globular protein; found in the cytoplasm of erythrocytes. a tetramer, 2 pairs of globis: 1 alpha and the other beta.

  alpha gene-chromosome 16

  beta gene-chromosome 11.
• Function

  -It acts as a gas transport protein i.e transports O2 from lungs to tisssues and CO2 from tissues to the lungs.

  -Reduces NO

  -Acid-base balance by binding to H+
• Quaternary structure

  spherical tetramer with 2 alpha and 2 beta globins. Each globin has a heme group with a centrally placed ferrous iron.
• Heme


  4 N atoms, 1 Fe2+ bound to a tetrapyrole ring by covalent bonds, double bonds.

  compounds with heme; hemoglobin, myoglobin, cytochromes, catalases, proteases.
• Types of Hb chains and combinations

  1)HbA1; 2 alpha and 2 beta->majority, 95-98% of total Hb

  2)HbA2; 2 alpha and 2 delta->minor, 2% of total Hb-16weeks after birth and increases in beta thalassaemias.

  3)HbF; 2 alpha and 2 gamma->mostly in fetal development and infants- binds to O2 with lower tension than HbA hence higher affinity.

  4)Hb-gower 1; 2 epsilon and 2 epsilon-> <5weeks embryogenic

  5)Hb-gower 2; 2 alpha and 2 epsilon-> 4-13 weeks embryonic

  6)Hb-Portland; 2 epsilon and 2 gamma->h

  7)HbS; GAG to GTG hence Glu to Val leading to sickle cell shape.

  8) HbA1C; glycated Hb and increases in DM.
• Haemoglobinopathies

  Haemolytic anemia-diagnosis

  • Family history of haemoglobinopathies
  • CBC and peripheral blood smear-sickle cells, Heinz bodies, spherocytes, basophilic stippling, polychromasia-lack of any of these cells doesn't r/o haemolytic anemia.
  • Electrophoresis or HPLC
  • Genetic studies.
• Hemoglobin


  Oxygen binding protein of red blood cells, a globular protein
• Hemoglobin molecule


  • Tetramer
  • Oxygen binding protein
  • Globular protein
• Hemoglobin


  Consists of four polypeptide subunits; 2 a chains and 2 non a
• Main function of red blood cell

  • Gas transport protein
  • Transfer of O2 from lungs to tissue
  • Transfer of CO2 from tissue to lungs
• Each red cell has 640 million molecules of Hb
• HbA


  2 a & 2 ẞ with heme, major form of Hb in adults and in children over 7 months
• HbA1


  Minor form of Hb in adults, forms only 2-3% of total Hb A
• Fetal Hb (Hb F)

  2 a and 2 y subunits, found in fetus and newborn infant
• Normal adult hemoglobin


  • Hb A
  • Hb A2
  • Hb F
• Hemoglobin


  Haemoprotein only found in the cytoplasm of erythrocytes
• Normal concentration of Hb in the blood

  • Adult males 13.5 - 17.5 g/dL
  • Adult females 12 - 15 g/dL
• Blood can carry very little oxygen in solution, hemoglobin is required to carry oxygen around
• Hemoglobin is 97% saturated when it leaves the lungs, under resting conditions it is about 75% saturated when it returns
• Hemoglobin


  Made from two similar proteins that "stick together", both proteins must be present for the hemoglobin to pick up and release oxygen normally
• a chain


  Consists of 141 Amino acids
• ẞ chain


  Consists of 146 Amino acids
• Structure of hemoglobin


  • Tetramer
  • Four polypeptide chains
  • Four heme groups
  • Helical structure with eight helical segments
• Heme


  Iron of heme is covalently bound to histamine at Position F on H Segment
• Synthesis of Hemoglobin (Hb)


  1. Heme in mitochondria

  2. Globin in ribosomes

  3. Well synchronized
• Heme


  Ferrous protoporphyrin IX, essential for all cells as a prosthetic group in hemoproteins
• Heme synthesis


  8 major steps in the erythroblasts and reticulocytes-mitochondria and cytosol
• Globin synthesis


  Starts at 3rd week of gestation, various types of globin combine with heme to form different hemoglobins
• Hemoglobins


  • Embryonic: Hb Gower I, Hb Gower II, Hb Portland
  • Fetal: HbF, HbA
  • Adult: HbA, HbA2, HbF
• Hemoglobin


  • Globular hemoprotein
  • Heme is a complex of protoporphyrin IX & ferrous iron (Fe2+)
  • Iron is held in the center of the heme molecule by bonds to the four nitrogens of the porphyrin ring
  • One position is coordinated to the side chain of a histidine amino acid of the globin molecule, the other position is available to bind oxygen
• Globin of hemoglobin


  Globular protein with a quaternary structure
• Chaperones


  Proteins that facilitate the folding of other proteins, many are heat-shock proteins
• Hsp70 and Hsp60 families


  Useful for hemoglobin folding, Hsp70 stabilize unfolded polypeptide chains, Hsp60 facilitate the folding of proteins into their native conformations
• Protein disulfide isomerase and peptidyl prolyl isomerase


  Enzymes that catalyze protein folding by breaking and re-forming covalent bonds
• The simplest level of protein structure, primary structure, is simply the sequence of amino acids in a polypeptide chain
• Hsp70 and Hsp60 families

  Useful for Hb folding
• Members of the Hsp70 family

  • Stabilize unfolded polypeptide chains
• Members of the Hsp60 family (also called chaperonins)


  • Facilitate the folding of proteins into their native conformations
• Chaperones


  Facilitate protein folding by binding to and stabilizing partially folded intermediates
• Protein disulfide isomerase


  Enzyme that catalyzes protein folding by breaking and re-forming covalent bonds