Hemoglobin: Structure, Function and its Properties

  • Marcello Malpighi described the RBCs in 1665.
  • Felix Hope Seyler in 1862 isolated pure Hemoglobin.
  • Christian Bohr in 1904 discovered that hemoglobin is the transporter of oxygen.
  • In 1912 Kutster established the structure of hemoglobin.
  • Hans Fischer synthesized heme in the laboratory in 1920 (Nobel prize, 1930).
  • In 1945, Linus Pauling (Nobel prize, 1954) described abnormal hemoglobins.
  • Max Perutz (Nobel Prize, 1962) studied the 3D structure of Hemoglobin.
hemoglobin structure and types

What is Hemoglobin?

Hemoglobin is a globular heme protein in vertebrate red blood cells and in the plasma of many invertebrates that carries oxygen and carbon dioxide; heme group binds oxygen and carbon dioxide and as well as imparts a red color to the blood; also spelled as hemoglobin.

Introduction of Hemoglobin Protein

  • Red-colored conjugated protein (made up of heme and Globin) present inside the RBC
  • Normal Hb% in an adult male is 14 to 16 gm.
  • Approximately 6.25 gm of Hb are synthesized and destroyed every day.
  • Heme structure does not vary from species to species.
  • It is the basic protein globin that varies in amino acid composition and sequence in different species.
  • Globin is rich in Histidine and lysine.


  • Hb binds O2 transports O2 and delivers the same to tissues.
  • Hb binds CO2, a waste product of metabolism.
  • 2-3 BPG, produced in RBC by Rapport-Leubering shunt stabilizes Hb confirmation at the quaternary level and enhances dissociation of O2 from Hb at the tissue site.
  • Cyanide combines with methemoglobin to form cyanomethemoglobin which is non-toxic.
  • The study of Hb structure gives an insight into the molecular basis of hemoglobinopathies.

Structure of Hemoglobin

  • Heme is an iron porphyrin compound. Porphyrin is a tetrapyrrole structure.
  • Ferrous iron occupies the center of the porphyrin ring and establishes linkages with all the four nitrogens of all the pyrrole rings.
  • It is also linked to the nitrogen of the imidazole ring of histidine present in the globin part.
  • Globin part is made of four polypeptide chains, to identical α-chains and two identical β-chains in normal adult hemoglobin.
  • Each chain contains a “heme” in the so-called ‘heme pocket’. So one Hb molecule possesses four heme units.
  • Hb molecule contains hydrophobic amino acids inside and hydrophilic ones on the surface.
  • Heme pockets of α-subunits are of just adequate size to give entry to an O2 molecule. Entry f O2 into heme pockets of β-subunits is blocked by a valine residue.
  • Varieties of normal human Hb are
    • Hb-A1 (two α-chains and β-chains)
    • HbF (two α-chains and ¥-chains)
    • Hb-A2 (two α-chains and delta-chains)
    • Embryonic Hb (two α-chains and €-chains)
    • Hb-A3 (Altered from Hb-A found in old red cells)
    • HbA1C (Glycosylated Hb, present in a concentration of 3-5% of total Hb). In diabetes mellitus, it is increased to 6 to 15%.

Hemoglobin derivatives

  • Hemin (Hematin hydrochloride)
  • Hemochromogen
  • Hematoidin
  • Methemoglobin (an Oxidation product of Hb; produced by drugs like nitrites, phenacetin, sulphonamide drugs; lack of enzymes like methemoglobin reductase, diaphorase-I, HbM.
  • Toxic effects of Met Hb are cyanosis, fatigue, tachycardia, tachypnea, depression.
  • Methemalbumin: (Combination of hematin with albumin), not present in normal adult blood, when present indicates intravascular hemolysis, detected by Schumm’s test.

Combination of Hb with gases

  • Oxyhemoglobin: (loose and reversible combination with O2); 1.34ml O2 combines with each gm of Hb.
    • One mole of Hb can maximally combine with four mols of O2. The partial pressure of O2 favors oxygenation.
    • Partial pressure of CO2 favors dissociation. Acidosis favors liberation of O2.
    • Oxygenated Hb is in a relaxed state i.e, ‘R’ state. R state characterized by the removal of valine residue from heme pocket of β-subunit; broken salt bridges; cannot bind BPG; FFe++ comes in the plane of porphyrin ring; Heme-Heme interaction increases the affinity to O2; Histidines ofβ-chains release protons (H+).
  • Deoxygenated Hb: In “T” form i.e. Taut form, salt bridges plenty and intact, valine residue covers heme pocket of β-chain and does not allow entry of O2; can bind BPG; F++ out of the plane of porphyrin ring; low affinity to O2; β-chain histidine residue protonated (H+ added).
  • Carboxyhemoglobin (Hb+ carbo monoxide): Firmer combination, not reversible, the affinity of Hb to CO in 210 times more than )2; inhibits cytochrome oxidase of electron transport chain.
  • Carbamino Hb (Hb + CO2):
  • Sulfhaemoglobin: Greenish pigment; formed when H2S reacts with Oxy-Hb, seen in severe constipation, certain types of bacteria.

Abnormal Haemoglobins

More than 30 abnormal types descry, differentiated by their characteristic electrophoretic mobilities, generally transmitted; are due to the single mutant gene; Two types –

  • Due to the mutation of the structural gene. E.g: HbS, HbM, HbC, HbD (Punjab) etc.
  • Due to a mutation in the regulator gene. E.g: Thalassemias.
  • Detection by Finger Printing techniques and Hybridization

Effects of abnormal Hb

  • Changed Red cell morphology
  • Hemolytic anemia, Jaundice
  • Methemoglobinemia
  • High O2 affinity E.g: Hb cheaper, Hb-Rainier
  • Interfere with mRNA formation e.g.: Hb constant spring


In both β-chains glutamic acid in the 6th position is replaced by Valine. This results in an increase in viscosity and precipitation of HbS. Hence the crescent or sickle-shaped RBC of more fragile nature. However such RBCs show increased resistance to malaria but more vulnerable to salmonella infections.


  • α-chain Thalassemia: Synthesis of α-chains is replaced. E.g.: HbH (β4) and Hb-Barts (¥4).
  • β-chain Thalassemia (Thalassemia major): Synthesis of β-chain is repressed. As a result, increased synthesis of HbA2 or HbF.

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