Hemoglobin: Structure, Function and its Properties

Hemoglobin is the main component of red blood cells, and they help carry oxygen throughout the body and regulate the amount of oxygen supplied to tissues. Hemoglobin cannot be produced in the body alone and is produced and stored by the amount of hemoglobin in the body is maintained at a steady level.

The average person has a hemoglobin count of 14.8 grams per 100 ml of blood. Let us check the details of what is the structure and function of hemoglobin.

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. The heme group binds oxygen and carbon dioxide and imparts a red color to the blood; it is also spelled hemoglobin.

• Why Proteins are Very Important? How to Explain?
• Peptide bonds: Backbone of the Proteins
• What is Amino acid and its Structural Chemistry?

Historical Aspects of Hemoglobin Discovery

• In 1665, Marcello Malpighi described the RBCs.
• Felix Hope Seyler, in 1862, isolated pure hemoglobin.
• In 1904, Christian Bohr 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.

Structure of Hemoglobin

let me explain the structure of haemoglobin. Here is the details of hb molecule structure.

• 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 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.
• The globin part comprises four polypeptide chains, two identical polypeptide chain in hemoglobin. They are 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.
• The Hb molecule contains hydrophobic amino acids and hydrophilic ones on the surface.
• Heme pockets of α-subunits are just the adequate size to allow entry of an O2 molecule. Entry f O2 into heme pockets of β-subunits is blocked by a valine residue.
• Varieties of average 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%.

Globin Proteins

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

Importance of Hemoglobin

• 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 provides an insight into the molecular basis of hemoglobinopathies.

Hemoglobin derivatives

• Hemin (Hematin hydrochloride)
• Hemochromogen
• Hematoid
• Methemoglobin (an oxidation product of Hb; produced by drugs like nitrates, phenacetin, sulphonamide drugs; lack of enzymes like methemoglobin reductase, diaphorase-I, HbM.
• The toxic effects of Met Hb are cyanosis, fatigue, tachycardia, tachypnea, and depression.
• Methemalbumin: (a combination of hematin and albumin), not present in normal adult blood. When present, it indicates intravascular hemolysis, detected by Schumm’s test.

Combination of Hb with gases

• Oxyhemoglobin: (loose and reversible combination with O2); 1.34ml O2 combined with each gm of Hb.
  • One mole of Hb can maximally connect with four moles of O2. The partial pressure of O2 favors oxygenation.
  • The partial pressure of CO2 favors dissociation. Acidosis favors liberation of O2.
  • Oxygenated Hb is relaxed, i.e., in an “R” state. R state is characterized by removing valine residue from the heme pocket of β-subunit with broken salt bridges; it cannot bind BPG; FFe++ comes in the plane of the porphyrin ring; heme-heme interaction increases the affinity for O2; histidines of β-chains release protons (H+).
• Deoxygenated Hb: In “T” form, i.e., taut form, salt bridges plenty and intact, valine residue covers the heme pocket of β-chain and does not allow entry of O2; can bind BPG; F++ out of the plane of the porphyrin ring; low affinity for O2; β-chain histidine residue protonated (H+ added).
• Carboxyhemoglobin (Hb+ carbo monoxide): Firmer combination, not reversible, the association of Hb to CO is 210 times more than 2; it inhibits cytochrome oxidase of the 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., Thalassemia.
• 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
• interfering with mRNA formation, e.g., Hb constant spring

HbS

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

Thalassemias

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

Frequently Asked Questions (FAQs)

Final words

Hemoglobin is a complex protein molecule that is found in red blood cells. It is composed of heme groups, which are made up of porphyrin rings and amino acids. Hemoglobin is responsible for transporting oxygen and carbon dioxide through the bloodstream. Hemoglobin comprises four subunits, two alpha and two betas. This blog will explain the structure of hemoglobin and how it works.

Red blood cells are essential in our lives, and they provide oxygen to our tissues and organs. Hemoglobin is the main component of red blood cells, and they help carry oxygen throughout the body and regulate the amount of oxygen supplied to tissues.