Question

Oxygen is carried from the lungs to tissues by the protein hemoglobin in red blood cells. Sickle cell anemia is a disease resulting from abnormal hemoglobin molecules in which a valine is substituted for a single glutamic acid in normal hemoglobin. How might this substitution affect the structure of hemoglobin?

Short answer

The substitution of valine for glutamic acid in normal hemoglobin changes the chemical properties of the amino acid, leading to the formation of hydrophobic patches on the hemoglobin surface. These patches cause hemoglobin molecules to stick together and form polymers, resulting in the deformation of red blood cells into a sickle shape. This altered structure negatively impacts hemoglobin's ability to carry oxygen, causing the symptoms of sickle cell anemia.

Step-by-step solution

Understanding hemoglobin structure

Hemoglobin is a protein in red blood cells that carries oxygen from the lungs to the tissues. It is composed of four subunits, each containing a heme group and a globin chain. The globin chains are made up of amino acids, which determine the structure and function of the protein. Amino acids play a crucial role in determining the protein structure as they form various interactions like hydrogen bonds, ionic interactions, Van der Waals, and disulfide bridges, which ultimately dictate their three-dimensional shape.

Examining the amino acid substitution

Sickle cell anemia is caused by a single amino acid substitution in the hemoglobin protein. In this case, valine (a nonpolar amino acid) replaces glutamic acid (a polar amino acid). The chemical properties of these amino acids are different; glutamic acid is hydrophilic (water-loving) due to its polar side chain, whereas valine is hydrophobic (water-hating) because of its nonpolar side chain. This change in chemical properties will affect the protein structure and the resulting interactions between amino acids.

Understanding the consequences of the substitution

The substitution of valine for glutamic acid in hemoglobin alters the structure and properties of the protein. Due to the hydrophobic nature of valine, it tends to cluster with other hydrophobic amino acids rather than interacting with water molecules, leading to the formation of hydrophobic patches on the hemoglobin surface. These hydrophobic patches cause the hemoglobin molecules to stick together, forming long fibers known as polymers inside the red blood cells. This, in turn, leads to the deformation of red blood cells into a sickle shape, causing sickle cell anemia.

Effects on the protein function

The altered structure of hemoglobin due to the amino acid substitution negatively impacts its function. The formation of polymers and the sickling of red blood cells impairs the ability of hemoglobin to carry oxygen effectively, leading to the characteristic symptoms of sickle cell anemia. The sickle-shaped red blood cells are less flexible and more prone to clogging blood vessels, leading to pain, tissue damage, and even organ failure. In conclusion, the substitution of valine for glutamic acid in normal hemoglobin affects the protein's structure and its ability to carry oxygen, ultimately causing sickle cell anemia. Understanding the role of amino acids in protein structure helps us better comprehend the molecular basis of diseases and develop targeted therapies for such conditions.