Why Is Sickle Cell Anemia a Molecular Disease

The Nobel Prize chemist Linus Pauling related the mechanism of sickle cell anemia to a genetic defect in hemoglobin synthesis and thus defined the first molecular disease. Pauling s groundbreaking paper in 1949 was boldly titled Sickle Cell Anemia A Molecular Disease. 1 Many claim that this discovery laid the foundation for molecular biology. What is the chemistry that is at the heart of this pioneering work  

Normal hemoglobin molecules are complex, three-dimensional structures consisting of four chains of amino acids known as polypeptide chains. Two of these chains are known as alpha subunits with 141 amino acid residues each, and the remaining polypeptide chains are the beta subunits with 146 amino acid residues each. The sequences of amino acids in the alpha and beta subunits are different, but fold up via noncovalent interactions to form similar three-dimensional structures. When a polypeptide chain arranges itself in space, i.e., when it folds, amino acids that were far apart in the chain are brought closer in proximity. The final overall shape of the protein molecule is influenced by (1) the amino acids in the chain, and (2) the interactions that are possible between distant amino acids. 

One of the amino acids in the beta polypeptide chain of hemoglobin is glutamic acid (Fig. 7.11.1). 

The hydrophilic polar side group on glutamic acid is capable of forming hydrogen bonds with water and thus helps to keep normal hemoglobin dispersed within the red blood cells. 

In sickle cell hemoglobin, the glutamic acid of the beta subunit is replaced by the amino acid valine (Fig. 7.11.2). Even though only this one amino acid is 

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Question 7.11 Why Is Sickle Cell Anemia a Molecular Disease ... 

Why is sickle cell anemia called a molecular disease ... 

Why is sickle cell anemia called a molecular disease Draw the structures of the dipeptides that can be formed from the reaction between the amino acids glycine and valine. 

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