Molecular Biology of Sickle Cell Anemia - Term Paper Example

This reduces the oxygen carrying capacity of the blood and causes the jamming of blood vessels. One of the characteristic symptoms of sickle cell anemia is pain. Sickle cell anemia is found mainly in people belonging to malaria endemic regions for e.g. Africa. A definitive cure for this debilitating illness is yet to be found and so the treatment given to the patients is still largely symptomatic and supportive. (Taylor et al. 1997 pp.859) (Abnormal phospholipid molecular species of erythrocytes in sickle cell anemia, Connor et al. 1997) Hemoglobin: Structure The structure of the hemoglobin molecule was deciphered by scientists, Kendrew and Perutz using X-ray crystallography in 1959.

Hemoglobin is an oxygen-carrying chromoprotein. It is found in red blood cells of vertebrates. 1 red blood cell contains approximately 600 million hemoglobin molecules. It consists of 4 Heme molecules which are attached to 4 polypeptide or globin chains. Heme is a cyclic tetrapyrrole i.e. it consists of 4 molecules of pyrrole. It imparts a red color due to the methyl, vinyl and proprionate groups attached to it. Each heme group also contains one ferrous ion (prosthetic group)present in the porphyrin ring which is present in the center of the heme.

The 4 globin chains that make up a hemoglobin molecule are known as ?and ? chains. The two ?chains each contain 141 amino acids, while the two ?chains contain 146 amino acids. These chains are derived mainly from chromosome 16 and 11. Hemoglobin is a globular protein and the 4 protein chains are held together in what is known as a quaternary structure. The hydrophobic parts of the chains point inwards towards the molecule, whereas the hydrophilic parts point outwards. This makes the molecule soluble in water.

(Taylor et al. 1997 pp103, 859) (Interactive-Biology 2012) (The Molecular Biology of Sickle Cell Anemia, 2003)(Hemoglobin: Molecular modeling, 2011) Hemoglobin: Function The hemoglobin molecule is responsible for the transport of oxygen from the lungs to the cells of the body. Each oxygen molecule is attached to the ferrous ion in each heme group. Thus, one hemoglobin molecule is capable of carrying 8 oxygen atoms at a time. It also carries the carbon dioxide molecules back to the lungs for excretion.

Carbon dioxide is carried in three forms: in solution, as carbamino-hemoglobin and as bicarbonate ions.(Taylor et al. 1997 pp.479, 481) The hemoglobin molecule shows cooperative binding kinetics, i.e. when one oxygen molecules has been attached, the binding of the rest of the oxygen molecules becomes easier. The oxygen-dissociation curve is sigmoid. It shows that at low partial pressures of oxygen, the hemoglobin molecule readily gives up oxygen, which is then used up by the tissues. Increased concentrations of carbon dioxide also cause the release of oxygen from the molecule.

Under these conditions the curve shifts to the right. This is known as the Bohr Effect. (Taylor et al. 1997 pp.479-480) Hemoglobin: Synthesis Hemoglobin synthesis starts to occur in the proerythroblast stage of the RBC cycle. The molecule is produced by mitochondria and ribosomes in a series of reactions. Heme is synthesized in the mitochondria. Glycine &succinyl-CoA condense to form ?-aminolevulinic acid (ALA). This reaction occurs in the presence of ALA-synthase. ALA exits the