Catral BSChE V Assignment in Biochemical Engineering
Sickle Cell Anemia Sickle cell anemia is a genetic disease that affects hemoglobin, the oxygen transport molecule in the blood. The disease gets its name from to the shape of the red blood cells under certain conditions. Some red blood cells become sickle-shaped and these elongated cells get stuck in small blood vessels so that parts of the body don't get the oxygen they need. Sickle cell anemia is caused by a single code letter change in the DNA. This in turn alters one of the amino acids in the hemoglobin protein. Valine sits in the position where glutamic acid should be as shown in Figure 1. The valine makes the hemoglobin molecules stick together, forming long fibers that distort the shape of the red blood cells, and this brings on an attack.
Figure 1. Valine replaces glutamic acid resulting in a sickle cell hemoglobin
In a molecular perspective, the mutation causing sickle cell anemia is a
single nucleotide substitution (A to T) in the codon for amino acid 6 as shown in Figure 2. The change converts a glutamic acid codon (GAG) to a valine codon (GTG). The form of hemoglobin in persons with sickle cell anemia is referred to as HbS. The nomenclature for normal adult hemoglobin protein is HbA1.
Figure 2. Change in codon 6 by single nucleotide substitution (A to T)
Active site of enzymes
This is a small portion of the surface of an enzyme where a specific chemical
reaction is catalyzed. Some physical and chemical interactions occur at this site to catalyze a certain chemical reaction for a certain enzyme.
Lock and Key Hypothesis
Enzymes are thought to operate on a geometric principle. The tertiary
and quaternary structures of an enzyme have the substrate binding sites, which have exactly the complementary shape of the substrate molecules. This helps in the binding of the appropriate substrate to the active centers just like a key fits in the keyhole as shown in Figure 3.
Figure 3. An enzyme and a substrate fits together as dictated by the lock and key hypothesis
Induced Fit Theory
Some enzymes change the shape of the active center slightly to
accommodate the substrate molecules, a process known as induced fit. The enzyme substrate complex thus formed lowers the energy of activation by either stressing an existing bond or correctly orienting two molecules to favor a reaction. The enzyme holds the substrate molecules in exactly the right position relative to each other to facilitate the reaction due to geometric and electrical configuration.