Princess Janine B.

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.