Structure of Hemoglobin
Normal Hemoglobin and Sickle Hemoglobin
As we know, hemoglobin is a globular protein that is constructed of 4 polypeptide chains, two alpha and two beta. The amino acid sequence in the structure of normal hemoglobin has a Glutamate on the 6th amino Acid sequence. In Sickle Hemoglobin (also known as hemoglobin S) a Valine takes the place of the Glutamate. Valine is ionic and Glutamate is nonpolar. The side chain that contains Valine is exposed to the aqueous enviornment as you can see in the picture below. When a normal hemoglobin is in its deoxygenated state it will have a nonpolar cavity on the outside of the structure. The nonpolar Valine fits perfectly into that nonpolar cavity inhibiting the bonding spot for oxygen.
The change in the amino acid in the sequence causes the hemoglobin to want to bond with the neighboring hemoglobin. This bond forms strands of polymerized hemoglobin inhibiting the oxygen to bind with the hemoglobin. This causes the sickle shape of the cell.
- Quick Overview – Hemoglobin Types
F – normally found in fetuses and newborn children. Hemoglobin F is replaced by Hemoglobin A (adult hemoglobin) shortly after birth.
A – the most common type of hemoglobin found in adults.
A2 – a type of hemoglobin found in small amounts in adults.
S – the kind of hemoglobin found in people with sickle cell anemia.
C – another kind of hemoglobin found in people with sickle cell anemia.
The structure of hemoglobin is coded for on chromosome 11 with the gene symbol HBB. Hemoglobin molecules, which reside in red blood cells, are responsible for carrying oxygen from the lungs to various parts of the body for use in respiration. The HBB gene codes for one of the two types of polypeptide chains found in adult hemoglobin. Normal adult hemoglobin is a quaternary structure of protein consisting of two alpha helix chains and two beta pleated sheet chains. HBB codes for the beta chain, which is often referred to as beta globin. Mutant beta globin is responsible for the sickling of red blood cells seen in sickle cell anemia.
Hemoglobin S differs from regular adult hemoglobin (hemoglobin A) by just one single amino acid. A valine replaces a glutamine in the 6th position of the beta chain of globin.
Hemoglobin C disease is a recessive disorder that causes mild hemolytic anemia. This form of hemoglobin disease is often considered more benign of hemoglobin diseases. People with hemoglobin diseases may not even be diagnosed until they reach adult hood. This type of hemoglobin will cause sickle-cell anemia when C hemoglobin is trait from one parent is paired with the sickle S hemoglobin from the other parent, causing one in four children to be born with Sickle Hemoglobin C disease.
“Hemoglobin C comprises 2 normal alpha chains and 2 variant beta chains in which lysine has replaced glutamic acid at position 6.” This mutated form of hemoglobin precipitates crystals in the red blood cells. These crystals will cause an increase in the viscosity of the blood.
Crystals in hemoglobin C
A person with hemoglobin c paired with hemoglobin S often have the same health issues related to sickle-cell disease, but to a milder degree. In Sickle hemoglobin C disease the cells also become sickled, which can cause a block in the blood flow because the sickled shape of the cells causes a blockage in a blood vessel. Much like Sickle cell anemia people with the C hemoglobin may experience organ degradation from repeated sickling and anemia, and they are at a higher risks to get an infection.
Medscape, . “Hemoglobin C Disease.” eMedicine from web MD. Medscape, n.d. Web. 18 Nov 2010. http://emedicine.medscape.com/article/200853-overview.