Hemoglobin and Sickle Cell Anemia - Lecture Notes | ISAT 454, Papers of Humanities

Download Hemoglobin and Sickle Cell Anemia - Lecture Notes | ISAT 454 and more Papers Humanities in PDF only on Docsity!

Hemoglobin and Sickle Cell Anemia

By

Nate Auchter

Matt Brenneman

Kelly Grennan

Kristen Zrioka

ISAT 454

January 28, 2002

Dr. Klevickis

Biological diversity comes about gradually over millions of years by the successful incorporation of genetic mutations into genomes. Although there are many forms of mutated hemoglobin, very few affect the health of the individual. Sickle cell anemia is the result of a human genetic mutation that affects the shape and function of red blood cells and can be very detrimental to the health of those with the disease. It is an inherited trait that is predominantly known for affecting African ancestry, but also people from Arabia, Greece, Italy, Latin America, and India. It is a recessive trait, meaning that both copies of the chromosomes must contain the mutation to cause the disease and those with only one copy are considered ‘carriers’ but do not suffer from sickle cell anemia. Sickle cell is caused by a single gene mutation causes the production of the amino acid valine rather than the amino acid glutamate in the beta chains on the surface of the hemoglobin. Where these substitutions occur, a new hydrophobic location is created on the surface of the hemoglobin. It is a single gene mutation. Figure 1: The following graphics show the structural differences between an atom of valine and an atom of glutamate. Oxygen molecules are shown in red, sodium in blue and carbon in gray. Glutamate Valine

Hemoglobin is the protein found in the blood that is responsible for transporting oxygen from the lungs to the other tissues in the body. It is formed by four polypeptide chains, alpha 1, beta 1, alpha 2, and beta 2, each of which contains a heme group. Each heme group is a ring-like structure that contains an iron molecule that is capable of binding to an oxygen atom. These four subunits work together through a signaling process known as ‘cooperativity’ as they collect and release oxygen throughout the body. This process is what ensures that the hemoglobin will collect oxygen in the lungs and will release it slowly as it travels through the body. Figure 2: Below is a model of simply the heme group and the atoms that compose it created using the PDB file 1AJ9 by J. Wilson, K.Phillips, and B. Luisi using Rasmol version 2.7 by Herbert Bernstein. We can clearly see that the group is composed of predominately carbon, with the binding region for the O 2 molecules in the center, on the atom of Fe, surrounded by nitrogen.

Figure 3 : This picture is the full hemoglobin protein created using the PDB file 1BIJ by Konnert and Hendrickson using Rasmol version 2.7 by Herbert Bernstein. Each of the four chains are colored differently, and each of the four heme groups are again colored in red. The iron(colored black) in the center of each of the hemes is more clearly visible in this picture. A deoxy-hemoglobin protein, one without any oxygen, has little attraction to oxygen molecules but once one sub-unit’s heme group attaches to an oxygen, it increases the attraction of the next sub-unit. This is caused due to a change in shape of the first protein sub-unit that occurs when the oxygen binds. This change of shape affects the next sub-unit and makes oxygen bind much faster and tighter to that heme group. This chain reaction occurs until the iron of all four heme groups are bound to oxygen. This same principle applies in the release of oxygen. The oxygen is bound most tightly in the lungs and until the first heme group releases its oxygen. Once it releases the oxygen, the sub- unit changes shape and affects the next sub-unit group making it easier for it to release its oxygen.

hemoglobin can no longer transport oxygen effectively and their rigid shape deforms the red blood cells giving them a sickle shape. Normal hemoglobin is a round, flexible shape and can easily move through the vessels of the body. Sickle shaped red blood cells can not do so and cause pain and buildup throughout the blood system causing blockages and limiting oxygen supply throughout the body Figure 5 :This illustration was created using the PDB file 2HBS created by D.J. Harrington, K. Adachi, and W.E. Royer Jr., 1997 using RasMol Version 2.7 written by Hubert Bernstein. It shows two hemoglobin molecules that are connected by valine 6 atoms. When this occurs the hemoglobin forms stiff chains that pull the red blood cells into a sickle shape. Those persons diagnosed with sickle cell anemia have a number of health complications because the sickle cells break apart and block blood flow through capillaries. Sickled cells also only survive 10 to 20 days as compared to the normal lifespan of 120 days of healthy red blood cells. This causes the patient to suffer from chronic anemia since the body can not replace these lost cells fast enough and there is not enough oxygen being transported throughout the body. Patients with sickle cell anemia may experience all or none of the following symptoms, pain episodes, dizziness, headaches, strokes, increased infection, leg ulcers, bone damage, yellow eyes or jaundice, early gallstones, lung blockage, kidney damage, and other symptoms. Those with the trait experience severe symptoms when they are in environments of extreme pressure or low oxygen. Red and blue distinguish between two hemoglobins Yellow = Val 6 Purple = heme Orange = iron

Although this disease can not be cured, there are certain treatments that can help to minimize symptoms. It is important for those suffering from sickle cell anemia to take folic acid daily as this aids in the production of new red blood cells. It is also important to drink plenty of water as the condition is aggravated if the body is dehydrated. It is also important to avoid extreme temperatures and over exertion because this can increase the demand for oxygen in the body and ultimately cause more cells to sickle as the oxygen is used. The sickle cell trait is known as a balanced polymorphism. Although those with two mutated copies of the gene suffer from sickle cell disease, those who are just have one mutated copy seem to be protected against malaria. This protection is important as malaria is responsible for 25% of all deaths in the human population. Although those with 2 mutated copies tend to suffer and die at a young age with no children, in some parts of the world those people with two non-sickle cell copies of the gene die young from mylaria. Being heterozygous for this trait enables the carrier to have enough regular blood cells to function normally yet enough sickle cells to be protected from mylaria which is what enables the population to survive. Figure 6 : These graphics from the Sickle Cell Information Center show the difference between normal red blood cells (shaped like doughnuts) and sickle cells; the arrows point to the sickle cells in this blood smear.