Understanding Sickle Cell Anemia through protein structure!

1. Understanding Sickle Cell Anemia through protein structure!

2. Introductory Comments: In this presentation you will learn about a genetic disease, that is caused by an error in the order of amino acids of one particular protein, hemoglobin. This error makes hemoglobin dysfunctional, and the red blood cells into rigid sickle-shape cells. This leads to symptoms that range from mild to severe and sometimes deadly. In the end of the presentation, answer the questions. Some or all of them might be on your test!

3. Sickle Cell Anemia • Symptoms • Inheritance • Normal Hemoglobin function • Mutated Hemoglobin • Back to the symptoms.

4. Symptoms Sickle Cell Anemia (SCA) is an inherited disease of the red blood cells. Red blood cells are where oxygen is carried from the lungs to the entire body. When one looks at patients’ blood under the microscope, one immediately notices that many of the patients’ red blood cells have the moon-like shape of a sickle, instead of the disc-like normal shape. Symptoms and Prognosis

5. So, what is wrong with the sickle cells? Well, normally, the disk shaped red blood cell are so flexible they can pass through the thinnest capillaries that are one-cell wide. The sickle-cells, however, are rigid, cannot pass through the thin capillaries, and even the arterioles. At times, these cells will pile up at a junction of the blood vessels, build up piles of cells that do not pass through, and prevent the blood supply to that whole area.

6. Traffic Jams by sickled cells

7. When this happens, the patient will experience severe pain in the affect area, and in many cases will be more vulnerable to infections, as well. You can read more about the symptoms of sickle cell anemia in http://library.thinkquest.org/06aug/00440/bsickleintro.html as well as other websites.

8. Sickle Cell Anemia • Symptoms • Inheritance • Normal Hemoglobin function • Mutated Hemoglobin • Back to the symptoms.

9. Since we did not study genetics yet, let’s mention shortly, that sickle cell anemia must be inherited from both parents to take an effect on the patient. Even if the parents have no symptoms, they can pass the disease to their children. You can learn more about the inheritance of the disease in http://www.search.com/reference/Sickle-cell_disease.

11. Sickle Cell Anemia • Symptoms • Inheritance • Normal Hemoglobin function • Mutated Hemoglobin • Back to the symptoms.

12. Hemoglobin (Hb) is a protein (287 amino acids long) that is highly abundant in red blood cells. In fact it is what gives red blood cells their color. The function of hemoglobin is to bind oxygen (in the lungs) and then release the oxygen where it is being used (in the tissues). Structure: Hemoglobin is made of 4 polypeptide chains (‘poly-amino acids’), 2 ‘alpha’ and 2 ‘beta’ chains. As follows:

13. alpha beta Heme beta alpha Hemoglobin: Four polypeptide chains, wrapped around one another.

14. Inside each of the four polypeptides there is also a special molecule called ‘Heme’, which contains an iron atom. It is this iron and this heme to where oxygen is bound when it is carried: O2 (This is why iron is so important in our diet!)

15. Normally, when the hemoglobin protein binds oxygen, it moves a little and changes its shape. Or it is said, that hemoglobin is changing from ‘deoxy-hemoglobin’ (no oxygen) into the oxygen bound ‘oxy-hemoglobin’ shape. When oxygen is released, it is deoxy-hemoglobin once again. Deoxy-Hb Oxy-Hb – O2 Release oxygen in the tissues Picked up oxygen in the lungs

16. Sickle Cell Anemia • Symptoms • Inheritance • Normal Hemoglobin function • Mutated Hemoglobin • Back to the symptoms.

17. As said before, hemoglobin is made of 287 amino acids. In sickle cell patients there is one amino acid out of the 287 that is different from the normal hemoglobin. Instead of the amino acid ‘glutamic acid’, there is a ‘Valine’ in that position. As a result, hemoglobin molecules become ‘sticky’ to one another, and they clump together:

19. Sickle Hemoglobin Normal Hemoglobin:

20. Why does this happen? Normal (with Valine) Mutated (with Glutamic Acid)

21. When clumped together, several things happen: A. Hemoglobin is no longer soluble in water. B. The hemoglobins that pile up form a fiber of hemoglobins that adopts a sickle-shape. C. The clumped hemoglobins can no longer bind oxygen.

22. Since there is so much hemoglobin in red blood cells, the shape of the cell becomes the shape of the hemoglobin fibers – a sickle shape.

23. Sickle Cell Anemia • Symptoms • Inheritance • Normal Hemoglobin function • Mutated Hemoglobin • Back to the symptoms.

24. This sickling of blood cells is what causes the unpleasant symptoms of the genetic disease: • The rigid nature of sickle blood cells prevents them from passing through the narrow capillaries. So they pile up in the entries to the capillaries and bock the blood flow. • The sickle cells cannot carry oxygen – hence the name ‘anemia’.

25. Questions: • What is the function of hemoglobin in the blood? • What is the overall structure of hemoglobin? How many amino acids is it made of? How many polypeptide chains? • What is the difference in structure between normal hemoglobin protein and a sickle cell ‘mutant’ protein? • What is the problem with sickle blood cells? • How does sickle cell anemia demonstrate the importance of a correct order of amino acids in a protein?