Sickle cell anemia is a genetic disorder that affects the protein hemoglobin, of which red blood cells are primarily composed. Individuals with sickle cell anemia have misshapen red blood cells that tend to accumulate in vessels and create small clots, leading to organ damage and pain. The disease arises from a miscoded portion of the genes, or DNA, for hemoglobin, which results in a faulty amino acid sequence.
Features
Sickle cell anemia, explains the National Heart Lung and Blood Institute, is the result of a genetic mutation that can be spread from parent to offspring and produces misshapen red blood cells. While normal red blood cells have a biconcave shape, making them similar in appearance to a doughnut with an incomplete hole in the center, sickled cells look like quarter moons. They stick to one another, instead of slipping past each other in blood vessels, and have short life spans compared to healthy cells.
Chemical Basis
The reason sickled red blood cells have such an odd shape is that they're made up of misshapen hemoglobin. Hemoglobin is a protein, a member of the same class of molecules that make up muscles and connective tissue like collagen. Instead of acting as structural material like collagen, however, the hemoglobin protein carries oxygen. Like all proteins, explain Drs. Mary Campbell and Shawn Farrell, hemoglobin is made up of a long string of amino acids.
Mutations
The body makes proteins by stringing amino acids together in a specific sequence, the instructions for which are coded into the genetic material, or DNA. In their text "Biochemistry," Drs. Reginald Garrett and Charles Grisham explain that mistakes in DNA result in mistakes in amino acid sequences. There are 20 types of naturally occurring amino acids, which can be put together in any sequence or combination to make proteins that vary in length from tens to thousands of amino acid units. Even a single incorrect amino acid significantly affects the function of a protein.
Hemoglobin Mutation
The hemoglobin protein normally consists of four strands of around 140 amino acids each, the seventh of which in two of the strands is the compound glutamic acid, explain Drs. Campbell and Farrell. In sickle cell patients, the seventh amino acid in two of the strands is not glutamic acid but is instead a very different amino acid, called valine. Valine and glutamic acid have significant differences in their chemical structures and properties, meaning that the mutated strands act and are shaped differently, leading to mutant hemoglobin.
Expert Insight
While the mutation in the amino acid sequence that causes sickle cell anemia makes it harder for hemoglobin to form red blood cells and carry oxygen, it also makes it harder for the malaria pathogen to attack red blood cells. This, explain Drs. Garrett and Grisham, means that sickle cell anemia patients are less likely to get malaria than those individuals with normal hemoglobin, which is one reason that the genetic mutation may have persisted in the population for so long.
References
- National Heart Lung and Blood Institute: Sickle Cell Anemia
- "Biochemistry"; Mary Campbell, Ph.D. and Shawn Farrell, Ph.D.; 2005
- "Biochemistry"; Reginald Garrett, Ph.D. and Charles Grisham, Ph.D.; 2007
