The Substitution of Valine for Glutamic Acid

Valine and glutamic acid are amino acids with very different structures and properties. They are both building blocks of protein, and sometimes mutations in your DNA can cause substitution of one for the other. This can potentially lead to serious disorders, the most well-known of which is called sickle cell anemia.

Amino acids have very similar structures up to a point, but each type of amino acid -- there are 20 common varieties -- has a unique side chain that determines its properties in proteins. Valine's side chain is made up entirely of carbon and hydrogen, while glutamic acid's side chain has oxygen in it as well, and is acidic. The major differences between valine and glutamic acid side chains mean they behave very differently in protein.

Substitution of one amino acid for another typically occurs as the result of a mutation to your DNA -- deoxyribonucleic acid -- which is the genetic material you inherit from your parents and have in each cell nucleus. DNA contains a "code" that the cells use to make proteins; if you receive mutated DNA from your parents, your DNA will contain misinformation, and the proteins you make from that section of DNA will be faulty, explains Dr. Lauralee Sherwood in her book "Human Physiology."

Some substitutions in proteins don't make much of a difference in terms of function -- this is most likely to be true when one amino acid is substituted with a very similar one -- but the substitution of valine for glutamic acid is very serious, because of their very different properties. Proteins are held into a three-dimensional shape that gives them their ability to function based upon interactions between amino acids. Glutamic acid has a negative charge that allows it to stick to positively charged amino acids, holding the protein's shape. Valine can't stick to positively charged amino acids, so a protein with this substitution won't be shaped correctly.

Sickle cell anemia is caused by the substitution of valine for glutamic acid. Chemist Linus Pauling first determined that it was the result of a mutation in the hemoglobin protein. Hemoglobin carries oxygen from your lungs to your tissues; if there's a mutation in the DNA that codes for the protein, it can't carry oxygen as effectively and results in misshapen red blood cells, explain Drs. Reginald Garrett and Charles Grisham in their book "Biochemistry."