liveonearth (liveonearth) wrote,

  • Location:
  • Mood:
  • Music:

Biochemistry 203: Vampirism, Hemoglobin and Thalassemia

Vampirism as a myth may be based in the very real biochemistry of blood. A quick primer. We have hemoglobin in our blood, it is the stuff in red blood cells that carries the oxygen from the lungs to the tissues, and it also brings acids from the tissues to the lungs where acid is breathed off as carbon dioxide.

Hemoglobin is a tetramer of four globins, which are individual proteins that have in this case become associated and cooperative. The first globin was myoglobin, which is the protein that stores oxygen in our muscles until it is needed. In modern critters hemoglobin is found inside red blood cells, and circulates in the blood. Hemoglobin picks up oxygen at the lungs and hands it over when it happens to circulate by and the myoglobin demands it. All the other globins appear to have evolved from myoglobin, based on how much they differ at the polypeptide level. Globins are designated by the Greek alphabet (alpha, beta, gamma, delta, epsilon and zeta globins). Alpha and beta are also split into 1 and 2, and associate with each other as dimers--they hang around in pairs. Normal human adult hemoglobins incorporate 2 pairs each of either alpha 1 beta 2 or alpha 2 beta 1 globins.

But if you have THALASSEMIA then one or more of your genes coding for globins is messed up. The genes could just be deleted, or they could have a nonsense mutation, or another gene product could do post-translational modification to the globins that causes them to not work right.

A normal human has four different gene copies coding for each globin. We have four copies of each adult globin (alpha and beta) as well as an assortment of other globin coding genes that were used during the embryonic, fetal and birth-early infancy stages of life. Those genes get turned off when the regular adult genes kick in--but will turn back on if the adult genes don't work. It's amazing all the ways that the body can try to cope with a missing gene product. Hemoglobin is always made of four globins, but substitutions of all kinds can create tetramers that function, if not at the normal level, for the purpose of oxygen transport.

The severity of thalassemia is directly related to how many genes coding for globins are nonfunctional. If you have three functioning gene copies of alpha 1, you'll probably make enough to not notice your mild anemia. But if you have only one working gene for the globin you need, you may feel the stress. And if you have none, your body has to get creative to keep you alive.

Beta thalassemia is the condition of missing your beta globin coding genes. The body copes by expressing the gamma globin gene, which usually turns off at birth. Apparently individuals with this condition show consistent signs and symptoms. They are sensitive to light, have "lantern jaw" (mandibular prominence) and crave red meat and blood--things with fresh hemoglobin in them. Let me see your neck. I think I am going to bite you.

The genes that code for alpha 1 and alpha 2 are adjacent in the DNA. They are different by only one amino acid, and can replace each other in the alpha-beta dimers without causing big trouble. If a person has no working alpha globin genes, the body can make tetramers of beta. There is also a gamma tetramer, known as Bart's anemia or Hb Bart's, which would be necessary if you lacked alpha and beta globin coding genes.

Hemoglobins made of less than optimal compenents are low functioning because they don't change shape when the first oxygen binds or unbinds--don't have the binding advantage of the chemical cooperativity of normal hemoglobin subunits. Also the Bohr effect doesn't work on them so they don't unload oxygen at the tissues as effectively.

More, on sickle cell anemia and more, to come.
Tags: biochemistry, blood, genetics, hemoglobin, thalassemia

  • Post a new comment


    Comments allowed for friends only

    Anonymous comments are disabled in this journal

    default userpic

    Your reply will be screened

    Your IP address will be recorded