revised April 10, 2002
An Overview of Hemoglobin
This brief overview of hemoglobin is not meant to be comprehensive. The
goal is to provide sufficient background to make this Web site useful to
people unfamiliar with the area. More detailed sources are listed at the
end of this file.
A.) What is hemoglobin?
Hemoglobin is a protein that is carried by red cells. It picks up oxygen
in the lungs and delivers it to the peripheral tissues to maintain the viability
of cells. Hemoglobin is made from two similar proteins that "stick
together". Both proteins must be present for the hemoglobin to pick
up and release oxygen normally. One of the component proteins is called
alpha, the other is beta. Before birth, the beta protein is not expressed.
A hemoglobin protein found only during fetal development, called gamma,
substitutes up until birth.
B.) How is hemoglobin made?
Like all proteins, the "blueprint" for hemoglobin exists in DNA
(the material that makes up genes). Normally, an individual has four genes
that code for the alpha protein, or alpha chain. Two other genes code for
the beta chain. (Two additional genes code for the gamma chain in the fetus).
The alpha chain and the beta chain are made in precisely equal amounts,
despite the differing number of genes. The protein chains join in developing
red blood cells, and remain together for the life of the red cell.
C.) How do abnormal hemoglobins arise?
The composition of hemoglobin is the same in all people. The genes that
code for hemoglobin are identical throughout the world. Occasionally, however,
one of the genes is altered by any of a variety of "accidents"
that can occur in nature. These alterations in the genes (called "mutations")
are very rare. Since genes are inherited, and they contain the information
needed to make a protein, if a mutation produces an abnormal hemoglobin
gene in a person, the gene will be passed on to his or her children. The children will produce a modified hemoglobin identical to that of the parent. Most
mutations in hemoglobin produce no problem. Occasionally, however, the alteration
in the protein changes aspects of its behavior. The types of disorders that
can result include sickle cell disease and thalassemia.
D.) What about all the different blood types?
Blood cells are made up of two components. The hemoglobin is in solution
inside the cell. The cell is surrounded by a membrane that holds in the hemoglobin. A rough analogy would be a rubber water balloon. The rubber would be
the membrane, and the water would be the hemoglobin. The blood types that
most of us know, A, B, O, and Rh, are properties of the membrane. The hemoglobin
inside the red cells of a person with type O blood and that inside the red
cells of a person with type A blood are identical. The analogy would be
of water balloons made from blue and red balloons. The color of the ballon
would differ, but the material inside (water) would be the same.
E.) How many types of abnormal hemoglobins are there?
Although the changes that produce abnormal hemoglobins are rare, several
hundred abnormal (or more precisely, "variant") hemoglobins exist.
These have accumulated over the millions of years of human existence. Most
variant hemoglobins function normally, and are only found through specialized research techniques. Some hemoglobins, however, do not function normally and can produce clinical disorders, such as sickle
cell disease.
F.) What happens if a hemoglobin gene "burns out"?
Genes can suffer damage to an extent that they no longer produce normal
amounts of hemoglobin. Usually, only one of the sets of hemoglobin genes
is affected, that is the alpha gene set or the beta gene set. For example,
one of the two beta globin genes may fail to produce a normal quantity of
beta chain protein. The alpha globin gene set will continue to produce a
normal quantity of alpha chain protein. An imbalance develops in the amount
of alpha chain and beta chain protein in the cell. There is too much alpha
chain for the amount of beta chain that is present. This imbalance is called
"thalassemia ". In this example, it
would be beta thalassemia, because it is the beta chain gene that has failed.
An analogy would be cars coming out of the factory. Engines and bodies must
be made in equal numbers to have functional automobiles. If the engine plant
goes on strike (thalassemia), the bodies produced by the body plant are
useless.
How can I find out more about hemoglobin disorders?
The best source of information about hemoglobin disorders in general are
textbooks of medicine. Textbooks of hematology tend to be very detailed,
and confusing for people not conversant with the area. Some text books of
medicine are:
- Harrison's Principles of Internal Medicine, McGraw-Hill
- The Principles and Practice of Medicine, Appleton, Century, Croftis
- "Hemoglobin: molecular, genetic, and clinical aspects", HF Bunn and B Forget, Saunders, 1986.