Hemoglobin
About 95 percent of the dry weight of the red cell
consists of hemoglobin, the substance necessary for
oxygen transport. Hemoglobin is a protein; a molecule
contains four polypeptide chains (a tetramer), each
chain consisting of more than 140 amino acids. To eachchain
is attached a chemical structure known as a heme group.
Heme is composed of a ringlike organic compound known
as a porphyrin to which an iron atom is attached. It
is the iron atom that reversibly binds oxygen as the
blood travels between the lungs and the tissues. There
are four iron atoms in each molecule of hemoglobin,
which, accordingly, can bind four atoms of oxygen. The
complex porphyrin and protein structure may be considered
to provide just the proper environment for the iron
atom so that it binds and releases oxygen appropriately
under physiological conditions. The affinity of hemoglobin
for oxygen is so great that at the oxygen pressure in
the lungs about 95 percent of the hemoglobin is saturated
with oxygen. As the oxygen tension falls, as it does
in the tissues, oxygen dissociates from hemoglobin and
is available to move by diffusion through the red cell
membrane and the plasma to sites where it is used. The
proportion of hemoglobin saturated with oxygen is not
directly proportional to the oxygen pressure. As the
oxygen pressure declines, hemoglobin gives up its oxygen
with disproportionate rapidity, so that the major fraction
of the oxygen can be released with a relatively small
drop in oxygen tension. The affinity of hemoglobin for
oxygen is primarily determined by the structure of hemoglobin,
but it is also influenced by other conditions within
the red cell, in particular the pH and certain organic
phosphate compounds produced during the chemical breakdown
of glucose, especially 2,3-diphosphoglycerate (see above
Functions).
Hemoglobin has a much higher affinity for carbon monoxide
than for oxygen. Carbon monoxide produces its lethal
effects by binding to hemoglobin and preventing oxygen
transport. The oxygen-carrying function of hemoglobin
can be disturbed in other ways. The iron of hemoglobin
is normally in the reduced or ferrous state, both in
oxyhemoglobin and deoxyhemoglobin. If the iron itself
becomes oxidized to the ferric state, hemoglobin is
changed to methemoglobin, a brown pigment incapable
of transporting oxygen. The red cells contain enzymes
capable of maintaining the iron in its normal state,
but under abnormal conditions large amounts of methemoglobin
may appear in the blood.
Discovery of the cause of sickle-cell anemia has led
to major advances in understanding of genetics, molecular
biology, and the mechanisms of disease. Sickle-cell
anemia is a serious and often fatal disease characterized
by an inherited abnormality of the hemoglobin. Personswho
have sickle-cell anemia are predominantly blacks. The
disease is caused by the mutationof a single gene that
determines the structure of the hemoglobin molecule.
Sickle hemoglobindiffers from normal hemoglobin in that
a single amino acid (glutamic acid) in one pair of the
polypeptide chains has been replaced by another (valine).
This single intramolecular change so alters the properties
of the hemoglobin molecule that anemia and other effects
are produced. The entire structure of the hemoglobin
molecule is known, and many other genetically determined
abnormalities have been identified. Some of these also
produce diseases of several types. Study of the effects
of altered structure of hemoglobin on its properties
has greatly broadened knowledge of the structure-function
relationships of the hemoglobin molecule. (For more
information about sickle-cell anemia, see blood diseases.)
