CHAPTER
Hemoglobin
The easy availability of blood has resulted in many studies
of its constituents. Probably the most extensively studied
component is hemoglobin, the predominant protein in the
red blood cell and the molecule responsible for transport-
ing oxygen, carbon dioxide, and protons between the lungs
and tissues. The study of hemoglobin has led to a detailed
knowledge of how oxygen and carbon dioxide transport is
accomplished and regulated and has provided insight into
the functioning of other allosteric proteins (Chapter 7).
Hemoglobin is the first allosteric protein for which molec-
ular details of allosteric effector binding and the mecha-
nism of allosteric action are known. Studies of the genes
coding for the globin polypeptide chains have provided
a better understanding of many anemias and of the regu-
lation of expression of other eukaryotic genes. Correc-
tion of the genetic defects in sickle cell anemia and tha-
lassemia by the introduction of new genetic information
into bone marrow cells (gene therapy) is being actively
explored.
28.1
Structure of Hemoglobins
Globin Chains
Mammalian hemoglobins are tetramers made up of two
a-Iike subunits (usually
a)
and two non-a subunits (usu-
ally /0,
y,
or
S).
These subunits differ in primary struc-
ture but have similar secondary and tertiary structures.
However, the differences in tertiary structure among them
are critical to the functional properties of each subunit.
Each globin subunit has associated with it, by noncova-
lent interaction, an Fe2+-porphyrin complex known as a
heme group.
Oxygen binding occurs at the heme iron. The
predominant hemoglobin in adult erythrocytes is a
2
/32,
known as hemoglobin Ai (HbA). The structural and func-
tional characteristics of hemoglobin have been worked out
almost entirely through studies of HbA and its naturally
occurring variants.
Each tetramer has a molecular weight of about 64,500,
and each a-Iike and /3-like chain has a molecular weight
of about 15,750 and 16,500, respectively. The subunits
are situated at the comers of a tetrahedron (Figure 28-1).
The structure changes slightly during the binding and re-
lease of oxygen. In a tetramer, dissimilar chains are more
strongly joined than similar chains. In dilute solution, oxy-
hemoglobin dissociates as follows:
There is no evidence for the formation of © © or ®@,
although in the absence of a-chains /3
4
(HbH) forms.
Association involves salt bridges, hydrogen bonds, van
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