section 28.2
Functional Aspects of Hemoglobin
T y r a 1 4 0 (H C 2 ); r e s id u e
th a t lie s b e tw e e n h e lic e s
F a n d H in d e o x y -H b
P ro x im a l h is tid in e ; a 8 7 ( F 8 ;
b o n d e d to fifth p o s itio n
of th e h e m e g ro u p
O , b in d in g site
D istal h istid in e : a 5 8 (
lo c a te d n e a r (b u t n o t
a tta c h e d to ) s ix th p o s
o f th e h e m e iron
F IG U R E 2 8 -2
Secondary structure of the
chain of human hemoglobin. The helical regions (labeled A-H, after Kendrew), N and C
termini, and the histidines located near the heme group are indicated. The axes of the B and C helices are indicated by
dashed lines. Note that the
chain lacks helix D present in the /3 chain. The amino acid residues are numbered by two
different methods: from the N terminus of the polypeptide chain and from the N-terminal amino acid residue of each
helix. Nonhelical regions are designated by the letters of helices at each end of a region.
dissociable complex with oxygen.
Deoxyhemoglobin + 402 ^ oxyhemoglobin
This reaction goes to the right with an increase in oxygen
pressure (as in the lungs) and to the left with a decrease in
oxygen pressure (as in the tissues), in accordance with the
law of mass action. Table 28-1 shows typical partial pres-
sures of oxygen between the atmosphere and tissue mito-
chondria. Hemoglobin increases the solubility of oxygen
in the blood 70-fold (from 0.3 to 20.3 mL of oxygen per
milliliter of blood).
In Figure 28-4, the oxygen saturation percent for
hemoglobin is plotted against oxygen pressure in the
gas above the surface of the hemoglobin solution. The
curves, known as binding or dissociation curves, are often
characterized by their P
value, the oxygen pressure at
which the hemoglobin is 50% saturated with oxygen. For
comparison, the dissociation curve for myoglobin is also
shown. The hemoglobin curves are sigmoid (S-shaped),
whereas the myoglobin curve is a rectangular hyperbola.
This difference arises because hemoglobin is allosteric
and shows cooperative oxygen binding kinetics (Chap-
ter 7), whereas myoglobin is not allosteric. The binding
of each molecule of oxygen to hemoglobin causes bind-
ing of additional oxygen molecules. This cooperativity
occurs because hemoglobin is a tetramer. The coopera-
tive binding of oxygen by hemoglobin is the basis for
the regulation of oxygen and, indirectly, carbon dioxide
levels in the body. The molecular understanding of this
phenomenon is a major accomplishment of x-ray crys-
tallographic studies of protein structure. Myoglobin is a
heme protein found in high concentrations in red mus-
cle, particularly cardiac muscle, where it functions as a
storage site for oxygen. At the oxygen pressures found in
previous page 679 Bhagavan Medical Biochemistry 2001 read online next page 681 Bhagavan Medical Biochemistry 2001 read online Home Toggle text on/off