section 28.2

Functional Aspects of Hemoglobin

647

HOOC

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

H E M E G R O 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

a

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

a

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

50

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