468 Chapter 15 Enzyme RegulationThe

468 Chapter 15 Enzyme Regulation
The myoglobin polypeptide chain and the - and -chains of hemoglobin are com-
posed of 8 -helical segments denoted by the letters A through H. The short, un-
ordered regions that connect the helices are named for the segments they connect,
as in the AB region or the EF region. In an amino acid numbering system unique to
globin chains, successive residues in the helices are numbered, such as the histidine
at position 8 in the F helix, known as His F8.
The tetrameric nature of Hb is crucial to its biological function: When a molecule
of O2 binds to a heme in Hb, the heme Fe ion is drawn into the plane of the porphyrin ring.
This slight movement sets off a chain of conformational events that are transmitted to adja-
cent subunits, dramatically enhancing the affinity of their heme groups for O2. That is, the
binding of O2 to one heme of Hb makes it easier for the Hb molecule to bind ad-
ditional equivalents of O2. Hemoglobin is a marvelously constructed molecular ma-
chine. Let us dissect its mechanism, beginning with its monomeric counterpart, the
myoglobin molecule.
Myoglobin Is an Oxygen-Storage Protein
Myoglobin is the oxygen-storage protein of muscle. The muscles of diving mammals
such as seals and whales are especially rich in this protein, which serves as a store
for O2 during the animal’s prolonged periods underwater. Myoglobin is abundant
in skeletal and cardiac muscle of nondiving animals as well. Myoglobin is the cause
of the characteristic red color of muscle.
Venous
pO2
Myoglobin
0 20 40 60 80 100 120
Partial pressure of oxygen (pO2, torr)
100
80
60
40
20
Percent O2 saturation
Working
muscle
Resting
muscle
Hemoglobin
Arterial pO2
0
FIGURE 15.20 O2-binding curves for hemoglobin and
myoglobin.
Myoglobin (Mb)
Hemoglobin (Hb)
2
2 1
1
FIGURE 15.21 The myoglobin (pdb id  2MM1) and
hemoglobin (pdb id  2HHB) molecules.
Fe2+
–OOC
CH2
C
C
H3C
H
C
C C
C
COO–
H2C
CH2
C
CH3
C NH
HC
C N
C
C H2C C
C
C
HN C
C
C
C
N
C
H
HC
CH3 CH
CH2
CH3
C
C
H3C
H
C
C C
C
C
CH3
C N
HC
C N
C
C
C
C
N C
C
C
C
N
C
H
HC
CH3
CH3
CH2
H
–OOC
CH2
CH2
COO–
H2C
CH2
CH
CH2
H2C C
H
Protoporphyrin IX Heme
(Fe-protoporphyrin IX)
FIGURE 15.22 Heme is formed when protoporphyrin IX
binds Fe2.