Heme proteins:

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Heme proteins structure and function
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P50 2.8 torr
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Fraction of Mb bound to O2 at pO2 30 torr
pO2 in capillaries
P50 2.8 torr
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Figure 8-42a The X-Ray structure of horse heart
cytochrome.
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myoglobin single subunit
hemoglobin four homologous subunits two alpha
two beta chains
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Table 10-1a The Amino Acid Sequences of the a and
b Chains of Human Hemoglobin and of Human
Myoglobina,b
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Table 10-1b The Amino Acid Sequences of the a and
b Chains of Human Hemoglobin and of Human
Myoglobina,b
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Figure 10-3 Oxygen dissociation curves of Mb and
of Hb in whole blood.
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Non-cooperative binding
Cooperative binding
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About 33 of O2 delivered
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About 42 of O2 delivered
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Figure 10-5 A picket-fence Fe(II)porphyrin
complex with bound O2.
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Figure 10-7 Comparison of the O2-dissociation
curves of stripped Hb and whole blood in 0.01M
NaCl at pH 7.0.
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Figure 10-13a The X-ray structure of deoxyHb as
viewed down its exact 2-fold axes.
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Figure 10-13b The X-ray structure of oxyHb as
viewed down its exact 2-fold axes.
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Oxy-Hb R State
Deoxy-Hb T State
VVP Fig 7-5
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Figure 10-14 The major structural differences
between the quaternary conformations of (a)
deoxyHb and (b) oxyHb.
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Figure 10-15 The heme group and its environment
in the unliganded a chain of human Hb.
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Figure 10-16 Triggering mechanism for the T R
transition in Hb.
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Figure 10-17 The a1Cb2FG interface of Hb in (a)
the T state and (b) the R state.
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Figure 10-18 The hemoglobin a1b2 interface as
viewed perpendicularly to Fig. 10-13.
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Figure 10-7 Comparison of the O2-dissociation
curves of stripped Hb and whole blood in 0.01M
NaCl at pH 7.0.
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Binding and Release of O2, BPG, CO2, H
Lungs
Capillaries
CO2
Respiring cells
Mitochondrion(O2) Mb
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Figure 10-22 Binding of BPG to deoxyHb.
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Figure 10-8 The effects of BPG and CO2, both
separately and combined, on hemoglobins
O2-dissociation curve compared with that of whole
blood (red curve).
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Figure 10-6 Effect of pH on the O2-dissociation
curve of Hb the Bohr effect.
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b H146 is deprotonated in the R state
b H146
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The R to T transition brings b D94 close to b
H146. How does this affect pKa for b H146?
b H146
b D94
NH
CO
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How does this affect pKa for b H146? pKa for b
H146 increases, the protonated state is now
favored.
b H146
b D94
NH
CO
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Tissue
Lungs
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Figure 10-9 The effect of high-altitude exposure
on the p50 and the BPG concentration of blood in
sea leveladapted individuals. Adaptation to
high altitude increased BPG
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Figure 10-10 The O2-dissociation curves of blood
adapted to sea level (black curve) and to high
altitude (red curve).
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Normal Red Blood Cells
Sickled Red Blood Cells
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Normal Red Blood Cells have a flattened discoid
shape rather than a spherical shape
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
vs.
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
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Figure 7-20 A map indicating the regions of the
world where malaria caused by P. falciparum was
prevalent before 1930.
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Hb A)
Normal hemoglobin (
deoxyhemoglobin
Oxy Hb A
T state
R state
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Sickle Hemoglobin (Hb S)
See VVP Fig 7-17
b E6V mutation on surface of Hb causes
aggregation of deoxy Hb
deoxy Hb S
Oxy Hb S
forms polymeric rods
in T state
R state
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Figure 10-24 Electron micrograph of deoxyHbS
fibers spilling out of a ruptured erythrocyte.
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Figure 10-25a 220-Å in diameter fibers of
deoxyHbS.(a) An electron micrograph of a
negatively stained fiber.
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Figure 10-25b 220-Å in diameter fibers of
deoxyHbS.(b) A model, viewed in cross section,
of the HbS fiber.
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Figure 10-26a Structure of the deoxyHbS fiber.
(a) The arrangement of the deoxyHbS molecules in
the fiber.
b A schematic diagram indicating the
intermolecular contacts in the crystal structure
of deoxyHbS.
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Figure 10-26c Structure of the deoxyHbS fiber.
(c) The mutant Val 6b2 fits neatly into a
hydrophobic pocket formed mainly by Phe 85 and
Leu 88 of an adjacent b1 subunit.
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Figure 10-33 Models of ligand binding.
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Figure 10-29 The species and reactions permitted
under the symmetry model of allosterism.
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Figure 10-31 Heterotropic interactions in the
symmetry model of allosterism.
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Figure 10-34 The sequential model of allosterism.
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Figure 10-35 Sequential binding of ligand in the
sequential model of allosterism.
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Figure 10-36 The sequential and the symmetry
models of allosterism can provide equally good
fits to the measured O2-dissociation curve of Hb.
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