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Hemoglobin: Portrait of a Protein
in Action
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7.3 H+ions and CO2Promote the Release of Oxygen:
The Bohr Effect
Rapidly metabolizing tissuesgeneral largeamounts of H+and CO2.
To release O2where the need is greatest,
hemoglobin has evolved to respond to higherlevels of these substance. H+and CO2are
allosteric effectors of hemoglobin
The regulation of O2binding by H+
and CO2iscall Bohr effect (1904)
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The oxygen affinity of Hemoglobinas pH (7.47.2): tendency to
release oxygen increases
For example: Transport The lungs (pH 7.4, 100 torr)Active muscle (pH
7.2, 20 torr):
Result: in a release of oxygen 66% (pH 7.4)
77% (pH 7.2)
At least two sets of chemical groups are important for sensing changes in
pH:
-amino groups of a chain N-term
side chains (His) of b146 and a122
pKavalues near 7
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CO2stimulates oxygen release by two mechanisms
First, high concentrate of CO2leads to a drop in pH within red blood cell
(RBC)
Second, direct chemical interaction between CO2
and Hb stimulates
oxygen release
carbonic anhydrase
CO2decrease the affinity of Hbfor oxygen
H2CO3: pKa 3.5
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CO2stabilizes deoxyHb by reacting with the terminal amino groupto form carbamate group (- charged)terminal amino group lie at the interface between the ab
dimerssalt bridge stabilizes the T state (favoring the release of O2)a mechanism of CO2transport (~14%)
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CO2released from RBC lung (in the form of HCO3-)
exchange of HCO3-and Cl-through antiporter
Figure: transport of CO2from tissues to lungs. Most carbondioxide is transported to the lungs in the form of HCO3
- produced
in red blood cells and then release into the plasma. A lesser
amount is transport bay hemoglobin in the form of an attached
carbamate
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Examination of the structure of hemoglobin S reveals that the
new valine residue lies on the surface of the T-state molecule.
Why do these aggregates not form when HbS isoxygenated?
: oxyHb in R state Phe 85, Leu88 on bchain are largelyburied inside the Hb assembly
decreased the solubility of deoxy
Hb
: Val6-Phe85, Lue88aggregationHbS fiber is formed from 14 chains
of multiple interlinked Hbs
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The accumulation of free alpha-hemoglobin chain isprevented
AHSP: -hemoglobin stabilizing protein, in RBCs The ASHP binds to the chain monomers and
creates a highly soluble complex; does notprecipitate
AHSP:
- It can bind to both the oxygenated and deoxygenatedforms of the alpha chain
- Binds to the alpha chain as it is being produced-It is displaced when beta-hemoglobin is produced
-Prevents accumulation of free alpha hemoglobin
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Additional globin are encoded in the human
genome
In additional to the gene for myoglobin, the two
gens for -hemoglobin, and the one for -hemoglobin, the human haploid genomecontain other globin genes.
Examination of the human genome sequencehas revealed two additional globins:neuroglobin, cytoglobin
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Question
1. The amount of oxygen released by thehemoglobin molecules in the blood to thetissues
a. decreases as temperature increases
b. increases as blood pH decreases(acidityincreases)
c. decreases as pCO2increases
d. increases as pCO2decreases
B
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2. Most carbon dioxide is transported as
__________ in the blood.
bicarbonate ions
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3. Which of these factors increases respiratoryrate (increases release O2)?
A)increased blood pCO2
B)increased blood pH
C)increased blood pO2D)all of these
A
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4. What do the three amino acids in deoxyhemoglobin form inorder to stabilize the T state quaternary structure?
salt bridges
5. How does carbon dioxide form carbamate?
by reacting with the terminal amino group
6. What is the reason thalassemia occurs?
by an imbalanced production of hemoglobin chains