close

Вход

Забыли?

вход по аккаунту

?

Biochemistry 6/e

код для вставкиСкачать
Biochemistry
Sixth Edition
Berg • Tymoczko • Stryer
Chapter 7:
Hemoglobin:
Portrait of a Protein in Action
Copyright В© 2007 by W. H. Freeman and Company
Erythrocytes
(Red cells)
Hemoglobin and Myoglobin
• These are conjugated proteins. A simple
protein has only a polypeptide chain. A
conjugated protein has a non-protein part in
addition to a polypeptide component. Both
myoglobin and hemoglobin contain heme.
• Myoglobin 17000 daltons (monomeric)
153 amino acids
• Hemoglobin - 64500 daltons ( tetrameric)
a-chain has 141 amino acids
b-chain has 146 amino acids
Hemoglobin O2 carrying capability
• Erythrocytes/ml blood: 5 billion
• Hemoglobin/red cell:
( 5 x 109 )
280 million ( 2.8 x 108 )
• O2 molecules/hemoglobin: 4
• O2 ml blood: (5 x 109)(2.8 x 108)(4) = (5.6 x 1018)
or (5.6 x 1020) molecules of O2/100 ml blood
A single subunit of Hemoglobin,
an a2b2 tetramer
Myoglobin, monomeric
3o structure overlap:
myoglobin, a-globin and b-globin
a-Globin (blue)
b-Globin (violet)
Myoglobin (green)
Aromatic Heme
Iron in Hemoglobin binding O2
Iron in Myoglobin binding O2
Resonance in Iron binding O2
Hemoglobin, a2b2 tetramer
O2 binding: Hemoglobin & Myoglobin
P50 = 2 torr
P50 = 26 torr
O2 transport capability, a comparison
Resting state vs exercise
O2 Binding Changes 4o Structure
Allosteric Proteins
• There are two limiting models of allosterism:
•Monod, Wyman & Changeux:
Two State, concerted
•Koshland, Nemethy & Filmer:
One State, sequential
• Allosteric effectors (modulators) bind to a protein
at a site separate from the functional binding site
(modulators may be activators or inhibitors)
• Oxygen binding and release from Hb are
regulated by allosteric interactions
• Hemoglobin cooperativity behaves as a mix of
the above two models.
Concerted, two state model
Monod, Wyman & Changeux
R-state vs T-state Binding
Sequential, one state model
Koshland, Nemethy & Filmer
Decreasing O2 affinity
2,3-bisphosphoglycerate
(2,3-BPG)
• Lowers the
affinity of oxygen
for Hemoglobin
2,3-bisphosphoglycerate (2,3-BPG)
The binding pocket for BPG contains 4 His and 2 Lys
Binding of bisphosphoglycerate
The Bohr Effect
Bohr Effect:
• Lowering the
pH decreases
the affinity of
oxygen for Hb
Loss of O2 from Hemoglobin
Carbamate:
• CO2 combines
with NH2 at the
N-terminus of
globins
Carbamate formation
Covalent binding at the N-terminus of each subunit
Combined
Effects
CO2 , BPG and pH
are all allosteric
effectors of
hemoglobin.
CO2 & Acid from Muscle
CO2 & Hemoglobin Blood Buffering
Metabolic oxidation in cells uses oxygen and
produces CO2 .
The pO2 drops to ~20 torr and oxygen is released
from incoming HbO2-.
HbO2- <===> Hb- + O2
Release is facilitated by CO2 reacting with the Nterminus of each hemoglobin subunit, by
non-covalent binding of BPG and the Bohr
effect.
Events at Cell sites
The localized increase in CO2 results in
formation of carbonic acid which ionizes
to give bicarbonate and H+.
CO2 + HOH <===> H2CO3
carbonic anhydrase
H2CO3 <===> HCO3- + H+
pKa = 6.3
The increase in [H+] promotes protonation of Hb-.
HHb <===> Hb- + H+
pKa = 8.2
Events at Cell sites
The predominant species in this equilibrium at
pH 7.2 is HHb.
So, O2 remains at the cell site, HHb carries a
proton back to the lungs and bicarbonate
carries CO2 .
Charge stability of the erythrocyte is maintained
via a chloride shift, Cl- <==> HCO3- .
Events at Lung sites
Breathing air into the lungs increases the partial
pressure of O2 to ~100 torr.
This results in O2 uptake by HHb to form HHbO2.
HHb + O2 <===> HHbO2
Ionization of HHbO2 then occurs and HbO2carries O2 away from the lungs.
HHbO2 <===> HbO2- + H+
pKa = 6.6
So, the predominant species at pH (7.4) is HbO2-.
Events at Lung sites
The localized increase in [H+] from hemoglobin
ionization serves to protonate HCO3- .
H2CO3 <===> HCO3- + H+
pKa = 6.3
H2CO3 <===> CO2 + HOH
carbonic anhydrase
The resulting H2CO3 decomposes in presence of
carbonic anhydrase and CO2 is released in the
lungs.
Charge stability of the erythrocyte is maintained
again via a chloride shift, HCO3- <==> Cl-.
Sickle Cell due to Glu 6 пѓ Val 6
Binding relationships
The binding of O2 to myoglobin can be shown by the
equilibriuim:
Mb + O2 <===> MbO2
(1)
The dissociation constant for the loss of O2 is:
[Mb][O2]
Keq = KD = -------------(2)
[MbO2]
Define the fraction of sites, Y, occupied by O2 as:
[MbO2]
sites bound
Y = --------------------- = ----------------- (3)
[Mb] + [MbO2]
total sites
Binding relationships
Substituting from equation (2) into (3):
[MbO2]
1
Y = ---------------------------= -----------K [MbO2]
K
---------- + [MbO2]
---- + 1
O2
O2
or:
[O2]
pO2
pO2
Y = ---------- = ----------- = -----------K + O2
K + pO2 p50 + pO2
Evaluating K at Y = 0.5 gives K = p50 for O2
Biochemistry
Sixth Edition
Berg • Tymoczko • Stryer
End of Chapter 7
Copyright В© 2007 by W. H. Freeman and Company
Документ
Категория
Презентации
Просмотров
13
Размер файла
4 214 Кб
Теги
1/--страниц
Пожаловаться на содержимое документа