Lecture 8.1: Haemoglobin and Myoglobin Flashcards
What do both Haemoglobin and Myoglobin do?
Haemoglobin and myoglobin bind and transport molecular oxygen
Poorly diffusible: in a multicellular organism O2 will not reach the target tissues by diffusion alone
Globin has evolved to transport molecular oxygen
Where is Myoglobin found?
Muscle Tissue
Where is Haemoglobin found?
Red Blood Cells
Function of Myoglobin
Myoglobin stores and facilitates diffusion of oxygen in the muscle
Has a high affinity for oxygen
Function of Haemoglobin
Haemoglobin is responsible for the transport of oxygen throughout the body
Permits transfer of oxygen from haemoglobin in the blood to muscle myoglobin
Haldane Effect
Haemoglobin gives up CO2 when pO2 rises (lungs) and binds CO2 when pO2 falls (tissues)
Haem Structure
Haem consists of a porphyrin ring and an Fe2+ atom bound to 4 N atoms of the ring
Fe2+ can make bonds to oxygen on either side of the plane (though only one at a time)
Oxygen binding to the Haem group in Haemoglobin and Myoglobin
1 molecule of O2 binds to the haem group in myoglobin and haemoglobin
Fe atom is bound to the protein via a histidine residue (proximal histidine) on the other side of the ring
Features of Myoglobin Structure
• 153 aa, compact, tightly folded
• 75% α-helical (8 helices)
• His 93 in the 8th α-helix is covalently linked to Fe
• Haem is linked into the Fe helix by the proximal and distal histidine
Binding of Oxygen by Myoglobin: Dissociation Curve
Oxygen binding to myoglobin shows a hyperbolic dependence on oxygen concentration- hyperbolic binding curve
Binding of Oxygen by Haemoglobin: Dissociation Curve
Sigmoidal
Features of Haemoglobin Structure
• α2β2 tetramer
• 2 polypeptide chains: α (141 aa), β (146 aa)
• Each chain contains an essential haem prosthetic group, binds an O2
• Conformation of each polypeptide chain is very similar to that of
myoglobin, similar amino acids
What structural change does Haemoglobin undergo when binding oxygen?
Low Affinity T (Tense) State —> High Affinity R (Relaxed) State
Why is the oxygen binding curve for haemoglobin sigmoidal?
Cooperative binding of oxygen
Binding affinity for oxygen increases as more oxygen molecules bind to Hb subunits
Binding of 1st O2 molecule to 1 subunit is hard – low affinity
Binding of last O2 molecule to 4th subunit is very easy – high affinity
‘Cooperative’ binding of oxygen to haemoglobin
The binding of one oxygen molecule promotes the binding of subsequent molecules
The sigmoidal binding curve of haemoglobin means that O2 can be efficiently carried from the lungs to the tissues
More sensitive to small difference in O2 concentrations
Association and Dissociation
In lungs, alveolus has mixed venous blood pO2 of 40 mmHg/ O2 saturation of ~75%
Cooperative nature of O2 binding to Hb means single unoccupied heme groups have high affinity for O2
Allows the capture of maximal O2 as it diffuses across the blood-gas interface
Regulation of Oxygen Binding: 2-3 BPG
2-3 Biphosphoglycerate decreases haemoglobin’s oxygen affinity
Shifts the haemoglobin oxygen curve to the right, thus increasing tissue accessibility to oxygen
1 BPG binds per haemoglobin tetramer and decreases the affinity for O2
Chronic Hypoxemia
Caused by pathological lung conditions or high altitude stimulates 2-3 BPG
2-3 Biphosphoglycerate at high altitides
BPG concentration increases at high altitudes, promoting O2 release at the tissues
Regulation of Oxygen Binding: Bohr Effect
• H+ and CO2 both bind to haemoglobin molecules
• Binding of H+ and CO2 lowers the affinity of haemoglobin for O2
• Metabolically active tissues produce large amounts of H+ and CO2
(HCO3-)
• H+ facilitates O2 unloading by shifting the dissociation curve to the right
increasing CO2 carrying capacity
• The Bohr effect ensures the delivery of O2 is coupled to demand
Carbon Monoxide Poisoning
Carbon monoxide (CO) is a poison because it combines with ferromyoglobin and ferrohaemoglobin and blocks oxygen transport
CO binds to haemoglobin 250x more readily than O2
CO binding also acts to increase the affinity for oxygen for unaffected subunits
When is CO poisoning fatal?
Fatal when COHb is >50%
