Lecture 8.1: Haemoglobin and Myoglobin

Question 1

What do both Haemoglobin and Myoglobin do?

Answer 1

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

Question 2

Where is Myoglobin found?

Answer 2

Muscle Tissue

Question 3

Where is Haemoglobin found?

Answer 3

Red Blood Cells

Question 4

Function of Myoglobin

Answer 4

Myoglobin stores and facilitates diffusion of oxygen in the muscle

Has a high affinity for oxygen

Question 5

Function of Haemoglobin

Answer 5

Haemoglobin is responsible for the transport of oxygen throughout the body

Permits transfer of oxygen from haemoglobin in the blood to muscle myoglobin

Question 6

Haldane Effect

Answer 6

Haemoglobin gives up CO2 when pO2 rises (lungs) and binds CO2 when pO2 falls (tissues)

Question 7

Haem Structure

Answer 7

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)

Question 8

Oxygen binding to the Haem group in Haemoglobin and Myoglobin

Answer 8

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

Question 9

Features of Myoglobin Structure

Answer 9

• 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

Question 10

Binding of Oxygen by Myoglobin: Dissociation Curve

Answer 10

Oxygen binding to myoglobin shows a hyperbolic dependence on oxygen concentration- hyperbolic binding curve

Question 11

Binding of Oxygen by Haemoglobin: Dissociation Curve

Answer 11

Sigmoidal

Question 12

Features of Haemoglobin Structure

Answer 12

• 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

Question 13

What structural change does Haemoglobin undergo when binding oxygen?

Answer 13

Low Affinity T (Tense) State —> High Affinity R (Relaxed) State

Question 14

Why is the oxygen binding curve for haemoglobin sigmoidal?

Answer 14

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

Question 15

‘Cooperative’ binding of oxygen to haemoglobin

Answer 15

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

Question 16

Association and Dissociation

Answer 16

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

Question 17

Regulation of Oxygen Binding: 2-3 BPG

Answer 17

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

Question 18

Chronic Hypoxemia

Answer 18

Caused by pathological lung conditions or high altitude stimulates 2-3 BPG

Question 19

2-3 Biphosphoglycerate at high altitides

Answer 19

BPG concentration increases at high altitudes, promoting O2 release at the tissues

Question 20

Regulation of Oxygen Binding: Bohr Effect

Answer 20

• 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

Question 21

Carbon Monoxide Poisoning

Answer 21

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

Question 22

When is CO poisoning fatal?

Answer 22

Fatal when COHb is >50%