Protein Function - Oxygen Transport

Question 1

What is the role of myoglobin?

Answer 1

Pick up O2 from haemoglobin

Question 2

What is the structure of haem?

Answer 2

Protoporphyrin ring and an Fe atom bound to 4N atoms of the ring
Fe2+ can make 2 additional bonds to oxygen, one on either side of the plane

Question 3

Describe oxygen binding to the haem group

Answer 3

1 molecule of O2 binds to the haem group in myoglobin and haemoglobin
Fe atom is bound to the protein via a histidine residue on other side of ring

Question 4

Name features of myoglobin structure

Answer 4

Globular
153 aa
Compact
75% alpha-helical
One polypeptide chain

Question 5

What shape curve represents the binding of oxygen by myoglobin?

Answer 5

Hyperbolic

Rapid increase at first and quickly plateaus

Question 6

What shape is the oxygen dissociation curve for haemoglobin?

Answer 6

Sigmoidal

Affinity not constant

Question 7

What are the features of haemoglobin structure?

Answer 7

2 polypeptide chains in alpha2beta2 tetramer
Each chain contains essential haem prosthetic group
Conformation of each chain very similar to myoglobin

Question 8

What are the 2 states deoxyhaemoglobin can exist in?

Answer 8

Low affinity T state

High affinity R state

Question 9

How is the R state promoted?

Answer 9

Oxygen binding promotes stabilisation of the R state

Promotes more oxygen binding so haemoglobin has a higher affinity for oxygen

Question 10

What is cooperative binding?

Answer 10

Binding of one oxygen molecule promotes the binding of subsequent molecules
This means it is more sensitive to small differences in O2 concentrations

Question 11

Why would the T state alone not be beneficial?

Answer 11

Oxygen does not bind well as it has a low affinity

It therefore can’t carry much O2

Question 12

Why would the R state alone not be beneficial?

Answer 12

Oxygen binds tightly so the haemoglobin would not easily give up the oxygen

Question 13

What is the purpose of 2,3-bisphosphoglycerate (BPG)?

Answer 13

It lowers the affinity for O2 in haemoglobin
Present in RBC at ~5mM
1 BPG binds per haemoglobin tetramer
BPG concentration increases at high altitudes, promoting O2 release at the tissues

Question 14

What is the Bohr effect?

Answer 14

Binding of H+ and CO2 lowers affinity of haemoglobin for oxygen
It ensures the delivery of oxygen is coupled to demand

Question 15

Why is the Bohr effect not exhibited in myoglobin?

Answer 15

Myoglobin only consists of a single polypeptide chain

Question 16

Describe what happens in carbon monoxide poisoning and how to treat it

Answer 16

It combines very tightly with ferromyoglobin and ferrohaemoglobin and blocks oxygen transport
CO binds to haemoglobin more readily than oxygen
Treat with blood transfusion or a hyperbaric chambers

Question 17

What are the 3 normal adult haemoglobins?

Answer 17

HbA alpha2beta2 (90%)
HbF alpha2gamma2
HbA2 alpha2delta2

Question 18

What is the major haemoglobin in fetal blood and how is it different?

Answer 18

HbF
Higher binding affinity for oxygen than HbA (maternal blood), allows transfer of oxygen to fetal blood supply from mother

Question 19

What occurs in sickle cell anaemia?

Answer 19

Mutation of glutamate (hydrophilic) to valine (hydrophobic) in beta globin (missense mutation)
Haemoglobin molecules combine to bury hydrophobic valines
Long chains of haemoglobin forms (sickled cells)
These cells more prone to lyse

Question 20

What are thalassaemias?

Answer 20

Group of genetic disorders where there is an imbalance between number of alpha and beta globin chains