Session 10-Protein Function-Hb And Myoglobin

Question 1

What does the Haem group consist of?

Answer 1

Protoporphyrin ring and Fe atom bound to four N atoms of the ring, Fe2+ can make two additional bonds to O2, one on either side of the plane

Question 2

How is the Fe atom bound to the protein?

Answer 2

Via a histidine residue (proximal histidine) on the other side of the ring

Question 3

What are three features of the myoglobin structure?

Answer 3

1. 153 AA
2. Compact
3. 75% alpha-helical

Question 4

Binding of O2 to myoglobin shows what kind of dependence on O2 concentration?

Answer 4

Hyperbolic

Question 5

What is the shape of the Hb oxygen dissociation curve?

Answer 5

Sigmoidal

Question 6

What is the structure of Hb? (3)

Answer 6

1. Four polypeptide chains: alpha chain (141 AA), beta chain (146 AA) in alpha2 beta2 tetramer
2. Each chain contains essential haem prosthetic group
3. Conformation of polypeptide chain very similar to that of myoglobin

Question 7

True or false: Hb undergoes structural change on binding to O2

Answer 7

TRUE

Question 8

What are the two states in which deoxyhaemoglobin can exist?

Answer 8

1. Low affinity T state (tense state)

2. High affinity R state (relaxed state)

Question 9

Oxygen binding to Hb promotes the stabilisation of which state?

Answer 9

R state - AA residues change conformation and Hb molecule changes to the high affinity state

Question 10

Why is the O2 binding curve sigmoidal for Hb?

Answer 10

Cooperative binding of O2 (cooperativity):
Binding affinity for O2 increases as more O2 molecules bind to Hb subunits
Binding of first O2 molecule to the first subunit is hard (low affinity)
Binding of the last O2 molecule to the fourth subunit is easy (high affinity)

Question 11

What is an allosteric effect?

Answer 11

Binding of a ligand to a site on a protein molecule in such a way that the properties of another site on the same protein are affected

Question 12

Define allosteric

Answer 12

Alteration of the activity of an enzyme by means of a conformational change induced by a different molecule

Question 13

How is oxygen binding regulated?

Answer 13

2,3-bisphosphoglycerate (BPG)

Question 14

What does BPG do?

Answer 14

Changes the affinity of Hb for O2

Question 15

How much BPG is present in RBCs?

Answer 15

~5mM

Question 16

Complete the sentence:

BPG concentration increases at ____ altitudes, promoting O2 _______ at tissues. Hb therefore has a ______ affinity for O2 as the curve shifts to the ____

Answer 16

High
Release
Lower
Right

Question 17

What does the binding of H+ and CO2 to Hb do?

Answer 17

Lowers the affinity of Hb for O2

Question 18

What is the Bohr effect?

Answer 18

Ensures delivery of O2 coupled to demand

Question 19

Why is CO poisonous?

Answer 19

Combines with ferromyoglobin and ferrohaemoglobin and blocks O2 transport

Question 20

What does partial CO binding do?

Answer 20

Increases affinity for O2 for unaffected subunits

Question 21

Does HbF (foetal Hb) have a higher or lower affinity for O2 than HbA?

Answer 21

Higher, allows the transfer of O2 to foetal blood supply from the mother

Question 22

Sickle cell anaemia is the mutation of what?

Answer 22

Glutamate to valine in beta-globin

Question 23

What are thalassaemias?

Answer 23

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

Question 24

What happens in beta-thalassaemia?

Answer 24

Decreased or absent beta-globin chain production

Alpha-chains are unable to form stable tetramers

Question 25

What happens in alpha-thalassaemia?

Answer 25

Decreased or absent alpha-globin chain production

Beta-chains can form stable tetramers with increased affinity for O2