SESSION 10

Question 1

What are the features of myoglobin structure?

Answer 1

• single polypeptide chain
• compact
• 75% alpha helix
• binds to only one oxygen

Question 2

Describe the binding of oxygen to myoglobin

Answer 2

In deoxymyoglobin, iron is slightly below the plane of the ring
Oxygen binding causes movement of iron into plane of the ring

Oxygen binding to myoglobin shows a hyperbolic dependence on oxygen concentration

Myoglobin has a higher affinity for oxygen than haemoglobin, therefore it is more likely to bind to oxygen but less likely to unload

Question 3

What are the features of haemoglobin?

Answer 3

• 2 polypeptide alpha chains
• 2 polypeptide beta chains
• contains an essential haem prosthetic group

Question 4

Describe the structural change that haemoglobin undergoes when binding to oxygen

Answer 4

Deoxyhaemoglobin can exist in low affinity T state or high affinity R state

Oxygen binding promotes stabilisation of the R state

Thus oxygen binding promotes a change in haemoglobin conformation

Question 5

Why is the oxygen binding curve for haemoglobin sigmoidal?

Answer 5

Cooperative binding or oxygen- binding affinity for oxygen increases as more oxygen molecules bind to haemoglobin subunits

The binding of one oxygen molecule promotes the binding of subsequent molecules

• binding of 1st oxygen molecule to one subunit is hard - low affinity
• binding of last oxygen molecule to 4th subunit is very easy- high affinity

The sigmoidal binding curve of haemoglobin means that oxygen can be efficiently carried from the lungs to the tissue

Shift to the right- lowers oxygen affinity
Shift to the left- increases oxygen affinity

Question 6

Describe how 2,3 - bisphosphoglycerate regulates oxygen binding

Answer 6

• present in red blood cells
• 1 BPG binds per haemoglobin tetramer and decreases the affinity for oxygen
• BPG concentration increases at high altitudes, promoting oxygen release at the tissues

Question 7

Describe how CO2 and H+ regulates oxygen binding

Answer 7

• CO2 and H+ can both bind to haemoglobin molecules
• Binding of CO2 and H+ lowers the affinity of haemoglobin for oxygen -> BOHR EFFECT
• Metabolically active tissues produce large amount of CO2 and H+
• The Bohr effect ensures the delivery of oxygen is coupled to demand

Question 8

Describe how carbon monoxide poisoning regulates oxygen binding

Answer 8

• 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
• increase partial pressure of oxygen
• fatal when COHb is > 50%
• CO binding also acts to increase the affinity for oxygen for unaffected subunits

Question 9

What is the importance if foetal haemoglobin?

Answer 9

HbF is the major haemoglobin in foetal blood

Higher binding affinity for oxygen than HbA which allows transfer of oxygen to foetal blood supply from the mother

Question 10

Describe sickle cell anaemia

Answer 10

• single base mutation -> glutamate to valine in B globin (HbS)
• sticky hydrophobic pocket formed by Val allows deoxygenated HbS to polymerise
• worse in the T state as they are present on the surface= hydrophobic- don’t want to interact
• sickles cells are more prone to lysis

Question 11

Describe both B thalassamias and a- thalassamias

Answer 11

B- thalassamias:

• decreased or absent B- globin chain production
• A- chains unable to form stable tetramers
• symptoms appear after birth

A- thalassamias:

• decreased or absent a- globin chain production
• several different levels of severity sue to the multiple copies of the a- chains present
• B- chains can form stable tetramers with increased affinity for oxygen onset before birth

Question 12

What are the ideal characteristic for an effective transporter?

Answer 12

Enough oxygen needs to be picked up in the lungs and released into the tissues

Question 13

State the properties of allosteric enzymes and their electors

Answer 13

Allosteric enzymes usually consist of more than 1 subunit
Allosteric enzymes do not show Michaelis- Menten kinetics
Allosteric enzymes are not regulated primarily by covalent modification
Allosteric effectors may either inhibit or activate an enzyme
Allosteric effectors bind to an effector molecule rather than the active site on a target enzyme

Question 14

Is ATP an allosteric inhibitor or activator?

Answer 14

Inhibitor:

Stabilises the T state; higher amounts of ATP means that glycolysis is not required

Question 15

Is AMP an allosteric inhibitor or activator?

Answer 15

Activator:

Stabilises the R state; higher amounts of AMP means that glycolysis is required as there is a lack of ATP

Question 16

Is Citrate an allosteric inhibitor or activator?

Answer 16

Inhibitor:
Stabilises the T state; higher amounts of ATP means the glycolysis is not required as higher metabolism has resulted in citrate accumulation

Question 17

Is Fructose- 2, 6- bisphosphate an allosteric inhibitor or activator?

Answer 17

Activator;

Stabilises the R state; higher amounts of AMP means hat glycolysis is required

Question 18

Is H+ an allosteric inhibitor or activator?

Answer 18

Inhibitor;
Stabilises the T state; higher amounts of ATP means that glycolysis is not required as higher metabolism has resulted in H+ accumulation

Question 19

Define warfarin

Answer 19

Warfarin is an anticoagulant normally used to prevent the formation of blood clots in the blood vessels and their migration elsewhere in the body

Question 20

How does warfarin slow blood clotting?

Answer 20

Warfarin decreases the body’s ability to form blood clots by blocking the formation of vitamin K-dependent clotting factors
Vitamin K is needed to make clotting factors and prevent bleeding