Session 10: Protein Function and Oxygen Transport

Question 1

What two molecules are responsible for the transport of oxygen in the body?

Answer 1

Haemoglobin

Myoglobin

Question 2

Apart from oxygen, Haemoglobin also transports what?

Answer 2

CO2 and protons

Question 3

What is the role of myoglobin?

Answer 3

To act as a small oxygen reservoir in MUSCLE

Question 4

Why is it necessary that oxygen is carried by transporters in the body?

Answer 4

Oxygen is not very water soluble

Question 5

Describe the structure of haem

Answer 5

Haem consists of:
A protoporphyrin ring
A Fe atom
Four Nitrogen atoms

Question 6

What is the function of the haem group?

Answer 6

To bind oxygen

Question 7

Myoglobin is made up of how many polypeptide chains?

Answer 7

One

Question 8

How many molecules of oxygen can bind to the haem group(s) of haemoglobin and myoglobin?

Answer 8

One oxygen molecule

Question 9

How may haem groups are there per polypeptide chain in haemoglobin and myoglobin?

Answer 9

One

Question 10

How does the Fe (Iron) atom bind to the haem protein and hold it in the ring?

Answer 10

Proximal histidine

Question 11

Myoglobin is made up by 75% of what secondary protein structure?

Answer 11

alpha-helix

Question 12

The alpha-helix is myoglobin is covalently linked to what? Where does it make this link?

Answer 12

Histidine residue

In the 8th alpha-helix

Question 13

Where does the Fe (Iron) sit in DEOXYmyoglobin?

Answer 13

Slightly below the plane of the ring

Question 14

In deoxymyoglobin, what happens to the Fe when oxygen binds?

Answer 14

It moves up into the plane of the ring which causes movement of the histidine residue and a change in the overall conformation of myoglobin

Question 15

What shape is the oxygen binding curve for myoglobin?

Answer 15

Hyperbolic curve

Question 16

What is p50 and what is its constant value in myoglobin?

Answer 16

The partial pressure of oxygen at which the saturation of oxygen binding to myoglobin is 50%
2 torr

Question 17

What shape is the oxygen binding curve for haemoglobin?

Answer 17

Sigmoidal curve

Question 18

Describe the structure of haemoglobin

Answer 18

4 polypeptide chains

A haem group attached to each polypeptide chain, each with the capability of binding an oxygen

Question 19

What is important for defining the sigmoidal shape of haemoglobin’s oxygen binding curve?

Answer 19

The entire molecular structure and how it can change to give high and low affinity states

Question 20

Haemoglobin exists in two states relative to its binding affinity. What are they?

Answer 20

R state “relaxed” - High affinity for oxygen

T state “tense” - Low affinity for oxygen

Question 21

Describe the differences in the structure between the R and T state and how this relates to haemoglobin’s affinity for oxygen

Answer 21

T state: The haem groups are not exposed and the structure is stabilised by interactions between histidine (+) and aspartate (-) residues–> LOW AFFINITY
R state: Is rotated around 15 degrees which means the interactions can no longer be made and the haem groups are exposed for oxygen to bind to –>HIGH AFFINITY

Question 22

The binding of oxygen promotes the formation of which of the two states of haemoglobin?

Answer 22

R state (high affinity)

Question 23

Why is the binding curve for haemoglobin sigmoidal?

Answer 23

Cooperative binding of oxygen

The binding affinity for oxygen increases as more oxygen molecules bind to the subunits

Question 24

Explain how the “cooperative binding” of oxygen in haemoglobin is relevant to its function in the body

Answer 24

In areas of low partial pressure of oxygen, the affinity for binding oxygen is low and therefore the haemoglobin is likely to release oxygen to the tissues where it is neded.
When partial pressures of oxygen are high, the affinity for binding oxygen is high and therefore the haemoglobin is more inclined to pick up all available oxygen and become fully saturated, in the lungs.

Question 25

A shift of the oxygen binding curve to the ______ indicates a higher affinity for oxygen

Answer 25

Left

Question 26

A shift in the oxygen binding curve to the _____ indicates a lower affinity for oxygen

Answer 26

Right

Question 27

What molecule is responsible for the regulation of oxygen binding to haemoglobin?

Answer 27

2,3 Bisphosphoglycerate (BPG)

Question 28

What affect does 2,3 BPG have on haemoglobin?

Answer 28

2,3 BPG lowers haemoglobin's affinity for oxygen to make it more efficient for transporting around the body

Question 29

How many molecules of 2,3 BPG bind per tetramer of haemoglobin?

Answer 29

One

Question 30

Where and how does 2,3 BPG interact with haemoglobin?

Answer 30

In the middle | Via electrostatic interactions between positively charged histidine and lysine residues

Question 31

Under what conditions does 2,3 BPG increase? Why?

Answer 31

At high altitude | Promotes oxygen release as it lowers haemoglobin's affinity for oxygen

Question 32

Apart from BPG, what other molecules are responsible for the regulation of oxygen binding?

Answer 32

CO2 and Protons (H+)

Question 33

What affect do CO2 and H+ have on haemoglobin's affinity for oxygen? This is known as what?

Answer 33

They decrease haemoglobin's affinity for oxygen | The Bohr effect

Question 34

Why is the Bohr effect important physiologically?

Answer 34

Metabolically active tissues produce large amounts of CO2 and lactate (H+) which lowers the pH in these tissues tissues. At lower pH, O2 affinity is reduced and therefore O2 is released in those tissues where it is needed

Question 35

How does carbon monoxide poisoning lead to death?

Answer 35

CO combines with ferromyoglobin and ferrohaemoglobin 250 X more readily than O2 does, which means it bind tightly and irreversibly, blocking oxygen transport

Question 36

What level of COHb is fatal?

Answer 36

>50%

Question 37

What does carbon monoxide binding to haemoglobin do to the other subunits?

Answer 37

Increases their affinity for oxygen

Question 38

What could possibly reverse the binding of carbon monoxide to haemoglobin?

Answer 38

By increasing the partial pressure of oxygen (pO2), in a hyperbaric chamber

Question 39

The three normal adult haemoglobins are what? | In what percentages are they found in the blood?

Answer 39

``` Haemoglobin A (90%) Haemoglobin A2 (2-5%) Haemoglobin F (<2%) ```

Question 40

How does foetal haemoglobin differ from adult (maternal) haemoglobin?

Answer 40

Foetal haemoglobin has a higher affinity for oxygen than adult (maternal) haemoglobin so that it can transfer oxygen to the foetal blood supply from the mothers

Question 41

Allosteric inhibitors do what to the oxygen binding curve of haemoglobin?

Answer 41

Decreases the binding affinity of haemoglobin for oxygen which shifts the curve to the right

Question 42

Allosteric activators do what to the oxygen binding curve of haemoglobin?

Answer 42

Increases the binding affinity of haemoglobin for oxygen, which shifts the curve to the left

Question 43

Diseases that relate to the incorrect SHAPE of haemoglobin are called what?

Answer 43

Haemoglobinopathies

Question 44

Diseases that relate to the incorrect PRODUCTION of haemoglobin are called what?

Answer 44

Thalassemias

Question 45

With regard to inheritance sickle cell disease is an ___________ __________ disease that shows ______________

Answer 45

Autosomal recessive | Co-dominance

Question 46

What do we mean by when we say the sickle cell gene shows co-dominance?

Answer 46

The disease is recessive, but carriers of the gene for sickle cell haemoglobin will show sickle cell trait which means they have some normal RBCs and some sickle cell RBCs

Question 47

In sickle cell anaemia, the ___________ residue with a _________ charge is mutated to a __________ with a ___________ charge. This means that the valine is ___________ in relation to it's relationship with water

Answer 47

``` Glutamate Negative Valine Neutral Hydrophobic ```

Question 48

What does the affect of the single base pair mutation changing the glutamate to a valine have on haemoglobin?

Answer 48

The valine residues want to be hidden from the surface of the molecule and will therefore cluster to form a long molecule which interacts with the membrane and forms a sickle shaped cell

Question 49

Sickle cells are more prone to _______ and clog narrow blood vessels

Answer 49

Lyse

Question 50

Name three pathological symptoms of sickle cell anaemia

Answer 50

Problems with the spleen Recurrent infection Ischemia due to tissue death

Question 51

What are the two types of thalassemias?

Answer 51

Alpha and beta

Question 52

In relation to genetic, thalassemias are ___________ __________

Answer 52

Autosomal recessive

Question 53

Thalassemias result in an imbalance between _____ and _____ globins

Answer 53

Alpha | Beta

Question 54

What is seen in relation to alpha and beta chains in alpha thalassemia?

Answer 54

beta chains form stable tetramers with INCREASED affinity for oxygen, this oxygen will therefore not be released to tissues

Question 55

What, in relation to beta and alpha globins, is seen in beta thalassemia?

Answer 55

Excess alpha chains cause problems as they precipitate and form lumps of protein