Session 10: Protein Function and Oxygen Transport Flashcards Preview

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Flashcards in Session 10: Protein Function and Oxygen Transport Deck (55):
1

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

Haemoglobin
Myoglobin

2

Apart from oxygen, Haemoglobin also transports what?

CO2 and protons

3

What is the role of myoglobin?

To act as a small oxygen reservoir in MUSCLE

4

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

Oxygen is not very water soluble

5

Describe the structure of haem

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

6

What is the function of the haem group?

To bind oxygen

7

Myoglobin is made up of how many polypeptide chains?

One

8

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

One oxygen molecule

9

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

One

10

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

Proximal histidine

11

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

alpha-helix

12

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

Histidine residue
In the 8th alpha-helix

13

Where does the Fe (Iron) sit in DEOXYmyoglobin?

Slightly below the plane of the ring

14

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

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

15

What shape is the oxygen binding curve for myoglobin?

Hyperbolic curve

16

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

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

17

What shape is the oxygen binding curve for haemoglobin?

Sigmoidal curve

18

Describe the structure of haemoglobin

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

19

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

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

20

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

R state "relaxed" - High affinity for oxygen
T state "tense" - Low affinity for oxygen

21

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

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

22

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

R state (high affinity)

23

Why is the binding curve for haemoglobin sigmoidal?

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

24

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

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.

25

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

Left

26

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

Right

27

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

2,3 Bisphosphoglycerate (BPG)

28

What affect does 2,3 BPG have on haemoglobin?

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

29

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

One

30

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

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

31

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

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

32

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

CO2 and Protons (H+)

33

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

They decrease haemoglobin's affinity for oxygen
The Bohr effect

34

Why is the Bohr effect important physiologically?

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

35

How does carbon monoxide poisoning lead to death?

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

36

What level of COHb is fatal?

>50%

37

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

Increases their affinity for oxygen

38

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

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

39

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

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

40

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

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

41

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

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

42

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

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

43

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

Haemoglobinopathies

44

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

Thalassemias

45

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

Autosomal recessive
Co-dominance

46

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

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

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

Glutamate
Negative
Valine
Neutral
Hydrophobic

48

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

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

49

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

Lyse

50

Name three pathological symptoms of sickle cell anaemia

Problems with the spleen
Recurrent infection
Ischemia due to tissue death

51

What are the two types of thalassemias?

Alpha and beta

52

In relation to genetic, thalassemias are ___________ __________

Autosomal recessive

53

Thalassemias result in an imbalance between _____ and _____ globins

Alpha
Beta

54

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

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

55

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

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