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Flashcards in Haemoglobin & Myoglobin Deck (41)
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1

Why must oxygen bind a transporter to be transported around the body?

It is not very soluble in water

2

Describe the features of myoglobin structure.

It is a single polypeptide made 153 amino acids and is mainly (75%) alpha-helical - histamine 93 in the 8th alpha helix is covalently linked to the iron

3

Describe the structure of haem. Which part binds oxygen?

Haem is composed of a protoporphyrin ring and an iron ion attached to 4 nitrogen molecules - the iron ion (Fe2+) is what attaches to the oxygen molecule

4

How many molecules bind the haem group in haemoglobin and myoglobin?

1 molecule of oxygen

5

How is the iron ion bound to the protoporphyrin ring in a haem molecule?

The iron ion is attached to the protoporphyrin ring via a histidine residue

6

How does oxygen binding cause a change in the configuration of a myoglobin molecule?

In its deoxygenated form, the iron ion sits slightly below the plane of the protoporphyrin ring of myoglobin - when oxygen binds, it causes a conformational change causing the iron ion to punch upwards into the same plane of the protoporphyrin ring

7

What is the P50?

The partial pressure at which 50% of haemoglobin/myoglobin is saturated with oxygen

8

Describe some features of the structure of haemoglobin.

An assembly of 4 globular protein subunits - 2 alpha subunits and 2 beta subunits - each subunit contains a haem group which can bind a single oxygen molecule - haemoglobin can therefore bind 4 oxygen molecules

9

In what 2 states can deoxyhaemoglobin exist? Which state does oxygen binding promote?

In a low affinity T state or a high affinity R state - oxygen binding promotes stabilisation of the R state

10

How does oxygen-binding affect the conformation of haemoglobin?

Oxygen-binding instigates a conformational change that rotates all subunits by around 15 degrees - the haem groups become much more exposed, so oxygen can bind easier - this changes the haemoglobin from the T state to the R state - like myoglobin, the conformational change pushes the iron group into the same plane as they protoporphyrin ring

11

On an oxygen dissociation curve, what does a shift in the curve to the right mean?

Myoglobin/haemoglobin has a lower affinity for oxygen binding

12

On an oxygen dissociation curve, what does a shift in the curve to the left mean?

Myoglobin/haemoglobin has a greater affinity for oxygen binding

13

Why is the oxygen binding curve for haemoglobin sigmoidal?

Due to the allosteric changes that oxygen binding induces (rotating the haem groups by 15 degrees) - the binding affinity for oxygen increases as each oxygen molecule binds - the binding of the 1st oxygen molecule is hard, while the binding of the 4th oxygen is relatively easier - this then produces the sigmoidal curve seen on the oxygen binding curve

14

What does 'co-operative' binding of oxygen to haemoglobin describe?

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

15

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

BPG changes the affinity of haemoglobin for oxygen, making it a more efficient transporter of oxygen - it actually decreases the affinity of haemoglobin for oxygen

16

What are general levels of BPG present in red blood cells?

Around 5nm

17

How many molecules of BPG bind per haemoglobin tetramer?

1 molecule of BPG binds per haemoglobin tetramer

18

How are BPG concentrations affected at high altitudes?

BPG concentrations are greater at higher altitudes, which promotes oxygen dissociation from haemoglobin at tissues

19

How does BPG affect the position of an oxygen dissociation curve?

It will shift the curve to the right

20

How does binding of hydrogen and carbon dioxide affect the affinity of haemoglobin for oxygen?

Their binding decreases haemoglobins affinity for oxygen

21

How does carbon dioxide (CO2) bind haemoglobin?

Carbon dioxide covalently attaches to the N-terminus of haemoglobin

22

What is the Bohr Effect? What does this ensure?

The Bohr Effect suggests that the H+ and CO2 produced by metabolically active cells produce acidic conditions (via lactate and carbonic acid) that encourage the dissociation of oxygen (and association of CO2) to haemoglobin - this ensures the delivery of O2 is proportional to its demand

23

How does a pH increase affect an oxygen dissociation curve?

It will shift the curve to the right, which decreases the affinity its of haemoglobin for oxygen

24

Why is carbon monoxide a poison?

It combines with ferromyoglobin and ferrohaemoglobin and blocks oxygen transport, leading to cell death

25

How much more readily will haemoglobin bind with carbon monoxide than oxygen?

Carbon monoxide binds haemoglobin 250X more readily than oxygen does

26

When does carbon monoxide binding become fatal?

When 50% of haemoglobin are bound to carbon monoxide

27

What mutation leads to sickle cell anaemia? Why is this mutation so detrimental?

A mutation of glutamate to valine in a beta globin - valine is highly hydrophobic and so buries itself within the globin - 2 'sickle cells' may bind to try and mask their hydrophobic regions, giving the sickle cells their 'sticky' characteristics - furthermore, this is exacerbated in their low-affinity deoxygenated state, and so cluster is a deoxygenated state

28

What are 2 pathologies of sickle cells?

Sickle cells are more likely to lyse, leading to anaemia - they are also more rigid, and tend to block vasculature

29

What are thalassaemias? Are they heterozygous or homozygous?

Thalassaemias are a group of genetic disorders where there is an imbalance between the number of alpha- and beta- globin chains - heterozygotes are only minor lay affected - homozygous are greatly affected

30

Describe the pathology of B-thalassaemias.

B-thalassaemias describe a decreased or absent production of beta globins - alpha globins are unable to form stable tetramers