15 - Oxygen Transport Flashcards

1
Q

What is the structure of haemoglobin?

A
  • Quaternary structure
  • 4 subunits, 2a 2b, tetrameric
  • Each polypeptide chain has haem prosthetic group
  • Each chain similar to myoglobin
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2
Q

What is the structure of the haem group?

A

- Porphyrin planar ring with Fe in the middle

  • Free haem, Fe can make two bonds, one above and one below ring
  • Forms bond with histidine residue (proximal histidine) from protein, and one molecule of O2
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3
Q

What does it mean by prosthetic route in haem?

A

When Fe is bound to a histidine residue and one O2 rather than two O2’s

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4
Q

What is the structure of myoglobin?

A
  • Tertiary structure
  • 1 subunit
  • Mainly alpha helices (no beta)
  • Compact (globular)
  • Small
  • His 93 in 8th alpha helix is covalently linked to Fe
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5
Q

What happens to the shape of myoglobin when oxygen binds?

A
  • Fe is below the planar ring in deoxymyoglobin
  • When oxygen binds this causes movement of Fe into the plane of the ring, causing Histidine to move up so very small change in protein conformation when histidine moves
  • Not enough change to notice
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6
Q

What does the binding curve of myoglobin look like?

A
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7
Q

What does the haemoglobin binding curve look like?

A
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8
Q

What are the two states of haemoglobin?

A

T (tense) state: low affinity state, no o2 bound

R (relaxed) state: high affinity state, o2 bound

When O2 is bound it promotes stabilisation of the R state

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9
Q

What is the cooperative binding of oxygen?

A

As oxygen binds to haemoglobin, there is a conformational change in haemoglobin and this causes haemoglobin to have a higher affinity for O2

BINDING AFFINITY INCREASES AS MORE O2 BINDS

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10
Q

How does binding of oxygen to haemoglobin cause a change in conformation

A

Histidine pulling

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11
Q

Why is the cooperative effect important?

A

So oxygen binds at high partial pressure of oxygen and dissociates at low partial pressures of oxygen

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12
Q

What are the three ways oxygen binding is regulated?

A

1. 2,3-BPG (2,3 bisphosphate glycerate)

2. CO2 and H+

3. Carbon monoxide

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13
Q

What does 2-3 BPG do?

A
  • Allosterically binds to haemoglobin, stabilising the T form
  • Binds to positives on B-subunits
  • Decreases affinity for O2 and shifts curve to the right
  • In RBC at 5mM
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14
Q

How does 2,3-BPG concentration vary?

A
  • In highly metabolic tissues high BPG
  • At high altitudes more BPG produced
  • More BPG promotes oxygen release into tissues
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15
Q

What is the Bohr effect?

A
  • An increase in PCO2 OR a decrease in pH, causes a Hb to have a decrease in affinity for O2, curve shift to right
  • Allosteric binding
  • High metabolic tissues produce lots of H+ and CO2 so ensures oxygen release into tissue so supply can meet demand
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16
Q

How is carbon monoxide a poison?

A
  • Binds very tightly to Hb and irreversible
  • When bound to Hb it increases the affinity for O2 so other subunits can’t release their oxygen into tissue
  • Fatal when over 50% COHb
17
Q

What are the different types of haemoglobin and why are they different?

A

Different haemoglobins due to the different expressions of different polypeptide chains throughout life

18
Q

Where are the alpha and beta subunit genes located?

A

A (two genes) - chromosome 16

B (only 1 gene)- chromosome 11

19
Q

What haemoglobin is in fetuses?

A

HbF

a2γ2

Higher binding affinity for O2 than HbA so allows transfer of O2 from mother across the placenta

20
Q

How do you treat carbon monoxide poisoning?

A

Hyperbaric chamber or 100% O2 in rebreather mask

21
Q

What is sickle cell anaemia caused by?

A
  • Subsitution mutation in beta Hb (Glu –> Val)
  • Val hydrophobic not hydrophilic like Glu
  • Hb clump together to hide hydrophobic amino acid and become insoluble, stick to RBC membrane (sickling)
  • Prone to lysis as more rigid
22
Q

Outline the relationship between haemogloin curve, affinity and shape of haemoglobin?

A
  • Shift to right, decrease in affinity, T state
  • Shift to left, increase in affinity, R state
23
Q

What is Thalassaemia?

A

Genetic disease where there is an imbalance in alpha and beta chains so decrease in haemoglobin production

24
Q

What is b-thalassemia?

A
  • Decrease or absent b-globin chain
  • Onset at birth-age 2
  • a-chains can’t form stable tetramer
25
Q

What is a-thalassemia?

A
  • Decreased or absent a-globin chain
  • Different levels of severity due to two alpha genes
  • B chains can form stable tetramers but they have really high affinity for oxygen as no cooperativity
  • Intolerance to exercixse
  • Onset before birth
26
Q

What is HbH disorder?

A
  • It is a moderate-severe anaemia caused by alpha-thalassemia.
  • Autosomal recessive disorder
27
Q

Which haemoglobin has the highest affinity for 2,3BPG?

A

HbA, different side chains that BPG binds to