MGD S2 - Haemoglobin, Myoglobin and Enzymes

Question 1

Describe structure and function of myoglobin

Answer 1

Single subunit
One haem group
Hyperbolic binding
No cooperativity

Question 2

Describe structure and function of hemoglobin

Answer 2

Tetrameric
Four haem groups
Sigmoidal binding
Cooperative binding (hence Sigmoidal)

Question 3

What are the two states of haemoglobin and their relative oxygen affinities?

Answer 3

Low affinity t state

High affinity r state

Question 4

What prompts 2,3-BPG release in the body?

Answer 4

High altitudes

Released in metabolism

Question 5

What effect does CO inhalation have on the body?

Answer 5

Binds to Hb 250x more readily than O2 and at >50% Hb bound to CO this effect is fatal.
CO binding to Hb increases other subunits affinity for oxygen.

Question 6

What effect do the genetic defects of sickle cell anaemia have on a patients physiology?

Hint: What is the effect on Haemoglobin and what are the knock on effects?

Answer 6

Substitution for valine creates a sticky hydrophobic pocket that allows deoxygenated Hb to polymerise.
This leads to the distortion of RBCs leading to the sickle shape.
Sickle shape causes blockages in microvasculature.

Question 7

What is the symptomatic difference between alpha and beta thalassaemia?

Answer 7

Alpha thalassaemia symptoms appear before birth

Beta thalassaemia symptoms appear after birth

Question 8

Describe alpha thalassaemia

Answer 8

Decreased or absent alpha chains

Multiple levels of severity due to multiple copies of alpha chain genes (some correct alpha chains produced by correct copies)

Rarer than beta

Can form unstable Hb tetramers (tetrameric beta) with increased O2 affinity

Symptoms appear before birth

Question 9

Describe beta thalassaemia

Answer 9

Decreased or absent beta chains

Cannot form stable tetramers

Symptoms appear after birth

Question 10

Define Km

Answer 10

Michaelis Menten constant

This is the substrate conc that gives 1/2 Vmax

Question 11

What effect do competitive inhibitors have on enzyme kinetics?

Answer 11

Will not prevent Vmax being reached

Adding more substrate will overcome the effect of the inhibition

Question 12

What is the significance of myoglobin’s very high oxygen affinity?

Answer 12

Will only release O2 when pO2 very low

Question 13

Why does Hb have a Sigmoidal O2 affinity curve

Answer 13

As the Hb binds to oxygen it increases in affinity (transitions from t to r state)

Question 14

What effect does 2,3-BPG have on the body?

Answer 14

Decreases haemoglobin oxygen affinity prompting oxygen release in all tissues

Question 15

What effect does metabolic rate have on 2,3-BPG release and why is this beneficial?

Answer 15

Higher metabolic rate prompts more BPG release and hence haemoglobin releases oxygen in proportion with level of metabolism.

Question 16

Explain fully the Bohr effect.

Answer 16

Increased concentration of CO2 and H+ in tissues (eg exercising muscle) prompts Hb to lower its oxygen affinity and hence release more oxygen to the tissue.

Question 17

What type of disorder is sickle cell anemia?

Answer 17

Autosomal recessive blood disorder

Question 18

What is the direct genetic cause of sickle cell anaemia and where does it occur?

Answer 18

Substitution of glutamate for valine on the B-globulin subunit of haemoglobin.

Question 19

What is thalassaemia?

Answer 19

A group of genetic disorders that leads to imbalance between Alpha and Beta Hb subunits.

Question 20

What is the function of enzymes and how do they perform this function?

Answer 20

They catalyse reactions (increasing rate) by binding the substrate the active site of the enzyme increasing local concentration of the substrate and stabilising the formation of the high energy transition state.

Question 21

How do enzyme and substrate concentration affect rate of reaction?

Answer 21

Increase in conc of enzyme or substrate leads to hyperbolic increase of rate of reaction up to Vmax (saturation).

Question 22

Define Vo

Answer 22

Rate of reaction

Question 23

What is the michaelis menten equation?

Answer 23

Describes how Vo varies with substrate conc.

Vo = (Vmax x [S]) / (Km + [S])

Question 24

What effect does non-competitive inhibition have on enzyme kinetics?

Answer 24

Prevents Vmax from being reached, has no effect on Km

Question 25

Describe the changes of globin chains throughout development from -9 months to 6 months

Answer 25

Alpha-like globins:
- Initially xi then to alpha at - 7 months

Beta-like chains:

• Initially epsilon, then to gamma at - 7 months
• Then gamma to beta at 1-2 months after birth