Biological Gas Transport

Question 1

What are the three necessary components?

Answer 1

• A surface for gas exchange
• A system for efficiently moving solutions
• An efficient oxygen transport protein

Question 2

Over approximately what distance does gas exchange occur over in alveoli?

Answer 2

0.3 micrometres

Question 3

The concentration of Hb in an erythrocyte is…

Answer 3

5mM

Question 4

What is the lifetime of an erythrocyte?

Answer 4

120 days

Question 5

Why is packaging of Hb in erythrocytes essential?

Answer 5

To decrease viscosity to keep viscosity at a physiologically reasonable level

Question 6

Per 100mL, what is the amount of oxygen with and without Hb?

Answer 6

Without - 0.3mL

With - 20mL

Question 7

The alpha chain is encoded on which chromosome?

Answer 7

16

Question 8

The beta chain is encoded on which chromosome?

Answer 8

11

Question 9

Why is three different forms of Hb required in humans?

Answer 9

So the body can respond to the different oxygen sources at different phases of development and the different property demands

Question 10

Erythrocytes originate from what?

Answer 10

Reticulocytes, which in turn come from Stem Cells

Question 11

State the number of amino acids in the alpha chain

Answer 11

141

Question 12

State the number of amino acids in the beta chain

Answer 12

146

Question 13

Embryonic Hb is synthesised in…

Answer 13

The Yolk Sac

Question 14

Fetal Hb is synthesised in…

Answer 14

The Liver

Question 15

Adult Hb is synthesised in the…

Answer 15

Flat bones

Question 16

At birth our Hb is…

Answer 16

Roughly 50% of both HbF and HbA

Question 17

Why is steric intereference in the Hb molecule important?

Answer 17

To prevent Fe2+ from oxidising into the more stable Fe3+, as this would bind the oxygen too tightly for efficient oxygen transport.

Question 18

Steric intereference in our Hb is created by…

Answer 18

The distal histidine, which prevents vertical binding of oxygen

Question 19

How is Hb assembled?

Answer 19

Spontaneously at quick rates

Question 20

What is the Hill coefficient?

Answer 20

• An expression of the level of co-operativity

- The gradient of the oxygen binding curve around p50

Question 21

What is p50?

Answer 21

The concentration of oxygen when 50% of binding sites are occupied
This is typically 26-28mmHg for Hb

Question 22

What are the 3 models which have been used to explain the homotropic effect?

Answer 22

• The two state concerted model
• The sequential model
• The stereochemical model (qualitative)

Question 23

Describe the two state concerted model

Answer 23

• Quantitative with near perfect experimental fit
• Theorises that there are two quaternary structures of Hb with different binding affinity - T (low) and R (high)
• Both forms are present in equilibrium, with altering quantities of each form

Question 24

Describe the sequential model

Answer 24

• Quantitative with near perfect experimental fit
• Theorises that during oxygenation the quaternary structure will go through a series of subunit changes, with each changing slightly as oxygen is bound. These forms range from T (tense) state, when no oxygen is bound, to R (relaxed) when all subunits have oxygen bound

Question 25

Describe the stereochemical/Perutz model

Answer 25

- Qualitative - Based on X-ray structure of oxy and deoxy structures - Says that the binding of oxygen to haem group makes the gap where a tyrosine is sitting smaller, forcing it out, and hence breaking ionic bonds between the neighbouring subunits, increasing the affinity of the neighbouring subunit to oxygen - Does not specify if all subunits are activated simultaneously or sequentially

Question 26

Name some heterotropic allosteric inhibitors of Hb

Answer 26

Cl-, H+, 2,3DPG

Question 27

What is the Bohr effect?

Answer 27

The lowering of pH reduces the oxygen affinity of Hb through the allosteric inhibition of Hb by H+ The impact of pH is linear over the human physiological pH range.

Question 28

When is 2,3DPG bound to Hb?

Answer 28

Under normal conditions there are equal amounts of Hb and DPG produced and Hb is usually bound by DPG

Question 29

How does DPG lower the oxygen affinity of Hb?

Answer 29

By stabilising the beta subunits in the deoxygenated form

Question 30

How is 2,3DPG synthesised?

Answer 30

It is formed only in red blood cells, and is a side product of Glycolysis It is formed from 1,3DPG by a mutase, and can re-enter the glycolytic pathway by being converted by phosphatase into 3PG.

Question 31

What is the difference between the gamma and beta chains of Hb?

Answer 31

One of the Histidines of the beta subunit structure is changes to a Serine (OH group not ionizable at normal pH). This results in the binding site of DPG being less charged, so it binds less tightly.

Question 32

What is the effect of temperature to Hb in humans?

Answer 32

An increase in termperature lowers the oxygen affinity of Hb This is useful for an increased oxygen delivery during exercise