1.5 Haemoglobin & Gas exchange

Question 1

What is the only site of Haemoglobin

Answer 1

RBCs

Question 2

What is the main function of Hb

Answer 2

• transport of O2 from the lungs to the tissue capillaries

Question 3

What is the components of Hb

Answer 3

• Heme group (iron containing group)
• Globin (protein)

Question 4

What is the group of proteins that Hb belongs to

Answer 4

Hemeproteins

Question 5

What are Hemeproteins

Answer 5

Group of specialised proteins that contain heme as a tightly bound prostethic group

Question 6

Give 3 examples of hemeproteins

Answer 6

1. Myoglobin
2. Cytochrome
3. Catalase

Question 7

Why is Hb called a tetramer

Answer 7

because it has 4 polypeptides

Question 8

What type of interactions/bonds hold the 4 polypeptide chains together

Answer 8

non-covalent bonds

Question 9

What are the 2 dimers in the tetramer of Hb

Answer 9

alpha1beta1
alpha2beta2

Question 10

What are the bonds inside the dimers (intrachain) that forms strong associations between alpha and beta subunits

Answer 10

• Hydrophobic interactions

Question 11

What type of interactions exist between the dimers and what is the role of them

Answer 11

Type:
- Ionic
- Hydrogen bonds

Role:
Allows for the movement of the dimers (flexibility)

Question 12

What is the significance of the weaker (polar) interactions

Answer 12

Results in the 2 dimers occupying different energy levels in Deoxyhaemoglobin & oxyhaemglobin

Question 13

Compare & contrast the T (taut form) and R (relaxed) form of haemgoglobin in terms of:
- binding of oxygen
- flexibility
- affinity to O2

Answer 13

T form:
- binding of oxygen: Deoxy form
- flexibility: H-bonds and ionic bonds constraint the movement of the dimers
- affinity to O2: low

R form:
- binding of oxygen: oxygen bound (oxy) form
- flexibility: H-bonds and ionic bonds rupture due to the oxygen binding, resulting in more freedom of movement the dimers
- affinity to O2: high
(corporative binding of O2)

Question 14

What is the heme complex made of?

Answer 14

a complex of:
- protoporphyrin IX
- ferrous iron (Fe2+)

Question 15

What are the 6 bonds that the Fe2+ can

Answer 15

• 4 bonds with nitriogen (N):
  the iron is held in the centre of the heme molecule by bonds to the four nitrogen of the porphyrin ring
• 1 bond (below the ring) with the histidine side chain of globin protien:
• 1 bond (above the ring): available to bind O2

Question 16

What causes the formation of Methaemoglobin MetHb

Answer 16

• Oxidation of Hb to the ferric (Fe3+) state forms methaemoglobin
• The oxidation may be caused by the action of certain drugs or H2O2

Question 17

What enzyme corrects the occasional oxidation of Fe2+ to Fe3+

Answer 17

enzyme NADH-cytochrome b5 reductase

Question 18

What is the difference between Haemoglobin & Methaemoglobin

Answer 18

Methaemoglobin :
- cannot bind to oxygen
- instead they contain water at the sixth coordinate position of Fe3+

Question 19

What is the 3 main functions of Haemoglobin (Hb)

Answer 19

1. transport of molecular O2:
   from the lungs to the tissues
2. transport of CO2:
   from the tissues to the lungs
3. buffering of the blood: (reversible proton exchange)
   to prevent changes in pH

Question 20

What are the 2 ways Oxygen is transported in the blood

Answer 20

1. bound to Hb
2. dissolved in plasma
   - Oxygen is poorly soluble in water only about 1.5% is carried in the dissolved form in plasma

Question 21

Describe the transport of O2 bound to Hb

Answer 21

• Each Hb molecule can combine with four molecules of O2 (as there are 4 Fe2+ containing heme groups)
• the process of O2 binding is very rapid and reversible

Question 22

What are the 2 forms of haemoglobin and where are they formed

Answer 22

1. oxyhaemoglobin (HbO2):
   The haemoglobin-oxygen combination (formed in lungs)
2. deoxyhaemoglobin (HHb) / reduced Hb
   Hb that has released O2 (formed in the tissues)

Question 23

What is the equation involving O2 transport in lungs and tissues

Answer 23

HHb + O2 < –> HbO2 + H+

• forward: in lungs (oxygen bound, oxyhemoglobin)
• backward: in tissues (oxygen released, deoxyhemoglobin)

Question 24

What is heme-heme interaction

Answer 24

• The binding of an O2 molecule to one heme group increases the O2 affinity of the remaining heme groups in the same Hb molecule

Question 24

What is the reason behind heme-heme interaction

Answer 24

After binding to the first O2, the Hb molecule undergoes a change in its 3-D shape and this increases its affinity for O2 : T form --> R form

Question 25

What is the relative difference between affinity for the first O2 and the last O2

Answer 25

the last O2 has x300 greater affinity than the first

Question 26

When unloading which O2 has the highest affinity

Answer 26

- the first O2 and the affinity decreases as the unloading happens - easily released

Question 27

What is thee difference between fully saturated Hb and partially saturated Hb

Answer 27

- When all four of its heme groups are bound to O2, a Hb molecule is said to be fully saturated; - when one, two or three O2 molecules are bound, Hb is partially saturated

Question 28

What is the main determinant of Hb affinity to oxygen

Answer 28

Partial Pressure (PO2)

Question 29

What is meant by the partial pressure of Oxygen

Answer 29

the amount of O2 dissolved in plasma, not the amount bound to Hb

Question 30

Describe the O2-Hb dissociation curve

Answer 30

Plot of Hb saturation against PO2

Question 31

Explain the shape of the O2-Hb dissociation curve

Answer 31

- Shape of the plot : sigmoid (“S”) - indicates cooperative binding of O2 (heme-heme interaction) by Hb

Question 32

Explain the left and right shift of O2-Hb dissociation curve

Answer 32

When the curve shifts to the left: - Affinity of Hb for O2 increases - Hb does not readily release O2 to tissues When the curve shifts to the right: - affinity of Hb for O2 decreases - increased delivery of O2 to the tissues

Question 32

Describe the O2-Hb dissociation curve at different PO2

Answer 32

PO2 < 10 mm Hg - Hb has a very low affinity for O2 PO2 = 10 - 50 mm Hg - the curve is steep, - O2 affinity increases substantially. - generally found in the tissues PO2 = 70 - 100 mm Hg - the curve begins to flatten rapidly towards the area of 100% saturation. - found in the alveoli of the lungs

Question 33

What are the 4 factors that affect the Hbs affinity for O2

Answer 33

1. Blood (body) temperature 2. Blood pH 3. CO2 4. 2,3- Biphophoglycerate (2,3-BPG)

Question 34

What is the effect on the affinity of Hb for oxygen when: temperature increases

Answer 34

- Hb-O2 dissociation curve shifts to the right - affinity of Hb for O2 increases - physiological advantage : - active tissues are typically warmer - more O2 is released from Hb in the vicinity of hard-working tissues

Question 35

What is the effect on the affinity of Hb for oxygen when: pH decreases ( [H+] increases)

Answer 35

- weakens the strength of the Hb-O2 bond - the affinity of Hb for O2 decreases - O2 unloading to the tissues increases - this phenomenon is called Bohr effect

Question 36

What is the effect on the affinity of Hb for oxygen when: CO2 increases

Answer 36

- blood pH decreases, - Hb affinity for O2 decreases - O2 unloading increases - beneficial because active tissues release more CO2 and generate more H+, both of which accelerate the release of O2 from oxyhaemoglobin to such tissues

Question 37

What does 2,3-BPG stand for

Answer 37

2,3-biphosphoglycerate: - RBC lack mitochondria: glucose metabolism is entirely anaerobic (i.e. through glycolysis) - 2,3-BPG is synthesised from an intermediate of the glycolytic pathway

Question 38

What is the effect on the affinity of Hb for oxygen when: 2,3-BPG increases

Answer 38

- shifts the Hb-O2 curve to the right - O2 affinity of Hb decreases - O2 unloading increases

Question 39

In which conditions does 2,3-BPG increases:

Answer 39

- chronic hypoxia - obstructive pulmonary emphysema - high altitudes - chronic anaemia

Question 40

What is the Fetal Hb made up of:

Answer 40

consists of 2 alpha and 2 gamma chains

Question 41

What is the difference between adult and feral Hbs affinity for O2

Answer 41

under physiologic conditions, - Hb F has a higher affinity for O2 than does HbA - because it only binds weakly to 2,3-BPG (2,3-BPG usually lowers the affinity but since it binds weakly, the O2 loading is stronger)

Question 42

What is the shape of the O2 dissociation curve for Myoglobin & what does it reflect

Answer 42

hyperbolic shape This reflects the fact that Mb reversibly binds a single molecule of O2 Mb + O2 <--> MbO2

Question 42

What is the importance of myoglobin in muscle cells

Answer 42

- Mb binds O2 released by Hb at the low PO2 found in the muscle - Mb releases O2 within the muscle cell in response to O2 demand when PO2 is very low

Question 43

What are the 3 forms of CO2 transportation

Answer 43

1. as a gas dissolved in plasma - 7% to 10% 2. chemically bound to Hb - 20% - 30% - carried within the RBC as carbaminohaemoglobin CO2 + Hb <--> HbCO2 - CO2 binds directly to the amino acids of the globin 3. in plasma as bicarbonate ion (HCO3-) - the largest fraction of CO2 (60 - 70%) is converted to HCO3- and transported in plasma - CO2 diffuses into the RBC, combining with water to form unstable carbonic acid (H2CO3), which quickly dissociates into H+ and HCO3- CO2 + H2O <---> H2CO3 <---> H+ + HCO3- carbonic anhydrase enzyme does this conversion

Question 44

What counterbalances the rapid outrun of HCO3- from the RBC into plasma

Answer 44

Cl- shift from plasma into the blood

Question 45

Compare the Hbs affinity for both O2 and CO

Answer 45

- The affinity of Hb for CO is x 200 greater than that for O2 - Even at very low partial pressures, CO can displace O2

Question 46

What forms when CO binds to Hb

Answer 46

carbon monoxyhaemoglobin

Question 47

What are the symptoms that CO poisoning results in:

Answer 47

- the victim becomes confused and has a throbbing headache - hyperbaric therapy is given to clear from the body