CGIER 36 - Haemoproteins II: Co-operative oxygen binding to haemoglobin binding of CO2 and H+

Question 1

oxygenation reaction

Answer 1

Hb + 4O2< —->Hb(O2)4

Question 2

where does oxygenation occur and why

Answer 2

in lungs where there is a high concentration of haemoglobin

Question 3

what are the conditions muscles are in

Answer 3

low O2 and pH from respiration

Question 4

why would haemoglobin not have O2

Answer 4

when pH and O2 is low affinity of myoglobin for oxygen is greater than that of haemoglobin (see previous slide) and O2 is transferred from oxyhaemoglobin to myoglobin

Question 5

respiration equation

Answer 5

C6H12O6 + 6O2 —>6 CO2 + 6 H2O

Question 6

why is pH and O2 low in muscle

Answer 6

respiration occurs in muscles O2 is used to release CO2 which will make weak carbonic acid and water
H+ is also produced by metabolism in the muscle cells.

Question 7

how is CO2 and H+ transported to the lungs

Answer 7

free haemoglobin in muscles bind to CO2 and H+ and transports it to the lungs

Question 8

how does CO2 react in blood when CO2 is transported

Answer 8

Most CO2 produced in respiration reacts with water (catalysed by carbonic anhydrase) and is converted to bicarbonate (HCO3-) in erythrocytes

Question 9

other ways in which CO2 react with blood in carbon dioxide transport

Answer 9

Some however reacts with haemoglobin and forms a carbamate (a carboxylic acid with an amino group directly
attached) - CO2 binds to N atom from amino group of haemoglobin

Question 10

cooperative oxygen binding

Answer 10

Addition of the 1st O2 molecule to haemoglobin is difficultHowever when this happens the Fe(II) to which it binds changes from high-spin to low-spin
The Fe(II) shrinks & moves out of  porphyrin plane into it.
proximal histidine along with globin chain moves salt linkages break haem groups are exposed and more relaxed strcuture allowing 3 more Oxygens in

Question 11

describe structure particularly compactness of haemoglobin

Answer 11

Haemoglobin is a compact (tense) structure in which the globin chains interact by salt (electrostatic)
linkages.

Question 12

allosteric proteins

Answer 12

An allosteric protein is one in which an interaction at one site in the molecule affects interactions at remote sites. e.g. haemoglobin NOT myoglobin

Question 13

allosteric effects in haemoglobin

Answer 13

O2 binding at one site of haemoglobin helps binding of other O2 in remote sites of same molecule
Binding of H+ and CO2 at particular lead to charged groups being formed leads to formation of salt linkage - tense state - O2 removed
capillaries of alveoli of lungs binding of O2 in Hb causes breaking of salt bridges and release of CO2 and H+

Question 14

Bohr Effect

Answer 14

The inter-relationship between H+, CO2 and O2

binding in haemoglobin

Question 15

how is carbon monoxide made

Answer 15

when carbon is burned in insufficient Oxygen

Question 16

describe gaas carbon monoxide

Answer 16

odourless colourless gas

Question 17

where is carbon monoxide

Answer 17

exhaust fumes of cars mainly ones w/o catalytic converters, house fires, poorly maintained oil or gas heaters.

Question 18

why is carbon monoxide toxic?

Answer 18

The affinity of haemoglobin for CO is 225 times greater than its affinity for O2
Affinity of myoglobin for CO is ~ 25 times greater than its affinity for O2
Binding to CO instead of O2 - respiration cannot occur and one can die
The binding is so strong it is regarded as irreversible

Question 19

how could CO be more toxic

Answer 19

If the Fe-C≡O group was linear (thus more stable) and no H-bonding was involved the affinity of haemoglobin for C≡O would be 25,000 times greater than affinity for O2.
CO is more stable with histidine than with O2

Question 20

how was the body engineered itself to make CO less toxic

Answer 20

Nature engineered a way to reduce stability of CO complex and increase stability of O2 complex.

Question 21

explain the importance of distal histidine

Answer 21

The distal histidine which is located close to the O2 and CO binding site on the haem forces CO to bind at an angle
This destabilises the Hb(CO)4 complex.

Question 22

distal histidine’s involvement in destabilising the Hb(CO)4 complex is an example of..

Answer 22

allosteric effect

Question 23

how is oxygen stabilised in haem group

Answer 23

of strong H bonding between a partial negative charge on the non-bridging oxygen and the distal histidine.

Question 24

which complex is distal histidine more responsible for stabilising oxyhaemoglobin or carbonmonoxyhaemoglobin

Answer 24

The distal histidine stabilises oxyhaemoglobin by hydrogen bonding – more than it does carbonmonoxyhaemoglobin

Question 25

how is carbon monoxide poisoning treatment

Answer 25

CO poisoning is treated by administering pure O2 under high pressure (2 or 3 atm) in hyperbaric units

Question 26

why is carbon monoxide poisoning treated by administerd pure O2 under high pressure

Answer 26

Under these conditions O2 dissolves in the plasma to a much higher degree than usual and tissues receive enough oxygen to recover.

Question 27

how much exposure to O2 is dangerous and how does it affect the body

Answer 27

exposure to O2 at 2 atm for 6 hours causes damage to lung tissues and the central nervous system.

Question 28

what is the recommended time and pressure of administering O2 to body

Answer 28

2 hrs at 2 atm or 1½ hrs at 3 atm