Agents that affect oxygen binding

Question 1

What kind of protein is haemoglobin?

Answer 1

Allosteric protein that displays cooperativity in oxygen binding and release

Question 2

Is the binding of oxygen by myoglobin cooperative?

Answer 2

No because it is a monomer (only one subunit)

Question 3

What is oxygen binding measured as a function of?

Answer 3

The partial pressure of oxygen

Question 4

What is the iron bound to in haemoglobin?

Answer 4

4 nitrogens

Question 5

What is the 5th coordination site of iron occupied by?

Answer 5

Imidazole ring of a histidine (proximal histidine)

Question 6

What binds to the 6th coordination site of iron?

Answer 6

Oxygen

Question 7

What happens to the iron when oxygen binds to it?

Answer 7

It moves into the plane of the protoporphyrin ring which pushes amino acids to different position

Question 8

What stabilises the bound oxygen?

Answer 8

The distal histadine

Question 9

Why can fMRI distinguish the relative amounts of oxy- and deoxyhemoglobin?

Answer 9

Because the magnetic properties of the heme iron changes when it moves into the plane of the protoporphyrin ring

Question 10

What is the concept called which makes heme have higher affinity for oxygen once one is bound?

Answer 10

Cooperativity

Question 11

What kind of oxygen binding curve does myoglobin display?

Answer 11

Hyperbolic

Question 12

What kind of oxygen binding curve does haemoglobin display?

Answer 12

Sigmoid curve which indicates that O2 binding and release is cooperative

Question 13

When partial pressure of oxygen decreases, what happens to the affinity?

Answer 13

It also decreases

Question 14

Is haemoglobin exposed to superoxide ions?

Answer 14

No

Question 15

Why is it critical that oxygen is only released in the O2 and not superoxide state?

Answer 15

Superoxide is very reactive and will bind and harm other molecules
Iron ion would be left in the ferric (Fe3+) state, preventing additional oxygen binding (Myoglobin in this state is called metmyoglobin)

Question 16

What is myoglobin called when iron ion is left in the ferric state (Fe3+), preventing additional oxygen binding?

Answer 16

Metmyoglobin

Question 17

What feature of myoglobin help prevent superoxide release?

Answer 17

Distal histidine which donate a hydrogen bond to the oxygen molecule

Question 18

What will exercise do to the partial pressure of oxygen in a tissue?

Answer 18

Oxygen will deplete so the partial pressure goes down in the tissue

Question 19

2 models that describe how haemoglobin goes from T state to R state?

Answer 19

Concerted model
Sequential model

Question 20

Which model is most likely? Concerted or sequential

Answer 20

Both, they most likely both happen

Question 21

Which interface is the structural changes at the heme groups transmitted to?

Answer 21

Alpha1 Beta2
Alpha2 Beta1

Question 22

Where do allosteric effector bind on haemoglobin?

Answer 22

At a site separate from the active site

Question 23

What is the activity of an allosteric protein regulated by?

Answer 23

Allosteric effectors

Question 24

What is oxygen? A homotropic of heterotrophic allostery?

Answer 24

Homotropic allosteric modulator because it is itself the ligand, not only a molecule that modifies the structure of haemoglobin but also the molecule that binds haemoglobin

Question 25

What is a homotropic allosteric effector?

Answer 25

A molecule that affects its own binding to the protein (at other site) Like how binding of O2 increases the affinity for binding on other side of Hb

Question 26

What os a heterotropic allosteric effector?

Answer 26

When the allosteric effector is different from the ligand whose binding is altered Like the effect og H+ on the P50 for oxygen binding

Question 27

What shift in the O2 binding curve do interactions with homotropic and heterotrophic allosteric effectors lead to?

Answer 27

Horizontal shifts

Question 28

Examples of homotropic allosteric effectors

Answer 28

CO2 2,3-bisphosphoglycerate H+

Question 29

Do heterotrophic allosteric effects increase or decrease the affinity for O2?

Answer 29

Decrease (thus deliver more oxygen to the tissue)

Question 30

What is 2,3-bisphosphoglycerate?

Answer 30

A byproduct of glycolysis Negatively charged small molecule which binds to the T-state and stabilises it by binding in positively charged pocket at the interface of each subunits (between the beta subunits)

Question 31

2 subunits does foetal haemoglobin not have?

Answer 31

The beta subunits

Question 32

2 subunits does foeatal haemoglobin have?

Answer 32

The gamma subunits

Question 33

What does the gamma subunit defer from the beta subunit?

Answer 33

1 amino acid

Question 34

Why does 2,3-bisphosphoglycerate not bind to foetal haemoglobin?

Answer 34

Because it has gamma subunits instead of beta subunits so no positively charged pocket

Question 35

At the same concentrations of 2,3-bisphosphoglycerate, which has a higher affinity for oxygen, maternal or foetal haemoglobin?

Answer 35

Foetal

Question 36

What is the role of distal histidine regularly?

Answer 36

Increases the affinity for oxygen by making the space better fit for oxygen by bending the angle of binding to fit oxygen's angle

Question 37

Why is CO so toxic?

Answer 37

Because it saturates the haemoglobin so oxygen can't bind and you die. It does so very quickly

Question 38

What does distal histidine do?

Answer 38

Keeps oxygen (and CO) at an angle

Question 39

What can destabilise the affinity for CO?

Answer 39

The distal histidine, but CO still binds better

Question 40

What does CO act as when bound to heme?

Answer 40

An irreversible ligand

Question 41

Is the affinity for O2 greater than CO?

Answer 41

No the affinity for CO is 2000 times greater

Question 42

What is hypoxia?

Answer 42

Low availability of oxygen in a tissuwe

Question 43

How does temperature effect the affinity for oxygen?

Answer 43

The higher the temperature the less affinity for oxygen

Question 44

Examples of hemoglobinopathies?

Answer 44

Sickle cell disease Thalassemia

Question 45

What are hemoglobinopathies?

Answer 45

Genetic disorder affecting the production or structure of haemoglobin molecule

Question 46

What gives sickle cell diseased RBC their sickle shape?

Answer 46

The fibers of haemoglobin being misshaped

Question 47

What is thalassemia caused by?

Answer 47

An imbalanced production of haemoglobin chains

Question 48

What is alpha-thalassemia?

Answer 48

When there is not enough alpha chains

Question 49

What can cytoglobin protect against?

Answer 49

Hypoxia

Question 50

What can glycated haemoglobin tell you about glucose levels?

Answer 50

Levels from the past 3 months

Question 51

Is the binding of oxygen in myoglobin cooperative?

Answer 51

No

Question 52

What forms the 5th coordination bond with iron?

Answer 52

Proximal histidine

Question 53

What forms the 6th coordination bond with iron?

Answer 53

Oxygen

Question 54

What happens to the magnetic properties of the heme iron when it moves into the plane of the protoporphyrin?

Answer 54

It changes

Question 55

Why can fMRI distinguish the relative amounts oxygenated and deoxygenated haemoglobin?

Answer 55

Because the properties of the heme iron changes

Question 56

2 reasons why it is critical that oxygen is released only in the oxygen and not the superoxide state

Answer 56

Superoxide is very reactive and can harm other cellular molecules The iron would be left in the ferric state, preventing it from binding additional oxygen

Question 57

What are the main factors that affect the binding of oxygen to haemoglobin?

Answer 57

pH CO2 2,3biphosphoglicerate

Question 58

Which way does the saturation curve shift when an allosteric effector is added?

Answer 58

To the right

Question 59

What does the shift to the right of the saturation curve indicate?

Answer 59

Decreased affinity for oxygen

Question 60

Which way does the saturation curve shift when an allosteric effector is removed?

Answer 60

To the left

Question 61

Does a decrease in pH increase or decrease the affinity for oxygen?

Answer 61

Decrease

Question 62

Is 2,3-bisphosphoglycerate a negative or positive regulator of haemoglobin?

Answer 62

Negative

Question 63

What is 2,3-bisphosphoglycerate produced from?

Answer 63

An intermediate in glycolysis

Question 64

Where on the haemoglobin does 2,3-bisphosphoglycerate bind?

Answer 64

The positively charged central cavity

Question 65

Why does the 2,3-bisphosphoglycerate bind to the positively charged cavity?

Answer 65

Because it is negatively charged because of the phosphate

Question 66

In which state of haemoglobin does 2,3-bisphosphoglycerate bind better?

Answer 66

T state because it is closed in R state

Question 67

What happens to oxygen delivery at high altitudes?

Answer 67

It declines by 1/4th to a max of 30%

Question 68

What does 2,3-bisphosphoglycerate facilitate?

Answer 68

Unloading of oxygen in tissues

Question 69

Where is the 2,3-bisphosphoglycerate in competition with oxygen for the binding site?

Answer 69

On the beta subunit

Question 70

Does fetal haemoglobin have a high or low 2,3-bisphosphoglycerate affinity?

Answer 70

Low

Question 71

What is the Bohr effect?

Answer 71

Carbon dioxide and H+ stimulating the release of oxygen

Question 72

Example of something that can induce the Bohr effect?

Answer 72

Lowering the pH as it decreases the affinity for oxygen

Question 73

Which amino acid is a big contributor to the Bohr effect?

Answer 73

His146 of the beta subunit

Question 74

Which enzyme catalyses the reaction of Oxygen binding by haemoglobin?

Answer 74

Carbonic anhydrase

Question 75

What is carbonic anhydrase important to keep constant?

Answer 75

pH

Question 76

How does CO2 effect eh affinity of haemoglobin to oxygen?

Answer 76

It decreases it

Question 77

2 signals to to haemoglobin that we need more oxygen

Answer 77

Release of hydrogen and 2,3-DPG

Question 78

In what form is 15-20% of CO2 exported?

Answer 78

Carbamate

Question 79

What does the formation of carbamate yield?

Answer 79

A proton and saltbridges

Question 80

How does the formation of carbamate contribute to the Bohr effect?

Answer 80

By yielding a proton

Question 81

How does the formation of carbamate stabilise the T state?

Answer 81

By forming additional salt bridges

Question 82

Which binds better, carbon monoxide or oxygen?

Answer 82

Carbon monoxide

Question 83

In what shape does carbon monoxide bind? Linear or bent?

Answer 83

Linear

Question 84

How does temperature affect the oxygen affinity?

Answer 84

Higher temperature means lower oxygen

Question 85

What are hemoglobinopathies?

Answer 85

Haemoglobin mutants

Question 86

What mutation causes sickle cell disease?

Answer 86

Substitution of Valine for glutamate

Question 87

When is sickle cell anaemia fetal?

Answer 87

When both alleles of the beta chain are mutated

Question 88

What does an individual with sickle cell disease present clinically?

Answer 88

Intermittent episodes of haemolytic anaemia resulting from chronic lysis of red cells and painful vasoocclusive crisis

Question 89

What kind of trait is sickle cell disease?

Answer 89

Heterozygous recessive

Question 90

What does it mean that haemoglobin can be glyciated?

Answer 90

That it can bind to glucose