Hemoglobin, Myoglobin and oxygen transport Flashcards
(127 cards)
1
Q
Functions of globular proteins (5)
A
Storage of ions and other molecules
Transport of Ions and molecules
Defense against pathogens
Muscle contraction
Biological catalyst
2
Q
Do proteins bind with ligands through irreversible reactions or reversible?
A
Reversible
3
Q
Are binding sites specific to each ligand?
A
Yes
4
Q
What is ligand binding coupled to conformational changes called?
A
Induced fit
5
Q
What is it called when conformational changes in one subunit can affect the others
A
Cooperativity
6
Q
Are the interactions in binding sites with ligand covalent bonds?
A
No, the bonds are non covalent
7
Q
Do ligands typically bind on the surface of a protein?
A
No they typically find their binding sites in cavities
8
Q
Model of specificity ligand binding?
A
Lock and key model
Induced fit
9
Q
What are the 4 characteristics of complementarity of the ligand and binding site?
A
Size
Shape
Charge
Hydrophobic/hydrophilic character
10
Q
What is induced fit?
A
When ligand bind to protein there is a conformational change
11
Q
What is lock and key?
A
Protein and ligand fit together perfectly
12
Q
What are interactions between ligand and protein mediated by?
A
Induced fit
13
Q
What can interactions between ligand and proteins regulated by?
A
Activator or inhibitor
14
Q
What are things that induce change in protein conformation called?
A
They are allosteric
15
Q
Can ligands help each other change the shape?
A
Yes it is comparitivity
16
Q
How many subunit are myoglobin?
A
1
17
Q
How many subunits are haemoglobin?
A
4
18
Q
How many alpha subunits in haemoglobin?
A
2
19
Q
How many beta subunits in haemoglobin?
A
2
20
Q
Do alpha and beta subunit in haemoglobin interact which each other across both alpha and beta and beta and beta and alpha and alpha?
A
They across with each other all permutations with different surfaces
21
Q
What is a dalton?
A
The weight of a hydrogen atom
22
Q
What is the kilodalton?
A
The standard unit used to represent the weight of large molecules such as proteins
23
Q
Where does haemoglobin have to pick up oxygen?
A
In a place with high partial pressure of oxygen
24
Q
Where does haemoglobin have to release oxygen?
A
In a place with low partial pressure of oxygen
25
What is the prostetic group of haemoglobin?
Heme
26
Do protein have a naturally affinity for oxygen?
No the need the prosthetic group heme to do so
27
What does myoglobin do?
Store oxygen
28
Where is myoglobin found?
In the muscles
29
How many helixes in myoglobin?
9 (labelled a-h)
30
Is Heme a ligand?
No it is a prosthetic group
31
What is responsible for the conformational change when the oxygen is bound? (haemoglobin and myoglobin)
The proximal and distal histidine
32
What are the two important histidines in haemoglobin and myoglobin? and what do they bind with?
Distal bind with oxygen and proximal bind with Iron
33
What part of the heme holds the central iron ion?
The porphyrin ring
34
Would the protein function without the prosthetic group?
No
35
What are the two confirmation of the heme?
Tense state and relaxed state
36
When is the tense state of heme?
No oxygen
37
When is the relaxed state of heme?
With oxygen
38
Does the other subunits change conformation when oxygen binds to one?
Yes
39
What happens to iron when oxygen bind?
Its pushed into the plane of the heme
40
Could myoglobin transport oxygen?
No it wouldn't be good because the partial pressure would have to be very low... So it would have problems releasing it
41
Does myoglobin bind well to oxygen at low partial pressure?
Yes
42
Where is CO2 bound in haemoglobin?
On the protein chains
43
Does pH change the affinity of binding with oxygen?
Yes
44
What is carbon monoxide for a heme?
Almost irreversible ligand
45
Does heme have a higher affinity for oxygen or carbon monoxide?
Carbon monoxide by A LOT (carbon monoxide poisoning)
46
Why can the affinity for oxygen change?
It's a multiple binding site and they interact with each other because of positive cooperativity
47
What is the main difference between fetal and adult haemoglobin?
Has higher affinity for oxygen because the nature of the exchange between mother and fetal
48
How many coordination bonds does iron have?
6
49
Does the magnetic properties change when the heme iron moves into the plane of the protoporphyrin?
Yes
50
Where does biphosphoglycerate come from?
Glycolosis
51
Where is the 2,3-bisphosphoglycerate found?
In the central cavity of haemoglobin
52
What is the Bohr effect?
When blood plasma pH decreases the haemoglobin has less affinity for O2
53
Which binds better to heme O2 or CO?
CO
54
How does the distal histadine effect the CO affinity of heme?
Makes it less
55
What is hypoxia?
Low availability of O2 in a tissue
56
How does sickle cell disease effect your chances of malaria?
Lowers the chances
57
What does the non covalent binding of ligand to binding site ensure?
That the binding is reversible
58
Are the interactions between ligand and protein strong or weak?
Weak
59
What does it mean when 2 ligands bind cooperatively to a protein?
When the ligands help eachother to bind to the protein
60
What is induced fit mediated by?
Weak interactions
61
What is an allosteric?
Anything that induces changes in the conformation of proteins
62
Can humans transport oxygen as is?
No we need facilitation for transporting it
63
2 main proteins in red blood cells
Hemoglobin
Carbonic anhydras
64
What stores oxygen in the tissues?
Myoglobin
65
What transports oxygen in the blood?
Haemoglobin
66
Which is the standard unit to measure proteins in?
Kilodalton
67
What is a prosthetic group on of proteins?
A non amino acid component
68
Ferrous state of iron
Fe2+
69
Ferric state of iron?
Fe3+
70
In which state of iron does oxygen bind?
Ferrous
71
What does heme bind better, oxygen or monoxide?
Monoxide
72
What is the amount of O2 in solution directly proportional to?
The partial pressure
73
What is the prosthetic group of haemoglobin?
Heme
74
Which proteins are oxygen binding?
Globins
75
What would happen if transitions metals bind O2 while free in solution?
They would form free radicals
76
How many oxygen molecules can haemoglobin bind?
4
77
How many oxygen molecules can myoglobin bind?
1
78
What are the interactions between the subunits in haemoglobin?
Hydrophobic
Hydrogen bond interactions
79
How much of the total blood transported in blood is bound by haemoglobin?
98%
80
How many coordinate binding does the iron in heme have?
6
81
Where does iron bind in heme?
4 bonds with nitrogen of the porphyrin rings
1 bond with proximal histidine
1 bond with oxygen
82
What happens if iron is not ferrous?
If there is a reduction you can have a super oxide which is a reactive oxygen species which is extremely toxic
83
Mechanism of cooperative in haemoglobin
When oxygen binds to heme it causes a conformational change that are relevant to the structure and function of haemoglobin
84
Which state is haemoglobin in when the blood is in the lungs?
Relaxed because the oxygen concentration is high
85
Which state is haemoglobin in when the blood is in the tissue?
Tense because the oxygen concentration is low
86
What allows the haemoglobin to release oxygen in the tissue when needed?
The tense state
87
What happens to the position of the iron when oxygen is added?
It is changed which transmit a change to the histidine and the rest of the subunits
88
What does the position of the iron change to when oxygen is added?
It is moved to be planar with porphyrin
89
Shape of heme before oxygen binds
Domed (nonplanar)
90
Shape of heme after oxygen binds
Planar
91
What pulls iron out of plane?
The proximal histidine
92
What does the concerted model theorise that happens when one oxygen molecule binds?
The change is transferred to all other subunits (all or nothing model)
93
What does the sequential model theorise that happens when one oxygen molecule binds?
The change happens step for step
94
Is the structure of heme the same in myoglobin and haemoglobin?
Yes
95
Why would myoglobin be a bad oxygen transporter?
Because it has problems releasing the oxygen
96
What is the X axis in a saturation curve?
pO2 (kPa)
97
What is the Y axis in a saturation curve
Saturation index (0 is no oxygen bound, 1 is 100% oxygen bound)
98
What kind of shape is the haemoglobin saturation curve?
Sigmoid
99
What kind of shape is the myoglobin saturation curve?
Hyperbolic
100
What does the sigmoid curve indicate?
Cooperativity
101
When is myoglobin used?
When the concentration of oxygen in muscles is very low
102
Does changes in pH have an effect on binding of oxygen in haemoglobin?
Yes
103
At what pH is haemoglobin affinity for oxygen lower?
At lower pH
104
What is positive cooperativity?
First binding event increases affinity at remaining sites (sigmoid curve)
105
What is negative cooperativity?
First binding event reduces affinity at remaining sites
106
How is the haemoglobin in the foetus different?
It has 2 alpha subunits and 2 gamma chains
It tends to keep the oxygen and not release it
107
How is the binding curve of a foetus?
Less sigmoidal as it doesn't need to release the oxygen
108
2 models of cooperativity
Concerted
Sequential
109
Which model of cooperativity is all or nothing?
Concerted
110
Which model of cooperativity is step for step?
Sequential
111
When is allosteric regulation homotropic?
When the ligand is also the allosteric regulator
112
When is the allosteric regulation heterotrophic?
When the ligand and the allosteric regulator are 2 different molecules
113
Is the allosteric regulation of haemoglobin homotropic or heterotrophic?
Homotropic
114
Which state of haemoglobin is more stable?
T sate
115
Which state of haemoglobin has more interactions?
T state
116
What does the binding of oxygen trigger a conformational change from and to?
From T to R
117
Where is the ion pairs that are broken when haemoglobin change from T to R state found?
Between the alpha1 and beta2 interface
118
Are the non covalent bonds in deoxygenated and oxygenated haemoglobin the same?
No they differ
119
Why do deoxygenated and oxygenated haemoglobin have different non covalent bonds?
Because the amino acids that interact and bind in them are different
120
Why does fetal haemoglobin have a higher affinity for oxygen?
Because beta chains are substituted for gamma chains
121
What is the difference between the beta and gamma chains in haemoglobin?
In position 143 gamma chains have Serine residue while beta has histidine residue
122
Which has a higher affinity for oxygen, fetal or adult haemoglobin?
Fetal
123
What does the fact that the foetus can stay without oxygen for longer make it resistant to?
Hypoxia
124
What ensures that the oxygen is transferred to the foetus from the maternal blood across the placenta?
The fact that it has a higher affinity for oxygen
124
Why is the PO2 in fetal tissue very low?
Because of the high metabolic rate associated with fetal growth rates
125
When is the fetal haemoglobin replaced with adult haemoglobin?
At birth
125
