2401- Biochemistry I, II, III Flashcards
Give the characteristics of myoglobin.
1 subgroup and 1 heme group
Proximal residue to heme- His F8 or His93
Has one binding site for O2
Made of of 8 helices, E, and G
Found in sketetal and cardiac muscle
Functions well for O2 storage
One heme group attached to its globin structure.
What is the state of iron in deoxymyoglobin?
Ferrous (Fe2+)
At which site does O2 bind to in the hemoglobin structure, “The Globin Fold”?
Distal histidine, E7
It establishes a hydrogen bond with O2 and plays an important physiological role in discriminating between ligands.
As it relates to the binding curves of myoglobin and hemoglobin, what is the significance of both curves?
Myoglobin has a high affinity for O2, therefore, at low PO2, its affinity would be greater to hemoglobin
Hemoglobin has a lower affinity to O2, thus as low levels the affinity would be less than to myoglobin.
At high PO2, both hemoglobin and my goblin would have similar affinities.
In the myoglobin molecule, what is the heme group bound in? And what is the residue?
E, F and G helices hydrophobic pocket
- His F8 (His93)
State the reason why deoxymyoglobin is unable to fit in the porphyrin plane (ring) whiles oxymyoglobin is able to fit in the plane.
Deoxymyoglobin has a higher spin (5 coordinate structure) Fe2+ therefore, it will sit above the plane.
Oxymyoglobin is a low spin (6 coordinate structure) with Fe2+ and Fe3+, the iron moves into the plane.
What stops the oxidation of Fe2+ to Fe3+ in a heme-containing protein?
The sequestering of each heme within the protein structure.
This restricts access to the two open coordination bonds.
Which structure binds at the following sites of hemoglobin:
A) proximal
B) distal
A) Nitrogren atom and residue of heme, histane F8 or His93
B) O2, Histane E7 which is formed by a H2 bond.
In which part of the body is does hemoglobin have a high affinity for O2?
Lungs.
Myoglobin has a greater affinity of O2 where?
Tissues where PO2 is low.
Give the characteristics of hemoglobin.
4 subgroups, 4 heme groups
A2b2
Multiple O2 binding sites
Functions better for O2 transport
What molecule stabilizes the following states of hemoglobin:
A) R state
B) T state
A) O2 stabilizes the R state of hemoglobin
B) 2,3- BPG, H+, CO2 stabilize the T state
A) when o2 is absent the T state is stabilize forming deoxymyoglobin
B) If the following is absent the R state is stabilized.
Describe allosteric proteins.
It is one where the binding of a ligand to one site affects another binding site on the same protein.
O2 is an example. Acts as a ligand and a homotropic modulator
Describe the Bohr Effect.
Is the effect of pH and CO2 on the release of oxygen by hemoglobin.
In the lungs, an increase in pH and low CO2 levels leads to an increase in the affinity of O2. Hemoglobin binds to O2 and releases H+
In the tissues, a decrease in pH (increase in H+) and high CO2 levels leads to a decrease in the affinity of O2. H+ is bound and O2 is released.
Explain how CO2 and O2 can effect the binding of each on hemoglobin.
When a higher level of CO2 is present in the tissues, hemoglobin binds to CO2 and the affinity for O2 decreases. When O2 becomes a greater concentration, hemoglobin binds to O2 and the affinity for CO2 decreases.
Give the effect of 2,3-BPG on hemoglobin.
- Decreases the affinity of hemoglobin to O2
- Stabilizes the T state of hemoglobin
- Binds to the cavity between the B subunits in T state
Only one molecule of 2,3-BPG is bound to hemoglobin.
How does 2,3-BPG and the affinity of O2 affect fetal hemoglobin?
Fetal hemoglobin has a greater affinity for O2 than adult hemoglobin.
Fetal hemoglobin has a even less affinity for 2,3 BPG
Based on cooperativity, describe how oxygen binds to hemoglobin.
- When O2 binds to hemoglobin at the 1st subunit, it will bind in a weak T state.
- Once bind, conformational changes occur allowing hemoglobin to go from a T to R state making easier for additional O2 molecules to bind.
- As oxygen continue to bind, the affinity would be greater until down to the last (4th) subunit where R state is strongly favored.
State the effects of CTP and ATP on ATCase kinetics.
A) CTP acts as an inhibitor, binds and activates the T state of a molecule. It decreases catalytic rate and has a low affinity.
B) ATP acts as an activator, binds and activates the R state. It has an increases catalytic rate and has a high affinity.
Discuss the affinity of O2 in hemoglobin in the lungs and tissues.
In the lungs, there is a greater affinity for O2 therefore, Hemoglobin holds on to O2 and releases H.
In tissues where there is a low O2 concentration, hemoglobin has a lower affinity therefore it releases O2 resulting in a net transfer of O2 to myoglobin.
What role does pH play in the Bohr Effect?
Acts as a allosteric inhibitor
Describe the haldane effect.
Describe the how the affinity of hemoglobin for H+ and CO2 is affected by changes in the Hb- O2 saturation.
State the equations for the following:
A) Bohr Effect
B) Haldane Effect
C) Bohr and Haldane effect
A) -🔺logP50/🔺pH
B) 🔺H+
C) (logPO2/pH)Y= (H+/Y)pH
List the following a- thalassemias:
A) normal
B) silent
B) thalassemias trait
D) Hemoglobin H disease
E) Hydrops fetalis
A) aa/aa
B) aa/a-
C) aa/- -
D) a-/- -
E) - -/ - -
List the following b- thalassemias:
A) normal
B) thalassemias trait or minor
C) thalassemia major, Cooley’s anemia or Mediterranean anemia
A) b/b
B) b/-
C) -/-
Which amino acid residues are involved in the salt bridges that stabilize the T state of hemoglobin?
A- lysine40
B- histidane 146
B- aspartate 94
In the R state, B-his146 deprotonates and is unable to form the His-positioning salt bridge. This means that for the interchain salt bridge in R, His is too far
How does carbon monoxide (CO) bind to hemoglobin?
It displaces weakly bound water and histidine in the 6th coordination slot of the iron ion.
What is the state of the iron ion in deoxyhemoglobin and oxyhemoglobin.
Deoxy- ferrous state (Fe2+)
Oxy - Ferric state (Fe3+)
State what does the following imply about ligand binding:
A) nH= 1
B) nH= >1
C) nH = <1
A) no cooperativity ; binding is independent
B) + cooperativity
C) - cooperativity