Chapter 7 Key Terms and concepts

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deoxymyoglobin
oxygen free form
oxymyglobin
an oxygen molecule is bound
the ability of myoglobin and hemoglobin to bind oxygen depends on the presence of a...
bound prosthetic group called heme.
Consists of an organic component and a central iron atom
metmyoglobin
does not bind oxygen. Potential oxygen storage capacity is lost
hemoglobin interacts with _____ a molecule that significantly lowers hemoglobins oxygen affinity
2,3 - bisphosphoglycerate
What does a sigmoid binding curve suggest about hemoglobin?
the binding of oxygen at one site within the hemoglobin tertramer increases the likelihood that oxygen binds at the remaining unoccupied sites
Hemoglobin undergoes substantial changes in Quaternary structure on oxygen binding:
the albl and a2b2 dimers rotate approximately 15 degrees with respect to one another
the Quaternary structure observed in the deoxy form of hemoglobin, deoxyhemoglobin, is often referred to as
T (tense) state because it is quite constrained by subunit - subunit interaction
the Quaternary structure of the fully oxygenated form, oxyhemoglobin, is referred to as the
R (relaxed) state. Binding sites are free of strain and are capable of binding oxygen with higher affinity than those that are in T state
Concerted model (MWC)
Hemoglobin can only exist in two forms: the T state and the R State. As a hemoglobin tetramer binds each oxygen molecule, the probability that the tetramer is in the R state increases.
Sequential model
the binding
of a ligand to one site in an assembly increases the binding affinity of
neighboring sites without inducing a full conversion from the T into the R
state
An additional mechanism is needed to properly stabilize the T state
2,3 -BPG
T to R transition in the presence of 2,3 -BPG
On T to R transition the pocket that was created when BPG binds in the center of the tetramer collapses.

When 2,3 -BPG is present more oxygen binding sites within the hemoglobin tetramer must be occupied in order to induce the T to R transition
How can Carbon monoxide disrupt oxygen transport of hemoglobin?
First carbon monoxide binds to hemoglobin more tightly than oxygen.
Carbon monoxide will displace oxygen from hemoglobin, preventing its delivery.

Second, carbon monoxide bound to one site in Hb will shift the oxygen saturation curve of the remaining sites to the left, forcing tetramer into the R state
How does carbon dioxide stimulate the release of oxygen?
First, the presence of high concentrations of carbon dioxide leads to a drop in pH, H2CO3 formed.

H2CO3 dissociates into HCO3- and H+ resulting in a drop of pH that stabilizes the T state.

Second, a direct chemical interaction between carbon dioxide and hemoglobin stimulates oxygen release.
Describe the Bohr effect
At lower pH hb affinity for O2 goes down.

High CO2 levels lead to decreased affinity of Hb for O2.

At low pH, there is added proton that stabilizes the salt bridge and the T state of Hb.
what happens if there is no 2,3 -BPG with Hb?
The Hb will be in an R state: tight binding of O2
what direction on an oxygen affinity graph would indicate a decrease in oxygen affinity? increase?
Decrease or lower affinity for O2 would shift Hb to the right.
Increase or higher affinity for O2 would shift hB to the left
allosteric effector
does not bind in active site, but affects activity
what is the difference between fetal and maternal Hb?
Fetal Hb is a2y2 in which a histindine on both y is replaced with serine.
Maternal Hb is a2B2
Fetal Hb has a higher affinity for oxygen
working at high altitudes the concentration (2,3 - BPG) in red blood cells increases. What effect would this have on oxygen binding curve for Hb? why would this adaptation be beneficial for functioning well at high altitude?
Higher concentration of 2,3 - BPG would shift oxygen - binding curve to the right, causing an increase in P50. The larger value of P50 would promote dissociation of oxygen delivered to the tissues.
what percentage of oxygen does Hb allow to release? why is Mb a poor oxygen transporter?
Hb releases 66% of oxygen at physiological conditions. Mb is a poor oxygen transporter because it binds tightly to oxygen
what is myoglobin?
myoglobin is a monomer with one O2 binding heme group
what is the structure of myoglobin?
myoglobin's structure shows alpha helices connected by turns
what is a heme?
"heme" is the whole group with iron. "porphryn" is the organic component
Where is Fe2+ located when oxygen is not bond in deoxyhemoglobin?
Outside of the plane of the proximal histidine
How does Hb bind cooperatively?
The actual site in Hb are too far apart to have direct interaction with each other. So there are indirect interactions: the quaternary structure of Hb changes upon O2 binding
what is the purpose of the distal histidine?
Prevents super oxides from forming
what is the purpose of the proximal histidine?
To provide support?
what would happen if Hb was constantly in the R state? T state?
If constantly in the R state, the oxygen saturation curve would look similar to myoglobin and be pushed to the left.
If constantly in the T state, would have a linear oxygen saturation curve (similar to noncooperative protein)
A hemoglobin has been mutated and no longer properly releases oxygen but instead binds tightly. What has likely occurred?
The hemoglobin has lost its Quaternary structure
when referring to an oxygen - binding curve what does p50 refer to? what is the p50 of myoglobin? Hb?
p50 refers to half saturation of binding sites
myoglobin = p50 at 2
Hb = p50 at 26
why is hemoglobin's binding behavior referred to as cooperative?
Because the binding of oxygen at one site within the Hb tetramer increases the likelihood that oxygen binds at the remaining unoccupied sites
what percentage of sites contribute to oxygen transport in myoglobin? Hb? non cooperative protein?
myoglobin: 7%
Hemoglobin: 66%
non cooperative protein: 38%
Explain the interaction between 2,3 -BPG and Hb
A single molecule of 2,3 -BPG binds in the center of the tetramer, in a pocket present only in the T form.

On T to R transition, this pocket collapses and the 2,3 -BPG is releases
How is carbamate's role in the release of oxygen from Hb?
Carbon dioxdie stabilizes deoxyhemoglobin by reacting with the terminal amino group to form carbamate groups, which are negatively charged.

These negatively charged carbamate groups participate in salt - bridge interactions that stabilize the T state, favoring the release of oxygen
Explain how HCO3- is formed and where it ends up?
Most of the carbon dioxide released from red blood cells is transported to the lungs in the form of HCO3-. Much of the HCO3- that is formed leaves the cell through a specific membrane transport protein that exchanges HCO3- from one side of the membrane for Cl- from the other side. HCO3- in the lungs is converted back into carbon dioxide and exhaled.
why does iron sit on the outside of the porphryin until oxygen binds?
Because of partial electron transfer from the iron to the oxygen, the iron ion moves into the plan of the porphyrin on oxygen binding
which amino acid stabilizes the Fe group in the heme?
Histidine
If the hill coefficient is n> 1 what does this tell you about the binding of oxygen in hemoglobin?
This tells you that oxygen binding is cooperative, if it was n=1 this would tell you it was independent
what best describes how 2,3 -BPG reduces Hb affinity for oxygen?
The 2,3-BPG is highly negatively-charged and forms salt bridges with positively-charged His and Lys in the central cavity of the hemoglobin molecule. It binds with high affinity to the deoxygenated state and thus stabilizes the T state. When oxygen binds, conformational changes occur that reduce the size of this central cavity, essentially "kicking out" the 2,3-BPG.
In fetal hemoglobin (HbF), the two β subunits are replaced with two γ subunits, resulting in fetal hemoglobin having a higher affinity for oxygen than the mother's normal adult hemoglobin has. This increased oxygen affinity of HbF is due to
The decreased affinity for 2,3-BPG makes the binding of oxygen more favorable in HbF
The molecular consequences of the hemoglobin S mutation are that
the hemoglobin S forms aggregates and fibrous precipitates when oxygen is released.
Hemoglobin S, the abnormal form of hemoglobin responsible for sickle cell anemia, is the result of a mutation in the gene for the β subunit. This mutation results in the change of
a negatively charged amino acid R group to a hydrophobic amino acid R group.
Hemoglobin consists of four polypeptide chains, two identical alpha chains and two identical beta chains. Each of the subunits consists of a set of alpha helices in the same arrangement as the alpha helices in myoglobin. What is this recurring structure called?
Globin Fold
2,3 - BPG is an allosteric effector of hemoglobin that binds to sites on the molecule that are distinct from oxygen - binding sites. Under the Bohr effect what other two allosteric effectors bind hemoglobin?
hydrogen ions and carbon dioxide
what would happen if the binding site for 2,3 -BPG due to mutation was moved to the outside of hemoglobin instead of the usual center?
The electrostatic interaction between BPG and hemoglobin would weaken by competition with water molecules. The T state would not be stabilized
What would happen to proximal histidine if it were mutated?
Lose Fe
What would happen to distal histidine if it were mutated?
Would get superoxidie
Why would it be that the pH in the lungs is higher then the pH of tissues?
Because the lungs is where hemoglobin is having oxygen bind to it where it transitions from the T to R state. Tissues is where hemoglobin needs to transport oxygen and transition back to the T state. An increase in pH causes an increase in the affinity for oxygen or a left shift on the oxygen saturation curve. By having the pH decrease or having it lower in the lungs according to Bohr's law shifts the oxygen binding curve to the right allows hemoglobin to release oxygen.
what causes sickly cell anemia?
a mutation in the Beta Chain, a Glu is replaced with a Val
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