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54 Cards in this Set
- Front
- Back
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What percentage of hemoglobin's oxygen carrying capacity is used?
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90% (myoglobin would be 7%)
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Sickle Cell anemia is caused by 1 amino acid change in what protein?
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hemoglobin
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what is the main structural component of myoglobin discovered in the spemr whale?
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alpha helices connected by turns.
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What is the organic component of the heme prostethic group?
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protoporphyrin made up of four pyurole rings connected by methine bridges.
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what is the normal oxidation staate of iron in heme?
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+2
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How many coordination sites does Iron have? What occupies these sites?
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6
4 are pyrole rings. 1 is the proximal histidine 1 is an oxygen binding site. |
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Does the iron atom lie within the porphyrin plane?
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no it lies .4 A outside of the plane. It is stabilized outside by the proximal histidine. to allow for oxygen to bind within the site. Additionally, Iron cannot fit in the space provded by the plane.
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a heme with Fe3+ is called what? Why is it significant
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metmyoglobin. It does not bind oxygen.
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Wy must oxygen leave as O2 rather than O2- the superoxide ion which is resides in the heme as?
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Superoxide can react with the body and cause damage. It also leaves iron in the metmyoglobin state which can no longer bind oxygen.
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When oxygen is bound, what state is iron in?
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3+ (ferric)
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Besides iron, what stabilized the bound oxygen (and leads to a conformational change?)
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Distal histidine (donates an H bond)
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does the superoxide form of oxygen stabilize or weaken its association with heme.
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It strengthens. Thus pulling the molecule tighter and inducing the conformational change.
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What four subunits compose a hemoglobin molecule?
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2 alpha and 2 beta
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Globin fold
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recurring structure of alpha helices seen in both myuoglobin and hemoglobin
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How many iron atoms are present in hemoglobin? Myoglobin?
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4 and 1 respectively.
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Oxygen Binding curve
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Compares oxygen binding properties of proteins.
A plot of fractional saturation vs oxygen concentration |
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what metric defines concentration of oxygen?
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Partial pressure.
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is oxygen binding stronger or weaker in hemoglobin than myoglobin
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hemoglobin binding is weaker than myoglobin.
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what does the sigmoid binding curve represent?
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cooperative binding
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2,3 bisphosphoglycerate does what to the oxygen binding capability of Hemoglobin?
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it weakens it, thus allowing a release of oxygen.
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what is the partial pressure of oxygen in the lungs?
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100 torr
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What is the patial pressure of oxygen in the tissues?
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20 torr
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Compare the oxygen delivery of hemoglobin, non-cooperative hemoglobin, and myoglobin
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66% 38% 7% respectively
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Resting muscle has a pO2 of ____ torr. This results in what percentage of oxygen delivery.
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40 torr roughly 21%
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What is the difference in oxygen delivery between exercising muscle and resting muscle.
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exercising = 66% resting = 21%
difference = 45% |
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the unbound state is called the ___ state
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T for tense
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The bound state is called the ___ state.
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R for relaxed.
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describe geometrically the T-state binding curve.
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linear with much less binding capability then the permanent R state and the sigmoid cooperative transition plot.
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Differentiate the concerted model and the sequential model of the T vs R state configuration.
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In the concerted model, all sites are either T or R state. The Probability of the sites being R is dependent on the number of bound oxygens.
In the sequential model, each site can induce a conformational chang eon a neighboring site. and sites conform individually. |
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What particularly structure leads to conformational change upon oxygen binding.
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The binding of O2 causes the iron atom to be pulled into the place of the heme group. This pulls the proximal histidine and its corresponding alpha helix into the center of the molecule and induces a change in its neighboring subunit.
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How does the binding of pure hemoglobin compare with hemoglobin in red blood cells? Why?
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Pure hemoglobin binds tighter because there is no 2,3BPG to reduce the binding affinity. Additionally pH plays a role.
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without 2,3 BPG what would be the oxygen delivery of hemoglobin?
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around 8%
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where and when does 2,3 BPG bind to hemoglobin.
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In the center of the tetramer only in the T-State.
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allosteric effector.
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an effector that binds to a different site than the target molecule.
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Why is fetal hemoglobin a stronger binder of oxygen than adult hemoglobin?
Why is this important? |
fetal hemoglobin has 2 less positive charges in the 2,3 BPG binding site. Therefore there is less 2,3 BPG binding and more ability to enter the R state.
This is important as the babies blood needs to suck out as much o2 form the mothers system as possible. |
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How do hydrogen ions and carbon dioxide effect oxygen binding of hemoglobin?
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allosteric effectors which reduce binding.
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Bohr Effect
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Reduction of binding affinity via carbon dioxide and hydrogen ions.
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as pH increases... how is oxygen binding affinity affected.
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It is increased (higher pH means less hydrogen ions)
(This is the only left shift) |
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how does pH effect oxygen affinity.
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lower pH results in higher proton concentration which forms salt bridges which stabilize the T state.
histidine B146 is a big one. |
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high concentrations of CO2 in the blood cell causes what chang ein pH
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lowers pH
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what enzyme creates an acidic environment in response to increased CO2
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carbonic anhydrase.
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how does carbon dioxide stabilize deoxyhemoglobin?
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reacts with terminal amino groups to form carbamate groups. These negatively charged groups create salt bridges between termini of the ab dimers.
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how is CO2 transported to the lungs.
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as the bicarbonate ion HCO3-
A special transporter trades HCO3- for Cl- ions. |
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What do the lungs do with HCO3-
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converts it back to CO2 and water.
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What residue is affected in sickle cell anemia?
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a substitution of position 6 in the beta chain. Valine was substituted for glutamate. This replaced a negatively charged molecule with a neutral amino acid. greatly affecting structure.
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how does the sickle cell mutation affect hemoglobin.
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it reduces solubility of deoxyhemoglobin, but does not appreciably affect oxyhemoglobin.
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why is oxygenated hemoglobin unaffected by sickle cell anemia?
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Because the 6 postiion valine interacts with 85 Phe and Val 88 of a neighboring B chain. In the oxygenated form, Phe 85 and Val 88 are buried within the molecule.
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why is the sickle cell allele so conserved?
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because of the malarial resistance of carriers.
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Why is b-thallesemia bad?
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in b thallesemia the beta chain is not prduced sufficiently. Thsi results in alpha chain aggregates that precipitate and damage immature blood cells.
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Why is alpha thallesemia bad
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In a thallesemia the alpha chain is not produced and tetramers of beta chains exist which bind oxygen too tightly, resulting in reduced transport of oxygen.
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since there are 4 genes for the alpha chain and only 2 for the beta chain? why do the excess alpha chains not aggregate and precipitate?
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a hemoglobin stabilizing protein (AHSP) is soluble.
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When a-hemoglobin has AHSP bound, what is different about iron binding?
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the iron is bound to the distal histidine rather than the proximal histidine.
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What happens to AHSP bound alpha hemoglobin when b hemoglobin chains are formed?
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the ab dimer is preferred and AHSP is released to dissolve more alpha chains.
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name the two additional globins and their characteristics
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neuroglobin and cytoglobin. Both are monomeric. Both also have both histidines bound to iron. Additonal functions are unknown currently.
neuroglobin is specific to the brain and retina cytoglobin is located around the body. |
