chapter 10- hemoglobin and myoglobin Flashcards
is the heme group conjugated or un-conjugated?
conjugated
hemoglobin contains how many heme groups?
four; one on each of the sub units
myoglobin contains how many heme groups?
One
molecular oxygen binds how to the Fe(II) atom in heme?
irreversibly
Heme is composed of an organic _____ and a ____ atom
an organic protoporphyrin and a metal atom
How many oxygen molecules does myglobin bind to reversibly?
One
How many oxygen molecules does hemoglobin bind to reversibly
four
hemoglobin is used to transport oxygen over _____ distances such as from the ______ to the _______
large distances such as from the lungs to all tissues
Myoglobin is used to transport oxygen over_____ distances such as ______ and behaves as _______
over short distances such as in the muscles and behaves as local “storage” reservoir of oxygen.
heme is what type of group
prosthetic group which contains a central iron atom
Each iron atom can form ____ coordination bonds
six coordination bonds
How many of iron’s bonds are with oxygen?
one of six of iron’s bonds are with oxygen
A heme group contains 4_____ that are liked via _____
pyrrole rings linked via methene (methine) bridges.
The T state of hemoglobin has _____ affinity for oxygen than R state because ______
T state has lower oxygen affinity than R state because the Fe-Nporphyrin bonds are longer
The fifth bond of iron in the heme group forms with ______
an imidazole ring of a histidine
The prosthetic group of hemoglobin and myoglobin is ______
heme
The organic ring component of heme is _____
porphyrin
Under normal conditions the central atom of heme is
Fe2+
How many bonds does the iron of heme have to the nitrogen in the porphyrin?
four
The iron of heme has _____ bonds. What are these bonds to?
4 to nitrogen in porphyrin
1 to oxygen
1 to imidazole ring of histidine
In deoxyhemoglobin the central atom is what?
displaced 4 A out of the plane of the porpyhrin ring system.
Does hemoglobin of myoglobin have a higher oxygen affinity?
Myoglobin
Which molecule (hemoglobin or myoglobin) delivers oxygen more efficiently to tissues?
hemoglobin
The binding pattern of hemoglobin is considered (cooperative or uncooperative)
cooperative
As oxygen binds to hemoglobin what happens to the molecule?
It changes the shape of the molecule, further enhancing oxygen binding
what is the shape of the oxygen dissociation curve of the Hemoglobin?
Sigmoidal in shape (“S”-shaped)
What shape is the dissociation curve for myoglobin?
hyperbolic
To what molecule (hemoglobin or myoglobin) does oxygen bind irreversibly?
neither
To what molecule (hemoglobin or myoglobin) does carbon monoxide bind at an allosteric site, lowering oxygen binding affinity?
Neither
The graph of the hill plot has an x-axis of ______ and a y-axis of ______
x-axis of log (pO2)
y-axis of log ((Yo2)/(1-Yo2))
In the hill plot if n is >1 than ______
oxygen binding is positively cooperative
In the hill plot if n = 1 than _____
oxygen binding is cooperative
In the hill plot if n is < 1 than ____
oxygen binding is negatively cooperative
When oxygen binds to hemoglobin it causes a ________ that breaks _____, lowering _____ of _____ which where involved in ______.
causes a conformation change that breaks several salt bridges, lowering pka of the basic amino acids involved in the salt bridges.
Oxyhemoglobin can be a simple buffer at a pka of ____; what is this equation?
6.7;
HHbO2 (H+) + HbO2
deoxyhemoglobin can be a simple buffer at a pka of ____; what is this equation?
7.8;
HHb (H+) + Hb
Oxyhemoglobin and deoxyhemoglobin can act as a simple buffer as a result of what?
oxygen binds to hemoglobin salt bridges to break lowering the pka of the basic amino acids involved in the salt bridges.
The inverse relationship between the binding H+ and O2 is the ______
Bohr effect
The Bohr effect does what?
helps maintain a constant blood pH as CO2 is converted to HCO3- in tissues and as HCO3- is converted back to CO2 in the lungs.
The O2 _____ in the lungs leads to the ______(release/uptake) of H+
binding in the lungs leads to the release of H+
The O2 _____ in the tissues leads to the _____ (release/uptake) of H+
release in the tissues leads to the uptake of H+
deoxyhemoglobin is responsible for protein ______ in the _____when pH is _____
protein binding in the tissues when pH is more than 7.4
oxyhemoglobin is responsible for protein _____ in the ______ when pH is ____
protein dissociation in the lungs when pH is less than 7.4
At a pH of _____ oxygen _____ occurs in the lungs which leads to_____
at a pH of 7.4 oxygen binding occurs which leads to a decrease in pH (not of the blood) and leads to oxyhemoglobin protein dissociation in the lungs.
At a pH of _____ oxygen ______ occurs in the tissue which leads to _______
at a pH of 7.4 oxygen dissociation occurs in the lungs leading to an increase in pH and leads to protein binding of deoxyhemoglobin in the tissues.
If the adult hemoglobin (HbA) is replaced by an infant’s fetal hemoglobin what would be expected to occur?
There will be a shift to the left of the hemoglobin curve meaning that at a given pO2 there will be a higher fraction of occupied binding sites.
What does a leftward shift of the hemoglobin curve indicate?
That at a given pO2 there will be an increase in the fraction of occupied binding sites.
Since the replacement of adult hemoglobin(HbA) with infant’s fetal hemoglobin causes a ____ curve shift which indicates what?
causes a leftward curve shift which indicates that infant’s fetal hemoglobin has a higher fraction of occupied binding sites than adult hemoglobin (HbA) at a given pO2.
If hemoglobin is isolated from RBC and stripped of 2,3-bisphosphoglycerate what would be expected to occur?
There will be a leftward shift of the hemoglobin curve meaning that at a given pO2 there will be a higher fraction of occupied binding sites.
Since the removal of 2,3-bisphosphoglycerate from hemoglobin causes a _____ this indicates what?
causes a leftward hemoglobin curve shift which indicates that 2,3-bisphosoglycerate decreases the affinity oxygen binding to hemoglobin since when it is removed hemoglobin has a higher fraction of occupied binding sites at a given PO2.
If Tetrameric hemoglobin is dissociated into its subunits causes a ______ meaning ______.
leftward shift in the hemoglobin curve meaning that at a given pO2 the fraction of occupied binding sites of hemoglobin increases when it is dissociated into its subunits.
What does a rightward shift of the hemoglobin curve indicate?
It indicates that at a given pO2 the fraction of occupied binding sites decreases (thus affinity decreases)
If the blood pH drops from 7.4 to 7.2 this causes what to happen to the hemoglobin curve?
A rightward shift indicating that the blood now has a decreased infinity for binding oxygen; a decrease in fraction of occupied binding sites at a given pO2.
If the CO2 concentration in the blood increases this causes what to happen to the hemoglobin curve?
A rightward shift of the hemoglobin curve meaning the affinity of oxygen for hemoglobin has decreased; at a given pO2 the fraction of occupied binding sites has decreased
Since a decrease in blood pH caused a ____ shift in the hemoglobin graph this indicates _____
rightward shift in the hemoglobin curve indicates that pH decreases the affinity of oxygen to hemoglobin
Since the increase in concentration causes a ____ shift in the hemoglobin graph this indicates ______
Rightward shift in the hemoglobin curve this indicates that an increase in concentration decreases the affinity of oxygen to hemoglobin .
If the concentration of 2,3 -bisphosphosphoglycerate increases during the acclimation to high altitudes this causes a ______ to happen to the hemoglobin shift
Causes a rightward shift of the hemoglobin curve. Meaning that it decreases the affinity of oxygen binding to hemoglobin; at a given pO2 the occupied binding sites has decreased.
Since an increase of 2,3- bisphosphosphoglycerate causes a ______ to occur this indicates that….
causes a rightward curve shift of hemoglobin which indicates that an increase in 2,3-bisphosphoglycerate causes a decrease in the affinity of oxygen to hemoglobin.
hemoglobin is a _____ while myoglobin is a ______
hemoglobin is a heterotetramer
myoglobin is a monomer
By itself heme (is/is not) a good oxygen carrier. It needs what
heme by itself is not a good oxygen carrier instead it needs to be part of a larger protein to prevent oxidation of the iron
Molecular oxgen binds _____ to Fe2+ in heme
reversibly
The heme prosthetic group is located ______ in the protein, with _____ groups exposed ______
The heme prosthetic group is located at the hydrophobic cleft in the protein, with propionate (propanoate) groups exposed at the surface.
Fe2+ is bound to hemoglobin when hemoglobin is in _____
R state
Oxygen is bounded to hemoglobin when hemoglobin is in _____
R state
Is the main conformation of deoxyhemoglobin R state or T state
T state
Is the main conformation of oxyhemoglobin R state or T state
R state
Oxygen binding stabilizes the _____
R state
As CO2 binds to hemoglobin, the affinity of hemoglobin for O2 ____
decreases
How does Fe3+ bind oxygen
It does not bind oxygen
When oxygen binds to the T state it causes a _____
causes a conformation change to the R state.
2,3- Bisophosphoglycerate binds between _____ in the _____ state and stabilizes the T state.
binds to the cavity between Beta units of hemoglobin in the T state and stabilizes the T state.
How is 2,3- Bisophosphoglycerate prevented from binding?
The conversion to the R state changes the shape and size of the cavity which prevents the binding of 2,3-bisphoglycerate.
_____ state has higher affinity for oxygen
R state
_____ state has lower affinity for oxygen
T state
which have shorter Fe-oxygen bond (R state or T state)
R state compared to T state
When heme groups binds oxygen the Fe-Nporphyrin bonds shorten doing what to the iron atom?
It moves the iron ion into the plane of the porphyrin ring.
Why can we say myoglobin has higher oxygen affinity based on a graph than hemoglobin?
myoglobin has hyperbolic curve while hemoglobin has a sigmoidal (S-shaped). therefore at all oxygen concentrations the myoglobin has a higher saturation than does hemoglobin thus myoglobin has the higher oxygen affinity.
In deoxyhemoglobin the sixth coordination site is ______ and the iron atom is ______
unoccupied (lacks oxygen) and the iron atom is out of the plane of the porphyrin ring.
When oxygen occupies the sixth coordination site, the iron atom ________
the iron atom moves into the plane as the conformation of the protein changes.
Why is hemoglobin more efficient at delivering oxygen then myoglobin?
Hemoglobin has a lower affinity for oxygen than myoglobin
Hemoglobins _____ affinity for oxygen allows it to release _____ in _____ concentration
low affinity for oxygen allows it to release oxygen in low oxygen concentrations.
when is oxygen released from myoglobin?
when the oxygen concentration falls to very low levels in the muscle tissues (skeletal and cardiac)
In the hill plot what is YO2 equal to?
number of occupied oxygen binding sites / the total number of binding sites on the protein.
The hill plot for myoglobin is ____ while the plot for hemoglobin is ____
hill plot for myoglobin is linear while the plot for hemoglobin is not linear.
The theoretical maximum value of n for hemoglobin is _____ but is this value ever reached?
max n value is 4 which would indicate complete cooperation between all subunits meaning all oxygen molecules would bind simultaneously. However the observed value is always less than 4 (the limit is never actually reached)
R and T state differ in ____
quaternary structure; they differ in a shift of the subunit positions relative to each other.
What will cause a hemoglobin curve shift to the right?
decreasing oxygen affinity and/or increases T state
In hemoglobin as oxygen pressure ____ and oxygen binds it causes ____ exposing _____ which account for ____
as oxygen pressure increases and oxygen binds it causes a conformation shift exposing more R state binding sites which accounts for the “S shape” nature of the curve.
The Bohr effect states that hemoglobin binding affinity is and pH is _____ to CO2
inversely proportional
As there is a ____ in acidity causes a increase in protons in the blood that ____
increase in acidity ( decrease in pH) causes an increase in protons in the blood that compete with oxygen in binding.
heme is a planar group with both ___ and ____ functions
polar and non polar functions
The polar propionate groups of heme are ___
at the surface of the protein
The nonpolar groups of the heme are _____
buried
Both myoglobin and hemoglobin require ____ to bind and carry oxygen
heme
What would happen if heme was not part of a protein?
The O2 binded to heme would oxidize Fe2+ to Fe3+ (which cannot bind oxygen), through a heme- O2-heme- intermediate. This intermediate is sterically hindered by the interaction between the protein and the oxygen-carrying heme group.
Hemoglobin is a heterotetramer with ___ chains and ___chains
2 alpha chains
and 2 beta chains each subunits contains a heme group.
Myoglobin is a monomer with ____ chain
one polypeptide with one heme
Normal hemoglobin is designate ____ while sickle cell hemoglobin is designated ____
normal hemoglobin (HbA) and sickle cell hemoglobin (HbS)
The mutated form of hemoglobin in sickle-cell anemia results from the replacement of ____ by a _____ at position ____ in the ____ of a protein
the replacement of the charged amino acid glutamate with the nonpolar residue valine at position 6 in the Beta chain of the protein
under conditions of low oxygen HbS does what?
aggregates and distorts the RBC into a sickle shape.
Sickled RBC are relatively _____ (flecible/inflexible) and may do what to the capillary beds causing ____.
relatively unstable and may clog the capillary beds causing pain and tissue damage.
How does sickled RBC lead to anemia
they have a shorter life span.
what is the residue that replaces glutamate to produce HbS
valine
What other residues can replace glutamate to produce a similar sickle cell effect
a non polar (hydrophobic) residue such a leucine residue, a isoleucine residue or an alanine
Why does sickling occur in deoxyhemoglobin but not in oxyhemoglobin?
Oxyhemoglobin has a small hydrophobic “pocket” in a Beta chain region located in the interior of the protein while deoxyhemoglobin has this hydrophobic pocket located on the surface of the protein. .
Why does sickle cell occur in deoxyhemoglobin
the val interacts with the hydrophobic pocket on the surface of another HbS molecule leading to aggregation of Hbs.
What are possible amino acids that reasonable candidates for pocket-Val 6 interactions? why?
This process is driven by hydrophobic interactions thus any hydrophobic amino acid is a resonable candidate.
(specific example include: leucine and phenylalanine)
Val 6-pocket interactions result in what?
a string of HbS molecules that eventually form an insoluble fiber and distort the shape of the RBC into a sickle shape.
The formation of aggregate sin HbS occurs when _____
[O2] falls and the deoxygenated T state begins to accumulate.
Anemia is a possible symptoms in people with variants with _____ hemoglobin because ____
Anemia is a possible symptom in people with unstable hemoglobin because the RBC containing degraded hemoglobin are more likely to be destroyed.
A person with a high-affinity variant may have ____ levels of RBC called ____
elevated levels of RBC called erthytocytosis or polycythemia.
Cyanosis is a possible symptom of what?
The stabilization of the T state or destabilization of the R state causing hemoglobin to have a decreased affinity for oxygen.
Hemoglobin kansas exhibits ____ cooperativity.
low
Allosteric enzymes have a ____ shaped curve
S shaped of V0 vs. [S]
Allosteric enzymes may have binding sites for _____ that are ____ from active sites
binding sites for regulatory molecules (heterotropic effectors) that are separate from enzyme’s active sites.
Allosteric enzymes undergo _____ as a result of modulator binding.
conformation changes.
If the substrate of allosteric enzymes is a substrate the effect is called a _____
homotropic effect.
Allosteric enzymes have multisubunit proteins that undergo conformational shifts between a more active site and a less active site as a result of ______.Do nonallosteric enzymes show the same conformation changes ?
Result of modulator binding
NO nonallosteric enzymes do not show these conformation changes
Why do allosteric enzymes have a S shape?
It is due to there cooperative interactions between subunits that alter the affinity of each subuit for substrate.
What type of enzymes have a hyperbolic curve?
Michaelis-Menten enzymes.
A negative modifier would do what to the graph of an allosteric enzyme?
Shift it to the left meaning that at a given substrate concentration there is a decrease in reaction velocity.
What does a positive modifier do to allosteric enzymes?
It binds to a regulatory site on the enzyme, stabilizing the R conformation and increasing the concentration of R.
How does a positive modifier shift the graph of allosteric enzymes?
Shifts it to the left thus at a given substrate concentration the reaction velocity increases; less substrate is needed to produce an equivalent amount of product.
If substrate concentration is decreased then what will happen to [T]/[R] why?
[T]/[R} would increase if substrate concentration decreases; less substrate is bound so less R state enzyme is stabilized
If a substrate concentration is increased what happens to [T]/[R]
[T]/[R] will decrease if substrate concentration increases; ration of [T] to [R] decreases because in positive cooperation, the binding of substrate to R state stabilizes it and enhances binding to other substrate molecules.
What happens to hemoglobin when it binds O2 at physiological pH’s?
It undergoes a conformation change that makes it a slightly stronger acid. It therefore releases protons on the binding oxygen. increasing pH, that is removing protons simulates Hb to bind O2.
~ ____ molecules of CO2 are formed per molecule of
0.8 molecules of CO2
The CO2 formed per molecule of O2 is consumed by ____ from the ____ to the ____ largely as dissolved CO2 forming _______.
The CO2 formed per molecule is consumed by respiration diffuse from the tissues to the capillaries largely as dissolved CO2 forming bicarbonate.
What is the reaction for bicarbonate in the body
CO2 + H2O —–> H+ + HCO3-
catalyzed in the erythrocytes by carbonic anhydrase.
Most of the CO2 in the blood is carried in the form of _____
bicarbonate.
In the capillaries where pO2 is ____ the H+ generated by _____ is taken up by Hb which is thereby induced to ______. This H+ uptake moreover facilitates ____ by stimulating ______.
In the capillaries where pO2 is low the H+ generated by bicrabonate formation is taken up by Hb where which is thereby induced to unload its bounded O2. This H+ uptake moreover facilitates CO2 transport by stimulating bicarbonate formation.
In the lungs where pO2 is ____, O2 binding by Hb releases _____, which ______CO2.
In the lungs where pO2 is high, O2 binding by Hb releases the Bohr protons, which drive off the CO2.
The reaction between the capillaries and the lungs are closely matched causing ______
little change in blood pH.
Why is the mechanism of Bohr effect important to highly active muscles?
It supplies additional O2; Highly active muscles generate acid so fast that they lower the pH of the blood passing through them from 7.4 to 7.2. At this lowered pH Hb releases ~10% more O2 at the <20 torr pO2 in these muscles then it does at a pH of 7.4
