Molec Biochem Ch 7

Which gas does not bind to the porphyrin ring Fe2+ ion in myoglobin? H2S NO CO CO2 O2

CO2

Carbon monoxide binds to Heme: -resulting in the oxidation of the Fe(II) to Fe(III). -in a manner that displaces carbon dioxide, causing CO2 poisoning. -from the side opposite oxygen, -resulting in a brown colored heme. -with a higher affinity than oxygen. -with a lower affinity than oxygen.

with a higher affinity than oxygen.

The Hill plot shows that the fourth oxygen binds to hemoglobin with ______-fold greater affinity than the first. 5 100 10 2 20

100

Which of the following is a role of histidine in myoglobin? -A histidine residue occupies the 6th coordination position of Fe2+. -A histidine residue forms a hydrogen bond with oxygen. -Histidine residues become protonated as part of the Bohr effect. -Protonated histidine residues aid in -BPG binding. -All of the above.

A histidine residue forms a hydrogen bond with oxygen.

Which of the following statements about 2,3-bisphosphoglycerate (BPG) binding is FALSE? -BPG binds less tightly to fetal hemoglobin than to adult hemoglobin, thereby aiding oxygen transfer to a fetus. -BPG requires a binding site containing multiple positively charged groups. -BPG binds to hemoglobin at one site and lowers hemoglobin's affinity for oxygen at another site. -BPG aids oxygen delivery to tissues by increasing the affinity of myoglobin for oxygen.

BPG aids oxygen delivery to tissues by increasing the affinity of myoglobin for oxygen.

Which of the following statements is FALSE with respect to hemoglobin's transition from the T state to the R state? -Contacts between side chains in the different subunits of hemoglobin change upon binding of oxygen to one subunit. -Helix F changes its secondary structure in response to oxygen binding. -The Fe2+ ion is pulled into the plane of the heme prosthetic group when oxygen binds to hemoglobin in the T state. -BPG is not required to stabilize the R state.

Helix F changes its secondary structure in response to oxygen binding.

Which term best describes the histidine F8 residue in myoglobin and hemoglobin? -Conservatively substituted residue. -Homologous residue. -Catalytic residue. -Variable residue. -Invariant residue

Invariant residue

If a Lys residue that interacts with 2,3-bisphosphoglycerate (BPG) in the central cavity of hemoglobin is changed to a Ser residue, how would this affect hemoglobin behaviour? -Oxygen binding would be less sensitive to pH. -Oxygen binding would be more sensitive to pH. -The T state would be less stable. -The T state would be more stable. -Both A and C would occur.

The T state would be less stable.

Which of the following statements about 2,3 bisphosphoglycerate (BPG) is TRUE? -BPG lowers myoglobin's affinity for oxygen. -BPG binds more tightly to fetal hemoglobin than to adult hemoglobin. -BPG binds at a site which contains multiple negatively-charged groups. -The affinity of BPG binding to Hb would be reduced if the N-terminal groups of the four subunits were modified to make them uncharged.

The affinity of BPG binding to Hb would be reduced if the N-terminal groups of the four subunits were modified to make them uncharged.

What happens when hemoglobin is converted from the deoxy (T) form to the oxy (R) form? -The heme becomes slightly dome-shaped and the iron lies out of the plane of the heme. -The central cavity becomes smaller. -The iron in heme is oxidized from Fe2+ to Fe3+. -Both A and B happen. -Both B and C happen.

The central cavity becomes smaller.

A newly-identified protein has a sigmoidal curve in a graph of fractional saturation versus ligand concentration. What can be deduced about this protein? -The protein has a constant high affinity for the ligand. -The protein has primary, secondary and tertiary structure, but not quaternary -The dissociation constant (Kd) of the ligand is low. -The protein binds the ligand cooperatively.

The protein binds the ligand cooperatively

Hemoglobin's p50 value is about ______ as great as myoglobin's p50 value. twice one-tenth half ten times twenty times

ten times

The value of n in the Hill equation for hemoglobin is about ______ as great as the value for myoglobin. three times half ten times twice five times

three times

Myoglobin's secondary structure is primarily composed of ______________. -alpha-helices -parallel beta-sheets -antiparallel beta-sheets -alpha-bends -beta-helices

-alpha-helices

What is the fractional saturation of myoglobin at pO2 = 2.8 torr, if p50 = 2.8 torr? 0.50 0.28 1.00 2.80

0.50

What is the fractional saturation of myoglobin at pO2 = 7.2 torr, if P50 = 2.8 torr? 1.00 0.50 0.72 0.28

0.72

______ of the world's human population carry a variant hemoglobin. 75% 90% 25% 5% 50%

5%

What type of allosteric effector is BPG? -A homoallosteric effector of myoglobin. -A homoallosteric effector of hemoglobin. -A heteroallosteric effector of myoglobin. -A heteroallosteric effector of hemoglobin. -Both C and D are correct

A heteroallosteric effector of hemoglobin

The binding of one O2 to a molecule of hemoglobin results in: -A decrease in hemoglobin's ability to bind a second O2. -An increased affinity for O2 in the remaining subunits (which have not yet bound O2). -Dissociation of the hemoglobin subunits. -The release of any other O2 that may have bound earlier. -The movement of hemoglobin to an organism's muscle tissue

An increased affinity for O2 in the remaining subunits (which have not yet bound O2).

Why is BPG essential for the delivery of O2 to the tissues? -BPG stabilizes the R state conformation of hemoglobin. -BPG stabilizes O2 binding to hemoglobin. -BPG stabilizes the association of hemoglobin subunits. -BPG stabilizes the T state conformation of hemoglobin.

BPG stabilizes the T state conformation of hemoglobin.

Which of the following statements about factors relating to the Bohr effect and the effect on CO2 on oxygen transport is NOT true: -CO2 modulates O2 binding to hemoglobin by combining reversibly with the N-terminal groups of other blood proteins to form carbonates. The protons released in this reaction promote further O2 release through the Bohr effect. -CO2 also modulates O2 binding to hemoglobin by allosterically binding the T state but not the R state: Thus when the CO2 concentration is high, as it is in the capillaries, it stabilizes T state, stimulating hemoglobin to release its bound O2. -Under physiological conditions, hemoglobin releases ~ 0.6 protons for each bound O2. -The reason for the Bohr effect on the molecular level is because in hemoglobin's T-state, the formation of ion pairs increases the pK values of certain groups whereas these ion pairings are absent in its R-state and the pK's of the groups decrease (making them more acidic and more likely to give up protons). -Dissolved CO2 is converted to bicarbonate by the enzyme carbonic anhydrase. A proton (H+) is released in the reaction: Thus, the release of CO2 by actively respiring cells causes the release of protons causing hemoglobin to release the oxygen needed by these cells via the Bohr effect. -The Bohr effect involves the O2 affinity of hemoglobin increasing with increasing pH. Thus increasing the pH stimulates hemoglobin to bind more oxygen.

CO2 modulates O2 binding to hemoglobin by combining reversibly with the N-terminal groups of other blood proteins to form carbonates. The protons released in this reaction promote further O2 release through the Bohr effect.

Why is the decreased affinity of fetal hemoglobin for BPG advantageous? -With fewer BPG molecules bound there are more heme residues available for O2 binding. -Decreased BPG binding biases the fetal hemoglobin toward the R state. -More free BPG is available to bind to adult hemoglobin, resulting in a shift to the R state. -BPG is available to bind to fetal myoglobin, helping to release O2 in fetal muscle tissue. -None of the above.

Decreased BPG binding biases the fetal hemoglobin toward the R state.

Which of the following statments about Sickle Cell anemia is INCORRECT? -Individuals who are heterozygous carriers of hemoglobin S in an area where malaria is prevalent are more likely to survive to maturity than individuals who are homozygous for normal hemoglobin. -Hemoglobin S has a lower affinity for oxygen than normal adult hemoglobin (hemoglobin A). -The mutation causing sickle cell anemia is that hemoglobin S contains Val rather than Glu at the sixth position of each beta chain. -Sickle-cell anemia is caused from deoxyhemoglobin S forming insoluble filaments. -The administration of hydroxyurea is an effective treatment for sickle-cell anemia.

Hemoglobin S has a lower affinity for oxygen than normal adult hemoglobin (hemoglobin A).

Which of the statements below about hemoglobin and myoglobin's oxygen binding is INCORRECT: -Myoglobin has a higher affinity for oxygen than hemoglobin. -The Hill coefficient (n) increases with the degree of cooperativity of a reaction: A Hill coefficient of 1 (n = 1) indicates no cooperativity, a Hill coefficient < 1 (n < 1) indicates negative cooperativity and a Hill coefficient > 1 (n > 1) indicates positive cooperativity. -In any binding system, a sigmoidal curve is diagnostic of a cooperative interaction between binding sites whereas a hyperbolic binding curve is an indication of a lack of cooperativity. -Hemoglobin has a Hill coefficient > 1 whereas myoglobin has a Hill coefficient < 1. -The reason hemoglobin has a sigmoidal or S-shaped oxygen binding curve whereas myoglobin has a hyperbolic oxygen binding curve is because hemoglobin is a tetramer whereas myoglobin is a monomer. -The p50 of hemoglobin is nearly 10 times higher than that of myoglobin.

Hemoglobin has a Hill coefficient > 1 whereas myoglobin has a Hill coefficient < 1.

During the T to R conformational shift, Fe(II) drags the F-helix via a bond to the side chain of ________. His F8 Leu FG3 Val FG5 Leu F7 Leu F4

His F8

Why is hemoglobin's affinity for oxygen sensitive to small changes in pH (the Bohr effect)? -Histidine side chains in the central cavity of hemoglobin are charged at lower pH, decreasing BPG binding. -The affinity of the proximal histidine for the heme Fe2+ ion is pH-dependent. -The distal histidine becomes charged at lower pH, forcing the oxygen out of its binding pocket. -Histidine side chains in hemoglobin become charged at lower pH forming salt bridges that stabilize the T state.

Histidine side chains in hemoglobin become charged at lower pH forming salt bridges that stabilize the T state.

Which of the following statements does not apply to the K value in the equation for the oxygen binding curve of myoglobin? -It is defined as that oxygen partial pressure at which half of the oxygen binding sites are occupied. -It is the value of pO2 at which Y = 0.5. -It is a measure of the affinity of myoglobin for oxygen. -If Y > K, then myoglobin is less than 50% saturated with oxygen. -It is numerically equal to p50.

If Y > K, then myoglobin is less than 50% saturated with oxygen.

If hemoglobin is in the T state, what happens at one -subunit when the other -subunit binds oxygen? -It maintains the T state until its β-subunit binds oxygen. -Its N-terminal becomes protonated. -Its F-helix moves. -It decreases its affinity for oxygen.

Its F-helix moves

Protein X binds reversibly to ligand Y such that X + YXY, and the molar concentrations of X, Y and XY are known. Which of the following represents the dissociation constant (Kd) for this reaction? -Kd = [X][Y]/[XY] -Kd could not be determined with the information provided. -Kd = [XY]/[X][Y] -Kd = [X] + [Y]/[X + Y] -Kd = [XY]/[Y]

Kd = [X][Y]/[XY]

Which of the following statements about diseases of hemoglobin and the blood is not true: -Mutations to that destabilize hemoglobin's tertiary or quaternary structure, alter its oxygen-binding affinity (p50) and reduce its cooperativity result in diseased states. -The bluish skin color associated with cyanosis is due to the presence of methemoglobin in the arterial blood. -Cyanosis is caused by mutations that favor the oxidation of Fe(II) to Fe(III). -Most mutations to hemoglobin observed in nature (i.e. hemoglobin variants) result in a lethal condition. -Mutations that increase hemoglobin's oxygen affinity lead to increased numbers of erythrocytes in order to compensate for the less than normal amount of oxygen released in the tissues - a condition named polycythemia. -Hemolytic anemia results from the lysis of erythrocytes. -Most of the variant hemoglobins identified result from a single amino acid substitution in a globin polypeptide chain.

Most mutations to hemoglobin observed in nature (i.e. hemoglobin variants) result in a lethal condition.

Structurally, myoglobin and hemoglobin are very similar proteins. In which of the following levels of structure do they differ most? Tertiary structure. Quaternary structure. Primary structure. Secondary structure.

Quaternary structure

Which of the statements below about hemoglobin is INCORRECT: -Hemoglobin is a tetramer made up of myoglobin-like subunits. -It has been dubbed an "honorary enzyme" even though it functions in oxygen transport and does not catalyze a chemical reaction. -The quaternary structure of hemoglobin consists of 4 polypeptide chains. -Hemoglobin gives red blood cells their color. -Hemoglobin is part of an oxygen delivery system that is needed for animals that are too large for oxygen to be delivered by simple diffusion. -Subunit interfaces in hemoglobin are composed of predominantly salt bridges.

Subunit interfaces in hemoglobin are composed of predominantly salt bridges.

Which of the following statements about the T and R states of hemoglobin is FALSE? -In the R state, the Fe2+ ion lies in the plane of the heme. -The R state has a smaller central cavity than the T state. -The T state has a lower affinity for oxygen than the R state. -The T state is less stable than the R state at lower pH.

The T state is less stable than the R state at lower pH.

Which of the following statements about hemoglobin is TRUE? -In the Bohr effect the binding of oxygen to hemoglobin is increased by the presence of H+ ions and CO2. -Hemoglobin differs from myoglobin because it contains more β-pleated sheet structure. -The affinity of fetal hemoglobin for -oxygen is higher than that of maternal hemoglobin. -Variations in the primary structure of hemoglobin always result in genetic diseases.

The affinity of fetal hemoglobin for -oxygen is higher than that of maternal hemoglobin

One of the adaptations to high altitude is an increase in the concentration of BPG in red blood cells. What effect does this have on the oxygen binding curve of hemoglobin and why? -The curve is shifted to the left because hemoglobin binds oxygen more tightly. -The curve is shifted to the left because hemoglobin has a lower Kd (dissociation constant). -The curve is shifted to the right, because hemoglobin has a lower affinity for oxygen. -The curve is shifted to the right, because hemoglobin has tighter oxygen binding.

The curve is shifted to the right, because hemoglobin has a lower affinity for oxygen.

Which of the following is NOT a role of histidine in hemoglobin? -The distal histidine occupies the 6th coordination position of Fe2+. -Histidine residues become protonated as part of the Bohr effect. -The proximal histidine occupies the 5th coordination position of Fe2+. -Protonated histidine residues aid in BPG binding

The distal histidine occupies the 6th coordination position of Fe2+

Which of the following statements correctly describes the interaction between an allosteric protein and an allosteric effector? -The effector binds reversibly at a specific site on one subunit of the protein, causing a global change in conformation. -The effector binds covalently at a specific site on the protein, causing a global change in shape. -The effector activates the protein by causing it to switch from its T (low affinity) to R (high affinity) form. -The effector binds non-specifically to one subunit and through induced fit initiates cooperativity between the subunits.

The effector binds reversibly at a specific site on one subunit of the protein, causing a global change in conformation.

Which of the statements below about hemoglobin's oxygen binding is INCORRECT: -In any binding system, a sigmoidal ligand binding curve (like hemoglobin's for O2) indicates an allosteric effect where there is cooperative interaction between binding sites and generally indicates that a protein has more than one subunit. -The binding of oxygen to hemoglobin in an example of positive cooperativity: Oxygen binding favors the T --> R transition switching hemoglobin from the low affinity for oxygen T-state to the high affinity for oxygen R-state. -Oxygen binding causes a change in the quaternary structure of hemoglobin where hemoglobin changes quaternary structure from the T (tense) state that has a low affinity of oxygen to the R (relaxed) state that has a higher affinity of oxygen. -The T --> R transition in hemoglobin subunits explains the difference in the oxygen affinities of oxy- and deoxyhemoglobin. -Hemoglobin's sigmoidal oxygen binding curve is due to the T --> R transition: The sigmoidal curve results because of the switch from a low affinity oxygen binding hyperbolic curve in the T-state to a high affinity oxygen binding hyperbolic curve in the R-state. -The cooperative binding of O2 by hemoglobin is an example of an allosteric effect (Greek: allos, other stereos, solid or space). Allosteric effects, in which the binding of a ligand at one site affects the binding of another ligand at another site, generally require interactions among subunits of oligomeric proteins. -The hemoglobin tetramer can bind 4 molecules of oxygen and because of its positive cooperativity, the fourth O2 molecule binds with 4-fold greater affinity than the first.

The hemoglobin tetramer can bind 4 molecules of oxygen and because of its positive cooperativity, the fourth O2 molecule binds with 4-fold greater affinity than the first.

Consider a hypothetical hemoglobin with a Hill coefficient of 1 and the same p50 value as normal hemoglobin. Choose the statement below that best describes the two proteins. -The two hemoglobins would be able to deliver about the same amount of oxygen to the tissues. -The hypothetical hemoglobin has a greater oxygen affinity than normal hemoglobin. -There is a cooperative interaction between oxygen-binding sites in both the hypothetical and normal hemoglobins. -The oxygen binding curve for the hypothetical hemoglobin is hyperbolic, and the curve for normal hemoglobin is sigmoidal. -At pO2 less than p50, normal hemoglobin has a greater YO2 value.

The oxygen binding curve for the hypothetical hemoglobin is hyperbolic, and the curve for normal hemoglobin is sigmoidal.

If the gene for myoglobin is knocked out in mice, the mice: -respire extremely rapidly. -have larger lungs. -appear normal, with lighter colored muscle tissue. -have their growth stunted. -have dark brown muscle tissue

appear normal, with lighter colored muscle tissue.

BPG stands for: bisphenylglycerol betapropylglutamine boronylphenylglutamate bisphosphoglycerate biphenylglycine

bisphosphoglycerate

The most rapid way that erythrocytes adapt to high altitudes is: -by producing genetically altered hemoglobins that have higher O2--binding affinities. -by increasing the intracellular concentration of BPG. -by adopting the symmetry model of allosterism. -by increasing the concentration of hemoglobin. -by relying upon the simpler protein myoglobin.

by increasing the intracellular concentration of BPG.

Myoglobin's primary physiological role is to facilitate oxygen ________. binding storage reduction diffusion metabolism

diffusion

Within the sequence of steps in the Perutz mechanism explaining Hb's cooperative binding of O2, listed following in no particular order, select the position in the order in which the step "Residues at the alpha-beta interfaces move, and ion pairs involving the C-terminal residues are broken" occurs: - His F8 is pulled towards the heme. - Residues at the - interfaces move, and ion pairs involving the C-terminal residues are broken. - Oxygen binds to deoxyhemoglobin. - Helix F tilts and is translated by about 1 Angstrom. - Fe(II) is pulled into the plane of the porphyrin. fifth third fourth first second

fifth

Within the sequence of steps in the Perutz mechanism explaining Hb's cooperative binding of O2, listed following in no particular order, select the position in the order in which the step "Oxygen binds to deoxyhemoglobin" occurs: - His F8 is pulled towards the heme. - Residues at the - interfaces move, and ion pairs involving the C-terminal residues are broken. - Oxygen binds to deoxyhemoglobin. - Helix F tilts and is translated by about 1 Angstrom. - Fe(II) is pulled into the plane of the porphyrin. fifth fourth third first second

first

Within the sequence of steps in the Perutz mechanism explaining Hb's cooperative binding of O2, listed following in no particular order, select the position in the order in which the step "Helix F tilts and is translated by about 1 Angstrom" occurs: - His F8 is pulled towards the heme. - Residues at the - interfaces move, and ion pairs involving the C-terminal residues are broken. - Oxygen binds to deoxyhemoglobin. - Helix F tilts and is translated by about 1 Angstrom. - Fe(II) is pulled into the plane of the porphyrin. fifth fourth second first third

fourth

Which of the following amino acids has the most significant role in the molecular mechanisms of hemoglobin's function? histidine lysine glycine glutamate tyrosine

histidine

While the binding of O2 to myoglobin as a function of pO2 is described by a simple __________ curve, thebinding to hemoglobin is described by a more complex ______ curve. -exponential; hyperbolic -hyperbolic; sigmoidal -sigmoidal; bell-shaped -hyperbolic; concave -sigmoidal; hyperbolic

hyperbolic; sigmoidal

The rearrangement of T-form hemoglobin to the R-form: -increases the ion pairing interactions of the C-terminal amino acids. -opens a central cavity for BPG binding. -occurs in each protein subunit independently when its heme binds oxygen. -requires the binding of at least three oxygen molecules. -involves the movement of the Fe(II) into the heme plane.

involves the movement of the Fe(II) into the heme plane.

Some abnormal hemoglobins have Hill coefficients that are ______ that of normal hemoglobin, indicating that their ability to bind oxygen cooperatively has been compromised. -about equal to -much greater than -cannot be determined from the information given -less than -greater than

less than

Hemoglobin S, the variant responsible for the misshapen red blood cells characteristic of the disease sickle-cell anemia, is potentially advantageous to heterozygotes because it confers some level of resistance to the disease _________. cyanosis AIDS polycythemia malaria rickets

malaria

Noncooperative binding is characterized by a Hill coefficient of what value? 0 < n < 1 n > 1 n = 0 n = 1

n = 1

Hemerythrin and hemocyanin are: -synthetic derivatives of hemoglobin's heme group used in artificial blood substitutes. -oxygen transport proteins found in invertebrates. -hemoglobin variants that are found in animals at high altitude. -tetrameric hemoglobin derivatives containing only -chains (4 tetramers). -human mutant hemoglobins with decreased oxygen affinity.

oxygen transport proteins found in invertebrates

Within the sequence of steps in the Perutz mechanism explaining Hb's cooperative binding of O2, listed following in no particular order, select the position in the order in which the step "Fe(II) is pulled into the plane of the porphyrin" occurs: - His F8 is pulled towards the heme. - Residues at the - interfaces move, and ion pairs involving the C-terminal residues are broken. - Oxygen binds to deoxyhemoglobin. - Helix F tilts and is translated by about 1 Angstrom. - Fe(II) is pulled into the plane of the porphyrin. fifth first second third fourth

second

Myoglobin and a single chain of hemoglobin have similar ______ structures. primary secondary tertiary quaternary none of the above

tertiary

If the binding of O2 to hemoglobin was characterized by a Hill constant of -1: -the sequential model of allosterism would be eliminated as a reasonable model. -the binding of the first O2 would increase the affinity of the hemoglobin for O2. -hemoglobin would not be able to release bound O2. -the O2 binding curve would be hyperbolic. -the binding of the first O2 would decrease the affinity of the hemoglobin for O2.

the binding of the first O2 would decrease the affinity of the hemoglobin for O2.

The reaction of carbonic anhydrase catalyzes: -the hydration of bicarbonate, resulting in the formation of carbonic acid -the hydrolysis of carbamates with the concomitant consumption of protons -the hydration of carbon dioxide, forming bicarbonate and protons -the formation of carbamates with the concomitant release of protons -the reduction of carbon dioxide with the concomitant consumption of protons

the hydration of carbon dioxide, forming bicarbonate and protons

Within the sequence of steps in the Perutz mechanism explaining Hb's cooperative binding of O2, listed following in no particular order, select the position in the order in which the step "His F8 is pulled towards the heme" occurs: - His F8 is pulled towards the heme. - Residues at the - interfaces move, and ion pairs involving the C-terminal residues are broken. - Oxygen binds to deoxyhemoglobin. - Helix F tilts and is translated by about 1 Angstrom. - Fe(II) is pulled into the plane of the porphyrin. third first fourth fifth second

third

In sickle-cell anemia, the negatively charged glutamic acid residue is replaced by the neutral amino acid ____________. glycine tyrosine valine adenosine lysine

valine