Biochemistry I Chapter 7 Problems

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

*0.50 **Y = pO2 / (p50 + pO2) = 2.8 / (2.8 + 2.8) = 0.5

Which of the curves does NOT show cooperative binding? 1 2 3 4 None of the above

*1 *Curve 1 is hyperbolic, which is typically seen with non-cooperative binding.

Which of the curves in the graph represents the binding of oxygen to a monomeric oxygen binding protein? 1 2 3 4 None of the above

*1 *Monomeric oxygen binding proteins such as myoglobin and the individual globin subunits of hemoglobin, bind oxygen with high-affinity and have a hyperbolic binding curve. The cooperative binding behaviour represented by a sigmoidal binding curve typically requires multiple subunits.

Which of the curves in the graph represents the binding of oxygen to myoglobin? 1 2 3 4 None of the above

*1 *Myogobin binds oxygen with high-affinity, which is represented by a hyperbolic binding curve.

If curve 3 represents the binding of oxygen to normal hemoglobin, which curve would represent the binding behaviour of a single α-globin subunit? 1 2 3 4 None of the above

*1 *When dissociated from one another, the subunits of hemoglobin cannot adopt a low-affinity conformation and so they behave like myoglobin, binding oxygen with a fixed high-affinity which gives a hyperbolic binding curve.

If curve 3 represents the binding of oxygen to normal Hb, which curve represents the binding of oxygen to Hb that has dissociated into separate subunits? 1 2 3 4 None of the above

*1 *When dissociated from one another, the subunits of hemoglobin cannot adopt a low-affinity conformation and so they behave like myoglobin, binding oxygen with a fixed high-affinity.

If curve 3 represents the binding of oxygen to Hb at pH 7.2, which curve represents the binding of oxygen to Hb at pH 7.6? 1 2 3 4 None of the above

*2

If curve 3 represents the binding of oxygen to Hb in normal red blood cells, which of the curves would represent the binding of oxygen to Hb in red blood cells that contain NO BPG? 1 2 3 4 None of the above

*2

The graph shows several oxygen binding curves obtained for hemoglobin (Hb) under different experimental conditions. If curve 3 represents the oxygen binding behaviour of normal adult Hb, which curve represents the oxygen binding behaviour of fetal Hb? 1 2 3 4 None of the above

*2

If curve 3 represents the binding of oxygen to normal hemoglobin, which curve represents the binding of oxygen to hemoglobin when a His that interacts with BPG is mutated to a Gly? 1 2 3 4 None of the above

*2 *Because one of the positively-charged residues involved in BPG binding has been substituted, it is likely that the mutated hemoglobin binds BPG with lower affinity. This means that the R state of hemoglobin is favoured relative to the T state, and so the oxygen-binding curve will shift to the left.

If curve 3 represents oxygen binding to Hb in normal red blood cells, which curve represents oxygen binding to Hb in red blood cells that contain a greater concentration of BPG? 1 2 3 4 None of the above

*4

If curve 3 represents the binding of oxygen to Hb at pH 7.4, which curve represents the binding of oxygen to Hb at pH 7.2? 1 2 3 4 None of the above

*4 *A change from pH 7.4 to pH 7.2 represents an increase in the concentration of H+ ions. As the concentration of H+ ions increases, BPG binds to hemoglobin with greater affinity. The T state of hemoglobin is thus favoured and its fraction saturation decreases, especially at lower concentrations of oxygen. The binding curve will shift to the right relative to its position at pH 7.4.

If curve 3 represents the binding of oxygen to Hb in normal red blood cells, which of the curves would represent the binding of oxygen to Hb in red blood cells that contain an increased concentration of BPG as a consequence of adaptation to high altitudes? 1 2 3 4 None of the above

*4 *An increased concentration of BPG in red blood cells results in an increased binding of BPG to hemoglobin. The T state of hemoglobin is thus favoured and its fraction saturation decreases, especially at lower concentrations of oxygen. The binding curve would thus shift to the right relative to curve 3.

Which of the following statements about the structure of myoglobin is TRUE? The heme group is loosely associated with myoglobin via hydrophobic interactions. A heme prosthetic group is tightly bound to myoglobin via a coordination bond. Myoglobin contains a heme prosthetic group that is slotted into a hydrophilic pocket between α-helix E and α-helix F. The heme prosthetic group is an integral part of the protein's secondary structure.

*A heme prosthetic group is tightly bound to myoglobin via a coordination bond.

What type of allosteric effector is BPG? A heteroallosteric effector of myoglobin. A heteroallosteric effector of hemoglobin. A homoallosteric effector of myoglobin. A homoallosteric effector of hemoglobin.

*A heteroallosteric effector of hemoglobin. *BPG is a heteroallosteric effector because it alters the ability of hemoglobin to bind another ligand, oxygen.

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. *Oxygen binding to myoglobin involves the formation of a hydrogen bond between the oxygen molecule and the distal histidine.

What type of allosteric effector is oxygen? A heteroallosteric effector of myoglobin. A heteroallosteric effector of hemoglobin. A homoallosteric effector of hemoglobin. A homoallosteric effector of myoglobin.

*A homoallosteric effector of hemoglobin. *Oxygen causes hemoglobin to switch to the R state, which has a greater affinity for oxygen. This is a homoallosteric effect.

Which of the following statements is FALSE? In its interaction with hemoglobin, oxygen is: reversibly bound. a prosthetic group. homoallosteric effector. bound at the 6th coordination position of the Fe(II) ion in the heme. a ligand.

*A prosthetic group. *Oxygen is not a prosthetic group.

The binding of one O2 to a molecule of hemoglobin results in: The release of any other O2 that may have bound earlier. Dissociation of the hemoglobin subunits. A decrease in hemoglobin's ability to bind a second O2. 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).

*An increased affinity for O2 in the remaining subunits (which have not yet bound O2). *When hemoglobin is in the T state, binding of oxygen to one subunit triggers a global change in conformation. This increases the affinity of the remaining subunits for oxygen.

Which of the following statements about BPG and its effect on oxygen transport is NOT true: The effects of BPG also help supply the fetus with oxygen. A fetus obtains its O2 from the maternal circulation via the placenta. BPG binds more tightly to adult hemoglobin than to fetal hemoglobin thus facilitating the transfer of O2 to the fetus. The presence of BPG in mammalian erythrocytes decreases hemoglobin's affinity for oxygen. BPG stands for D-2,3 bisphosphoglycerate, shown below: An intial response in adapting to a higher altitude is increased BPG synthesis in erythrocytes. This increase in BPG causes the O2-binding curve of hemoglobin to shift from its sea-level position to a higher affinity position facilitating better O2 absorption and transport at the elavated altitude. BPG binds in hemoglobin's central cavity in the T state but not in the R state. Thus because it binds (and thus stablizes) the T state, BPG has a negative allosteric effect on hemoglobin's binding of oxygen.

*An intial response in adapting to a higher altitude is increased BPG synthesis in erythrocytes. This increase in BPG causes the O2-binding curve of hemoglobin to shift from its sea-level position to a higher affinity position facilitating better O2 absorption and transport at the elavated altitude. **BPG plays a role in high-altitude adaptation. An intial response to moving to a higher altitude is increased BPG synthesis in erythrocytes. This increase in BPG causes the O2-binding curve of hemoglobin to shift from its sea-level position to a lower affinity position - this is actually favorable because it has a steeper slope and delivers more oxygen between the reduced atmospheric pO2 of the elevated altitude and veinous pO2 (see Box 7-3 in the text).

Select the statement that best matches the following: Monoclonal antibodies Antibodies produced by hybridoma cells. Fragments of proteolyzed IgG that have antigen-binding sites. Diverse group of proteins also known as antibodies. Cells that mediate cellular immunity. Cells that mediate humoral immunity.

*Antibodies produced by hybridoma cells.

The enzyme 2,3-BPG mutase produces 1,3-BPG in red blood cells. Which of the following amino acids would you predict to find in the active site of 2,3-BPG mutase? Asp Glu Arg Leu Phe

*Arg *At physiological pH, Arg has a positively charged side chain. Given that both 2,3-BPG and 1,3-BPG are negatively charged, Arg might play a role in substrate binding in the active site.

________ diseases involve the loss of self-tolerance.

*Autoimmune

Shown below is a general diagram of the oxygen binding site as it occurs hemoglobin and myoglobin. Which item in the diagram is incorrectly labeled? A (Val E11) D (O2) B (His F8) C (Phe CD1)

*B

Which of the following statements about 2,3-bisphosphoglycerate (BPG) binding is FALSE? BPG requires a binding site containing multiple positively charged groups. BPG binds less tightly to fetal hemoglobin than to adult hemoglobin, thereby aiding oxygen transfer to a fetus. BPG aids oxygen delivery to tissues by increasing the affinity of myoglobin for oxygen. 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. *This statement is false. BPG does not affect the affinity of myoglobin for oxygen.

Why is BPG essential for the delivery of O2 to the tissues? BPG enables stabilization of the T state conformation. BPG enables hemoglobin to adopt the R state conformation.

*BPG enables stabilization of the T state conformation.

Why is BPG essential for the delivery of O2 to the tissues? BPG stabilizes the T state conformation of hemoglobin. 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. *The T state of hemoglobin has lower affinity for oxygen and this enables release of oxygen in the tissues.

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. 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. 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). 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. **CO2 modulates O2 binding to hemoglobin by combining reversibly with the N-terminal groups of other blood proteins to form carbamates.

Select the statement that best matches the following: Troponin C Major component of the thin filament of the myofibril. Functional unit of the myofibril. Calcium binding protein. Major component of the thick filament of the myofibril. Chemical energy source for muscle contraction.

*Calcium binding protein.

How is muscle contraction stimulated by calcium ions? Calcium ions are released from the sarcoplasmic reticulum and bind to actin, promoting its binding to myosin. Calcium ions are released from the sarcoplasmic reticulum and bind to troponin C, promoting the binding of myosin to actin. Calcium ions are released from the sarcoplasmic reticulum and bind to tropomyosin, stimulating its ATPase activity. Calcium ions are released from the sarcoplasmic reticulum and bind to myosin, stimulating ATPase activity.

*Calcium ions are released from the sarcoplasmic reticulum and bind to troponin C, promoting the binding of myosin to actin.

Select the statement that best matches the following: T lymphocytes, or T cells Diverse group of proteins also known as antibodies. Antibodies produced by hybridoma cells. Cells that mediate humoral immunity. Fragments of proteolyzed IgG that have antigen-binding sites. Cells that mediate cellular immunity.

*Cells that mediate cellular immunity.

Select the statement that best matches the following: B lymphocytes, or B cells Fragments of proteolyzed IgG that have antigen-binding sites. Cells that mediate cellular immunity. Cells that mediate humoral immunity. Diverse group of proteins also known as antibodies. Antibodies produced by hybridoma cells.

*Cells that mediate humoral immunity.

Select the statement the best matches that following: ATP Chemical energy source for muscle contraction. Calcium binding protein. Functional unit of the myofibril. Major component of the thick filament of the myofibril. Major component of the thin filament of the myofibril.

*Chemical energy source for muscle contraction.

Which of the following is not a rule of the symmetry model of allosterism? Conformational changes occur sequentially as more ligand-binding sites are occupied. The molecular symmetry of the protein is conserved during the conformational change. An allosteric protein is an oligomer of symmetrically related subunits. Each oligomer can exist in two conformational states, designated R and T; these states are in equilibrium.

*Conformational changes occur sequentially as more ligand-binding sites are occupied.

Select the statement that best matches the following: Immunoglobulins Fragments of proteolyzed IgG that have antigen-binding sites. Antibodies produced by hybridoma cells. Cells that mediate humoral immunity. Diverse group of proteins also known as antibodies. Cells that mediate cellular immunity.

*Diverse group of proteins also known as antibodies.

A secondary immune response is less intense than a primary response. True False

*False

Actin monomers spontaneously assemble into microfilaments. False True

*False

The R-state represents the conformation of deoxyhemoglobin and the T-state represents the conformation of oxyhemoglobin. False True

*False **The opposite is true.

Select the statement that best matches the following: Fab fragments Cells that mediate cellular immunity. Fragments of proteolyzed IgG that have antigen-binding sites. Cells that mediate humoral immunity. Antibodies produced by hybridoma cells. Diverse group of proteins also known as antibodies.

*Fragments of proteolyzed IgG that have antigen-binding sites.

Select the statement that best matches the following: Sarcomere Functional unit of the myofibril. Calcium binding protein. Major component of the thin filament of the myofibril. Major component of the thick filament of the myofibril. Chemical energy source for muscle contraction.

*Functional unit of the myofibril.

Which of the following statements is not true about IgG? The heavy chain of an IgG molecule is composed of four similar domains made of beta sheets. The antigen-binding site is located at the tip of each Fab fragment in a crevice between its VL and VH domains Has a Y-shaped general structure. Has two antigen binding sites that can recognize and bind different antigens. The antigen binding sites have an immunoglobulin fold motif (a sandwich composed of three- and four-stranded antiparallel sheets that are linked by a disulfide bond).

*Has two antigen binding sites that can recognize and bind different antigens.

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

*Helix F changes its secondary structure in response to oxygen binding. *This statement is false. While the relative position of Helix F does change in response to oxygen binding, the secondary structure of the helix is unaltered.

Which of the following statments about Sickle Cell anemia is INCORRECT? The mutation causing sickle cell anemia is that hemoglobin S contains Val rather than Glu at the sixth position of each beta chain. 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. Sickle-cell anemia is caused from deoxyhemoglobin S forming insoluble filaments. Hemoglobin S has a lower affinity for oxygen than normal adult hemoglobin (hemoglobin A). 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: The p50 of hemoglobin is nearly 10 times higher than that of myoglobin. 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. Hemoglobin has a Hill coefficient > 1 whereas myoglobin has a Hill coefficient < 1. 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.

Which of the following diseases is not caused by a mutation in hemoglobin? Hemophilia Hemolytic anemia Sickle-cell anemia Polycythemia

*Hemophilia

In myoglobin, the amino acid ________ F8 is the only ligand for the heme that is supplied by the protein.

*His

Hemoglobin's affinity for oxygen is sensitive to small changes in pH (the Bohr effect). Which of the following amino acid(s) is/are primarily responsible for this? Lysine residues in the protein's central cavity. The distal histidine. Histidine residues in the protein's central cavity.

*Histidine residues in the protein's central cavity.

Which of the following occurs in hemoglobin when blood pH is lowered? Histidine side chains at the subunit interface are charged at lower pH, forming salt bridges that stabilize the T state. The distal histidine becomes charged at lower pH, resulting in a lower affinity of the heme. The proximal histidine becomes charged at lower pH, which weakens the binding of heme in its pocket. Hemoglobin binds BPG with reduced affinity because histidine side chains in the central cavity of hemoglobin are charged at lower pH.

*Histidine side chains at the subunit interface are charged at lower pH, forming salt bridges that stabilize the T state.

Why is hemoglobin's affinity for oxygen sensitive to small changes in pH (the Bohr effect)? 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. The affinity of the proximal histidine for the heme Fe2+ ion is pH-dependent. Histidine side chains in the central cavity of hemoglobin are charged at lower pH, decreasing BPG binding.

*Histidine side chains in hemoglobin become charged at lower pH forming salt bridges that stabilize the T state. *Histidine side chains in hemoglobin are more likely to be charged at lower pH and some of these charged side chains can form salt bridges that help to stabilize the T state. (Other histidine side chains, located in the central cavity, increase the binding affinity for BPG at lower pH. Together, these two events confer hemoglobin's sensitivity to changes in pH.)

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

*Histidine. *Histidine residues play several critical roles in hemoglobin function. For example, think of the proximal histidine, the distal histidine, and the histidine residues involved in the binding of 2,3-bisphosphoglycerate (BPG).

Which of the following statements is (are) correct about curves 1-4 in the figure? Curve 1 represents O2 binding to myoglobin or to hemoglobin in the absence of BPG. If curve 3 describes O2 binding to hemoglobin at sea level, curve 2 describes O2 binding to hemoglobin at high altitude. If curve 3 describes O2 binding to hemoglobin at pH 7.6, curve 4 describes O2 binding to hemoglobin at pH 7.2.

*If curve 3 describes O2 binding to hemoglobin at sea level, curve 2 describes O2 binding to hemoglobin at high altitude. *If curve 3 describes O2 binding to hemoglobin at pH 7.6, curve 4 describes O2 binding to hemoglobin at pH 7.2.

Which of the following statements is FALSE? In fetal hemoglobin the central cavity is lined with more histidines than in adult hemoglobin, which results in preferential stabilization of the R-state. Actively respiring tissues have a relatively low pH and low pO2, which favors the T-state of hemoglobin. Fetal hemoglobin has a weaker affinity for BPG than maternal hemoglobin, resulting in a shift of the oxygen-binding curve to the left. As pH decreases, the O2 binding curve of hemoglobin shifts to the right, because a greater proportion of hemoglobin molecules exist in the T-state at a given pO2.

*In fetal hemoglobin the central cavity is lined with more histidines than in adult hemoglobin, which results in preferential stabilization of the R-state. *This statement is false. Fetal hemoglobin has fewer histidine residues positioned in the central cavity than adult hemoglobin and this results in preferential stabilization of the R-state.

Fetal hemoglobin has a higher affinity for oxygen than maternal hemoglobin. Which of the following statements correctly outlines the mechanism behind this observation? In fetal hemoglobin, the residue Ser143 is mutated to His143, and so the protein binds BPG with greater affinity. In fetal hemoglobin, the residue His143 is mutated to Ser143, and so the protein binds BPG with greater affinity. In fetal hemoglobin, the residue Ser143 is mutated to His143, and so the protein binds BPG with lower affinity. In fetal hemoglobin, the residue His143 is mutated to Ser143, and so the protein binds BPG with lower affinity.

*In fetal hemoglobin, the residue His143 is mutated to Ser143, and so the protein binds BPG with lower affinity. *The mutation of His143 to Ser143 reduces the number of positively charged groups available to form salt bridges with BPG. This reduces the affinity of hemoglobin for BPG and thus the T (low-affinity) state of hemoglobin is less stable.

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

*Invariant residue.

Which of the following best describes the tertiary structure of myoglobin? It contains 8 -helices. It contains heme, which is slotted into a hydrophobic pocket between -helix E and -helix F. It contains no β-sheet. It is a heterotetramer. It contains heme, which is loosely associated via hydrophobic interactions with amino acid side chains in the heme pocket.

*It contains heme, which is slotted into a hydrophobic pocket between -helix E and -helix F. *Tertiary structure describes the precise atomic positioning of all atoms in a protein, including those in prosthetic groups.

During vigorous exercise, the pH of blood passing through skeletal muscle decreases. How does this decrease affect the behaviour of hemoglobin? It increases O2 binding to hemoglobin, because it decreases the binding of BPG. It decreases O2 binding to hemoglobin, because it decreases the binding of BPG. It increases O2 binding to hemoglobin, because it increases the binding of BPG. It decreases O2 binding to hemoglobin, because it increases the binding of BPG.

*It decreases O2 binding to hemoglobin, because it increases the binding of BPG. *As pH decreases, certain histidine side chains become positively charged and hemoglobin binds more BPG. This stabilizes the T state of the protein and decreases O2 binding (% saturation).

Which of the following is TRUE about the distal histidine of hemoglobin? It forms a strong covalent bond with the Fe2+ atom coordinated by heme. It is not conserved in myoglobin. It prevents helix F from moving in response to oxygen binding. It forms a hydrogen bond with bound oxygen. It covalently bonds heme into the hemoglobin subunit.

*It forms a hydrogen bond with bound oxygen. *The distal histidine (His E7) forms a hydrogen bond with bound oxygen.

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

*Its F-helix moves. *When one subunit of hemoglobin binds oxygen, a conformational change occurs in all four subunits, through cooperativity, and all four subunits adopt the R conformation. Thus the F-helix will move in the other -subunit, independently of oxygen binding.

Shown below are statements matching scientists with their accomplishments. Which of the statements below is INCORRECT: J. D. Bernal: Placed a crystal of the protein pepsin in an electron beam and obtained a diffraction pattern along with Dorothy Crowfoot Hodgkin. Max Perutz: In 1968 he reported the structure of hemoglobin at near atomic resolution. Archibald Hill: In 1910 he analyzed the sigmoidal oxygen dissociation curve of hemoglobin. John Kendrew: A colleague of Perutz who was also awarded the 1962 Nobel Prize in Chemistry.

*J. D. Bernal: Placed a crystal of the protein pepsin in an electron beam and obtained a diffraction pattern along with Dorothy Crowfoot Hodgkin. **J. D. Bernal: Placed a crystal of the protein pepsin in an X-ray beam and obtained a diffraction pattern along with Dorothy Crowfoot Hodgkin.

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 (K) for this reaction? K = [X][Y]/[XY] K = [XY]/[X][Y] K = [X] + [Y]/[X + Y] K = [XY]/[Y] K could not be determined with the information provided.

*K = [X][Y]/[XY]

Select the statement that best matches the following: Myosin Major component of the thick filament of the myofibril. Major component of the thin filament of the myofibril. Calcium binding protein. Functional unit of the myofibril. Chemical energy source for muscle contraction.

*Major component of the thick filament of the myofibril.

Select the statement that best matches the following: Actin Major component of the thick filament of the myofibril. Chemical energy source for muscle contraction. Major component of the thin filament of the myofibril. Calcium binding protein. Functional unit of the myofibril.

*Major component of the thin filament of the myofibril.

Shown below are statements matching scientists with their accomplishments. Which of the statements below is INCORRECT: Daniel Koshland: Proposed the sequential model of allosterism. Max Perutz: In 1945 hypothesized and in 1949 proved that sickle-cell anemia was the result of a mutant hemoglobin that had a less negative ionic charge than normal adult hemoglobin. This was the first evidence that a disease could result from an alteration in the molecular structure of a protein. Jacques Monod: Formulated the symmetry model of allosterism along with Jeffries Wyman and Jean-Pierre Changeux. Joseph Barcroft: In 1921 he anticipated the existence of BPG as a factor that decreased the oxygen affinity of hemoglobin. Christian Bohr: In 1904 he reported the release of protons upon oxygen binding by hemoglobin.

*Max Perutz: In 1945 hypothesized and in 1949 proved that sickle-cell anemia was the result of a mutant hemoglobin that had a less negative ionic charge than normal adult hemoglobin. This was the first evidence that a disease could result from an alteration in the molecular structure of a protein. **Linus Pauling did this.

Which of the following statements about blood diseases is not true: Mutations 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. Mutations that increase hemoglobin's O2 affinity lead to increased numbers of erythrocytes in order to compensate for the less than normal amount of O2 released in the tissues - a condition named polycythemia. Most mutations to hemoglobin observed in nature (i.e. hemoglobin variants) result in a lethal condition. Hemolytic anemia results from the lysis of erythrocytes. Cyanosis is caused by mutations that favor the oxidation of Fe(II) to Fe(III). 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. **The untrue statement is "Most mutations to hemoglobin observed in nature (i.e. hemoglobin variants) result in a lethal condition." Not all hemoglobin variants produce clinical symptoms, but some abnormal hemoglobin molecules do cause debilitating diseases.

Which of the following statements about diseases of hemoglobin and the blood is not true: The bluish skin color associated with cyanosis is due to the presence of methemoglobin in the arterial blood. 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. Cyanosis is caused by mutations that favor the oxidation of Fe(II) to Fe(III). Mutations to that destabilize hemoglobin's tertiary or quaternary structure, alter its oxygen-binding affinity (p50) and reduce its cooperativity result in diseased states. Hemolytic anemia results from the lysis of erythrocytes. 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.

*Most mutations to hemoglobin observed in nature (i.e. hemoglobin variants) result in a lethal condition. **The untrue statement is "Most mutations to hemoglobin observed in nature (i.e. hemoglobin variants) result in a lethal condition." Not all hemoglobin variants produce clinical symptoms, but some abnormal hemoglobin molecules do cause debilitating diseases.

Which of the following statements about the structure of myoglobin is FALSE? Myoglobin contains all three types of secondary structure. Myoglobin contains a heme prosthetic group that is slotted into a hydrophobic pocket between -helix E and -helix F. The tertiary structure of myogobin is a compact, roughly spherical shape. A heme prosthetic group is tightly bound to myoglobin via a coordination bond.

*Myoglobin contains all three types of secondary structure. *Myoglobin contains only two types of secondary structure, -helices and loops. It contains no β-sheet.

Which of the following statements most accurately explains why hemoglobin is able to deliver oxygen to myoglobin in the tissues? The pH of tissue/muscle is always higher than that of blood, which aids hemoglobin in giving up its oxygen. The presence of BPG in the red blood cells shifts the equilibrium towards the R state of hemoglobin. The iron in the heme group of myoglobin is Fe3+, which has a higher affinity for oxygen. Myoglobin has a hyperbolic oxygen binding curve, whereas hemoglobin has a sigmoidal oxygen binding curve.

*Myoglobin has a hyperbolic oxygen binding curve, whereas hemoglobin has a sigmoidal oxygen binding curve. *The sigmoidal binding curve illustrates hemoglobin's ability to adopt a low affinity state. This enables it to transfer oxygen to myoglobin which always binds oxygen with high affinity.

Myoglobin and hemoglobin are both oxygen-binding proteins but have very different physiological roles. Which two of the following are the most important factors that contribute to their different functions? The primary structure of myoglobin is completely different from that of hemoglobin. Myoglobin is a monomeric protein, whereas hemoglobin is a tetrameric protein. Hemoglobin binds BPG which stabilizes the deoxy (T) state. Myoglobin has a sigmoidal oxygen-binding curve whereas hemoglobin has a hyperbolic oxygen-binding curve.

*Myoglobin is a monomeric protein, whereas hemoglobin is a tetrameric protein *Hemoglobin binds BPG which stabilizes the deoxy (T) state.

If curve 3 represents the binding of oxygen to normal hemoglobin, which curve would represent the binding behaviour of a mutant hemoglobin that binds BPG irreversibly? 1 2 3 4 None of the above

*None of the above. *If hemoglobin bound BPG irreversibly it would be "fixed" in its low-affinity state. None of the binding curves shown here illustrates low-affinity binding.

Which of the following triggers the transition from T state to R state (low to high affinity) in hemoglobin? subunit dissociation. oxygen binding. movement of the proximal histidine. oxygen dissociation. heme binding.

*Oxygen binding. *When oxygen binds to the Fe(II) ion in the heme ring, at its 6th coordination position, the Fe(II) ion is pulled into the plane of the heme ring. It is this binding interaction that initiates the transition from T to R state.

Which of the following statements is FALSE regarding the interaction of oxygen with myoglobin? Oxygen binds at the 6th coordination position of the Fe2+ ion in the heme. Oxygen is a ligand of myoglobin. Oxygen is a homoallosteric effector of myoglobin. Oxygen binds reversibly and with high affinity to the heme prosthetic group.

*Oxygen is a homoallosteric effector of myoglobin. *This statement is false. Myoglobin is not an allosteric protein.

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

*Quaternary structure. *Myoglobin does not have quaternary structure whereas hemoglobin does.

Which of the following statements about sickle cell anemia is FALSE? The mutation in sickle cell anemia replaces a hydrophilic surface residue with a non-polar residue. In sickle cell anemia, hemoglobin molecules aggregate to form long fibers that distort the shape of the red blood cell. Sickle cell anemia is a consequence of a conservative mutation in the β-globin gene. Sickle cell anemia is a genetic disease.

*Sickle cell anemia is a consequence of a conservative mutation in the β-globin gene. *A mutation that significantly affects the folding or function of a protein cannot be considered conservative.

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

*Subunit interfaces in hemoglobin are composed of predominantly salt bridges. **These interfaces are predominantly hydrophobic.

Which of the following statements about the T and R states of hemoglobin is FALSE? 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 R state has a smaller central cavity than the T state. In the R state, the Fe2+ ion lies in the plane of the heme.

*The T state is less stable than the R state at lower pH. *This statement is false. Lower pH reflects an increased concentration of H+ ions, and the T state of hemoglobin is stabilized under these conditions.

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? The T state would be less stable. Oxygen binding would be more sensitive to pH. The T state would be more stable. Oxygen binding would be less sensitive to pH.

*The T state would be less stable. *The replacement of Lys with Ser would reduce the affinity of hemoglobin for BPG and the T state would be less stable.

Which of the following statements about 2,3 bisphosphoglycerate (BPG) is TRUE? BPG binds more tightly to fetal hemoglobin than to adult hemoglobin. BPG binds at a site which contains multiple negatively-charged groups. BPG lowers myoglobin's affinity for oxygen. 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. *This statement is true. In hemoglobin, the positively-charged N-terminal groups of the two β subunits are involved in BPG binding. If these groups were modified to make them uncharged, then the binding affinity for BPG would be reduced.

Which of the following statements about hemoglobin is TRUE? Variations in the primary structure of hemoglobin always result in genetic diseases. 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. In the Bohr effect the binding of oxygen to hemoglobin is increased by the presence of H+ ions and CO2.

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

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+.

*The central cavity becomes smaller.

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 has a lower K (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 left because hemoglobin binds oxygen more tightly.

*The curve is shifted to the right, because hemoglobin has a lower affinity for oxygen. *An increased concentration of BPG in red blood cells favours formation of the T, low-affinity state of hemoglobin and so the oxygen-binding curve will shift to the right.

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

*The distal histidine occupies the 6th coordination position of Fe2+. *This statement does not describe a role for histidine in hemoglobin. The 6th coordination position of the Fe(II) ion is occupied reversibly by oxygen.

Which of the following statements correctly describes the interaction between an allosteric protein and an allosteric effector? The effector binds non-specifically to one subunit and through induced fit initiates cooperativity between the subunits. The effector activates the protein by causing it to switch from its T (low affinity) to R (high affinity) form. 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 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. 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. 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 false statement is "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." In fact, because of the beneficial effects of positive cooperativity, the fourth O2 molecule binds with 100-fold greater affinity than the first.

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 primary, secondary and tertiary structure, but not quaternary. The dissociation constant (K) of the ligand is low. The protein has a constant high affinity for the ligand. The protein binds the ligand cooperatively.

*The protein binds the ligand cooperatively. *A sigmoidal-shaped binding curve typically indicates cooperative binding behaviour.

A newly-identified protein shows a sigmoidally-shaped curve in a graph of fractional saturation versus ligand concentration. Which of the following statements about that protein is TRUE? The protein undergoes conformational changes in quaternary structure when the ligand binds. The protein does NOT bind the ligand cooperatively. When the ligand binds to one subunit, the affinity of the other subunits for the same ligand remains the same. The ligand binds irreversibly at a specific site on the protein, causing a global change in shape.

*The protein undergoes conformational changes in quaternary structure when the ligand binds.

If hemoglobin is in the 'T' state, what is the first component of the peptide chain that moves in response to oxygen binding? The heme group The distal histidine The Fe2+ ion The proximal histidine

*The proximal histidine.

Why does the concentration of BPG in red blood cells increase when humans are exposed to high altitudes? To induce the production of more red blood cells. To neutralize the increased concentration of hydrogen ions produced when muscle works harder at high altitudes. To allow hemoglobin to release more oxygen at lower partial pressures of oxygen. To allow hemoglobin to bind more oxygen at lower partial pressures of oxygen.

*To allow hemoglobin to release more oxygen at lower partial pressures of oxygen. *When the partial pressure of oxygen in the lungs is low, the oxygen-saturation of hemoglobin is reduced. This means that there is less total oxygen available for release in the tissues. One way to compensate for this shortfall is to ensure that hemoglobin releases relatively more oxygen in the tissues than usual and this is achieved by increasing the concentration of BPG in the red blood cells.

Calcium modulates muscle activity through binding to the thin filament protein troponin C. True False

*True

Myoglobin increases the effective solubility of oxygen in muscle cells. False True

*True

p50, or oxygen tension, is the oxygen pressure (pO2) at which hemoglobin or myoglobin is 50% saturated with oxygen. False True

*True

What is the basic subunit structure of immunoglobulins? One light chain and one heavy chain. Two identical heavy chains. Two identical light chains and two identical heavy chains. Two identical light chains.

*Two identical light chains and two identical heavy chains. **Some immunoglobulins contain multiple copies of this basic unit.

A newly-identified protein shows the following behaviour in ligand binding. Which of the statements about this protein is FALSE? When the ligand binds to one subunit, the affinity of the other subunits for the same ligand is reduced. The protein binds the ligand cooperatively. The ligand binds reversibly at a specific site on the protein, causing a global change in conformation. The protein exists in two conformational states which have different affinities for the ligand.

*When the ligand binds to one subunit, the affinity of the other subunits for the same ligand is reduced. *This statement is false. This curve indicates that the binding of ligand to one subunit increases the affinity of the other subunits for the same ligand.

The immune response is triggered by the presence of foreign macromolecules, called ________.

*antigens

The secondary structure of myoglobin consists of ________ α-helices and the connecting loops.

*eight

IgG is the most common class of ________.

*immunoglobulins

Muscle fibers are composed of parallel bundles of ________.

*myofibrils

Thick filaments in vertebrates are composed mostly of a single protein called ________.

*myosin

In striated muscle, the longitudinal axis of the fiber is ________ to the striations.

*perpendicular

The removal of actin monomers at one end of a microfilament, and their addition at the other end is known as ________.

*treadmilling

Which of the following represents the true protomer of hemoglobin? α β {α}2 β2 α β

*α β

The ability of an antibody to recognize antigens resides in three loops in the variable domain of the immunoglobulin fold. The basic immunoglobulin structure must accommodate an enormous variety of antigens. Most of the amino acid variation among antibodies is concentrated in these three short segments, called hypervariable sequences that line an immunoglobulin's antigen-binding site, so that their amino acids determine its binding specificity. True False

*True