wiley ch.7 hw

Cyanosis is caused by mutations that favor the oxidation of Fe___ to Fe___.

2+ 3+

The quaternary structure of hemoglobin consists of __ polypeptide chains.

4

Which of the following statements about BPG and its effect on oxygen transport is NOT true: An initial 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 elevated 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 altidude and veinous pO2

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 _______ effect.

Bohr

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

______________ gives red blood cells their color.

Hemoglobin

Which of the statements below about hemoglobin's oxygen binding is INCORRECT: 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.

Which of the following statements about diseases of hemoglobin and the blood is not true: 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.

Under physiological conditions, hemoglobin releases ~ 0.6 protons for each bound ____.

O2

__________ _________ 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.

Oxygen binding

Daniel Koshland: ____________ the sequential model of allosterism.

Proposed

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

Quaternary

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 __ state of hemoglobin is favored relative to the __ state, and so the oxygen-binding curve will shift to the left.

R T

The __ --> __ transition in hemoglobin subunits explains the difference in the oxygen affinities of oxy- and deoxyhemoglobin.

T ---> R

Which of the statements below about hemoglobin is INCORRECT: Subunit interfaces in hemoglobin are composed of predominantly salt bridges.

These interfaces are predominantly hydrophobic.

The mutation causing sickle cell anemia is that hemoglobin S contains _____ rather than ____ at the sixth position of each beta chain.

Val Glu

The cooperative binding of O2 by hemoglobin is an example of an ____________ 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.

allosteric

Jacques Monod: Formulated the symmetry model of _____________ along with Jeffries Wyman and Jean-Pierre Changeux.

allosterism

Which of the following represents the true protomer of hemoglobin? - ______ ______

alpha, beta

The bluish skin color associated with ___________ is due to the presence of methemoglobin in the arterial blood.

cyanosis

Joseph Barcroft: In 1921 he anticipated the existence of BPG as a factor that ____________ the oxygen affinity of hemoglobin.

decreased

The presence of BPG in mammalian erythrocytes ____________ hemoglobin's affinity for oxygen.

decreases

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

decreases increases

Mutations to that _________________ hemoglobin's tertiary or quaternary structure, alter its oxygen-binding affinity (p50) and reduce its cooperativity result in diseased states.

destabilize

Hemolytic anemia results from the lysis of ________________.

erythrocytes.

Individuals who are _______________ carriers of hemoglobin S in an area where malaria is prevalent are more likely to survive to maturity than individuals who are ______________ for normal hemoglobin.

heterozygous homozygous

CO2 also modulates O2 binding to hemoglobin by allosterically binding the T state but not the R state:Thus when the CO2 concentration is ______, as it is in the capillaries, it stabilizes T state, stimulating hemoglobin to release its bound O2.

high

The administration of ________________ is an effective treatment for sickle-cell anemia.

hydroxyurea

Mutations that ____________ 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.

increase

The reason for the Bohr effect on the molecular level is because in hemoglobin's T-state, the formation of ion pairs ____________ the pK values of certain groups whereas these ion pairings are _________ in its R-state and the pK's of the groups ___________ (making them more ___________ and more likely to give up protons).

increases absent decrease acidic

Sickle-cell anemia is caused from deoxyhemoglobin S forming ______________ filaments.

insoluble

Shown below are statements matching scientists with their accomplishments. Which of the statements below is INCORRECT: 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.

is incorrect b/c Linus Pauling did this.

Hemoglobin is part of an oxygen delivery system that is needed for animals that are too_______ for oxygen to be delivered by simple diffusion.

large

The binding of oxygen to hemoglobin in an example of positive cooperativity: Oxygen binding favors the T --> R transition switching hemoglobin from the _____ affinity for oxygen T-state to the ______ affinity for oxygen R-state.

low high

Why is hemoglobin's affinity for oxygen sensitive to small changes in pH (the Bohr effect)? -Histidine side chains in hemoglobin become charged at ________ pH forming salt bridges that stabilize the ___ state.

lower T

The Bohr effect involves the O2 affinity of hemoglobin increasing with increasing pH. Thus increasing the pH stimulates hemoglobin to bind ________ oxygen.

more

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 ___________ allosteric effect on hemoglobin's binding of oxygen.

negative

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 _____ subunit.

one

It has been dubbed an "honorary enzyme" even though it functions in ___________ transport and does not catalyze a chemical reaction.

oxygen

The effects of BPG also help supply the fetus with oxygen. A fetus obtains its O2 from the maternal circulation via the _____________. BPG binds more tightly to _______ hemoglobin than to ________ hemoglobin thus facilitating the transfer of O2 to the fetus.

placenta adult fetal

Christian Bohr: In 1904 he reported the release of __________ upon oxygen binding by hemoglobin.

protons

Myoglobin does not have ________________ structure whereas hemoglobin does.

quaternary

Long-distance runners prefer to train at high altitude even when the race is to be held at sea level. High-altitude adaptation includes the production of additional _____ _________ cells, which would ___________ the oxygen-delivery capacity of the body at both high and low altitude. The production of _____ _______ cells requires several weeks, so a day or two at high elevation would not provide much advantage for the runner.

red blood or (erythrocyte) increase red blood or (erythrocyte)

Hemoglobin's sigmoidal oxygen binding curve is due to the T --> R transition: The ______________ 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.

sigmoidal

Most of the variant hemoglobins identified result from a ________ amino acid substitution in a globin polypeptide chain.

single

What happens when hemoglobin is converted from the deoxy(T) form to the oxy (R) form? -The central cavity becomes ____________.

smaller

Hemoglobin is a __________ made up of myoglobin-like subunits.

tetramer

BPG stands for D-2,3 bisphosphoglycerate true or false.

true