1st Unit / Ch 3 Globular Proteins Flashcards
Myoglobin Structure and Function 3.1
Which His residue (A or B), as shown, is the proximal His? What is its function?
What is special about the location of this amino acid?
Choice A is the proximal His. It forms a coordination bond with the Fe 2 in the heme prosthetic group. Polar His is located in the nonpolar crevice where heme binds.
Myoglobin Structure and Function 3.1
What type of secondary structure is most abundant in Mb? Does Mb have a
quaternary structure?
Mb is rich in a -helices. Because it is a monomeric protein, Mb does not have a quaternary structure.
Myoglobin Structure and Function 3.1
Rhabdomyolysis (muscle destruction) caused by trauma, for example, is
characterized by muscle pain, muscle weakness, and dark-colored urine. The dark color of the urine is the result of excretion of , a condition known as.
Rhabdomyolysis (muscle destruction) caused by trauma, for example, is
characterized by muscle pain, muscle weakness, and dark-colored urine (shown). The dark color of the urine is the result of excretion of Mb , a condition known as myoglobinuria.
Hemoglobin Structure and Function 3.2
Which form of Hb (deoxygenated or oxygenated) is referred to as the R form? What determines the equilibrium concentrations of deoxyHb and oxyHb?
The oxygenated, high-O 2 -affinity form of Hb is referred to as the R form. The availability of O 2 determines the equilibrium concentrations.
Hemoglobin Structure and Function 3.2
How does the structure of Hb change as O 2 binds to the heme Fe 2?
The binding of O2 to the heme Fe2+ pulls the F 2+ into the plane of the heme. This causes salt bridges between the two a.b dimers to rupture, thereby allowing movement that converts the T to the R form.
Hemoglobin Structure and Function 3.2
What condition, characterized by a “ chocolate cyanosis ,” results from the oxidation of Fe 2+ to Fe 3 + in Hb? Why might replacement of the distal His cause this condition?
Methemoglobinemia, characterized by a “chocolate cyanosis” (dark-colored blood, bluish colored skin), results from the oxidation of Fe 2+ to Fe 3+ in Hb. Because the distal His stabilizes the binding of O 2 to the heme Fe 2+ , its replacement with another amino acid will favor oxidation of Fe 2+ to Fe 3+ and decreased binding of O2 .
O2 Binding to Myoglobin and Hemoglobin 3.3
Use the figure to determine the approximate amount of O2 that would be delivered by Mb and Hb when the pO 2 in the capillary bed is -26 mm Hg.
At a pO2 of 26 mm Hg, Hb would have delivered 50% of its O2 , while Mb would have delivered only 10%. Hb has a lower O 2 affinity at all pO2 values and a higher P 50 than does Mb, as shown. [ Note: P 50 is that pO 2 required to achieve 50% saturation of the
O 2 -binding sites.]
O2 Binding to Myoglobin and Hemoglobin 3.3
Why is the O 2 -dissociation curve for Hb sigmoidal and that for Mb hyperbolic?
Hb is a tetramer. The O2 -dissociation curve for Hb is sigmoidal because the four subunits cooperate in binding O2 . The fi rst O2 binds to Hb with low affi nity. As subsequent
subunits become occupied with O2 , the affi nity increases such that the last O2 binds with relative ease. Because Mb is a monomeric protein, it does not show cooperativity. Consequently,
its O2 -dissociation curve is hyperbolic , not sigmoidal.
O2 Binding to Myoglobin and Hemoglobin 3.3
How might RBC production be altered to compensate for changes to Hb that result in an abnormally high affinity for O2 ?
RBC production typically is increased (a process known as erythrocytosis) to compensate for changes to Hb that result in an abnormally high affi nity for O2 : more RBCs = more Hb =
more O2 carried.
Allosteric Effects 3.4
Which curve (A or B), as shown, represents the lower pH?
Curve B represents the lower pH (higher H+ concentration).
Allosteric Effects 3.4
List two other allosteric effectors that, when increased, result in a rightward shift of the Hb O 2 -dissociation curve. What does this shift refl ect? Do these allosteric effectors stabilize the R or the T form of Hb?
Increased amounts of CO 2 and 2,3-BPG also result in a rightward shift
of the Hb O2 -dissociation curve. The shift refl ects increased off-loading
(delivery) of O2 to the tissues. These allosteric effectors stabilize the
T ( deoxygenated ) form of Hb, enabling O 2 delivery.
Allosteric Effects 3.4
How does the binding of CO 2 to Hb stabilize Hb’s deoxygenated form?
When CO 2 binds to the amino termini of the four Hb subunits, forming
carbaminohemoglobin, the negative charge is used to form a salt
bridge that helps to stabilize Hb’s deoxygenated (T) form.
Allosteric Effects 3.4
What is the Bohr effect?
The Bohr effect refers to the increase in O2 delivery when CO2 or H +
increases. In actively metabolizing tissue, Hb binds CO2 and H+ and
releases O2. The process is reversed in the lungs.
Minor Hemoglobins 3.5
How does the subunit composition of HbF, as illustrated, infl uence the O 2 affinity of HbF?
HbF contains 2+ and 2 + subunits. Relative to the b subunits, the y subunits have a reduced affi nity for 2,3-BPG. This results in HbF having an increased affi nity for O2. [ Note: HbF is needed to obtain O2 from maternal HbA, and
its increased affi nity for O2 enables this process.]
Minor Hemoglobins 3.5
What form of Hb replaces HbF, and when does this occur?
HbF is the major Hb found in the fetus and the newborn but represents 2% of the Hb in most adults because it is
replaced by HbA (2 a and 2 b subunits) by about 6 months after birth.
Hemoglobinopathies 3.6
How do the sickled RBCs illustrated cause infarction (cell/tissue death due to obstruction of blood flow)?
Sickled RBCs cause infarction
because the rigid polymer of HbS makes
the sickled cells less deformable than
the nonsickled cells and, therefore, less
able to move through blood vessels. This
can cause a blockage that obstructs the
delivery of O 2 .
