Myo and Hemoglobin

What are negative allosteric effectors of hemoglobin?

Negative allosteric effectors of hemoglobin include protons (H⁺), carbon dioxide (CO₂), and 2,3-BPG. Oxygen (O₂) is not a negative allosteric effector.

How many ligands can iron bind in myoglobin?

Iron can bind to 6 ligands at a time, with the respective ligands being His F8 and O₂.

True or false: α1β2 and α2β1 are responsible for subunit packing.

False; α1β1 and α2β2 are responsible for subunit packing.

Why does myoglobin not exhibit changes to K₀.₅ in the presence of CO₂, protons, or BPG?

Because myoglobin is monomeric and does not undergo T ↔ R transitions.

What is myoglobin with Fe³⁺ called?

Metmyoglobin.

When oxygen is bound to myoglobin, how is it oriented relative to the heme plane?

It is tilted relative to a perpendicular to the heme plane.

What happens to K₀.₅ when hemoglobin binds to 2,3-BPG?

K₀.₅ increases, indicating a decrease in affinity.

Under the Bohr effect, what happens to hemoglobin’s K₀.₅?

K₀.₅ increases because hemoglobin’s affinity for oxygen decreases.

Why does fetal hemoglobin (HbF) bind 2,3-BPG less tightly than adult hemoglobin?

Fetal hemoglobin replaces His143 with Ser in the γ-chains, reducing positive charge in the BPG-binding cavity.

What happens to the oxygen-binding curve of fetal hemoglobin compared to adult hemoglobin?

It shifts to the left, indicating a higher affinity for oxygen.

What is true regarding 2,3-BPG?

It is a negative allosteric effector of hemoglobin, and its binding site is distant from the iron where O₂ binds.

How many salt bridges are formed in three amino acid residues of deoxyhemoglobin?

Two salt bridges are formed.

What is the partial pressure of O₂ in the lungs when hemoglobin becomes saturated?

100 torr.

What type of curve does myoglobin obey?

Myoglobin obeys a Michaelis-Menten-type (hyperbolic) curve.

What is true regarding heme groups?

Heme is a prosthetic group.

Which statement is FALSE regarding fetal hemoglobin?

Fetal hemoglobin has γ-chains that do not contain His143.

True or false: Allostery and cooperativity can be explained by the KNF and MWC models.

True.

Which His induces the R-to-T transition of hemoglobin?

His146.

What is true regarding hemoglobin?

Hemoglobin binds oxygen in the lungs and transports oxygen to tissues.

What is the Bohr effect?

The Bohr effect describes how decreased pH (increased H⁺) promotes oxygen release by stabilizing the T-state of hemoglobin.

How does CO₂ promote oxygen release from hemoglobin?

CO₂ forms carbamate groups with terminal amino groups, stabilizing the T-state.

What metal do myoglobin and hemoglobin use to bind oxygen?

Ferrous iron (Fe²⁺).

What is the physiological role of 2,3-BPG in oxygen transport?

It stabilizes the T-state of hemoglobin, promoting O₂ release in tissues.

Why does fetal hemoglobin have a higher affinity for oxygen than adult hemoglobin?

Fetal hemoglobin has γ-chains that bind BPG less effectively, reducing T-state stabilization and increasing O₂ affinity.

What happens to the Fe²⁺ ion in hemoglobin upon oxygen binding?

It moves approximately 0.04 nm closer to the plane of the heme, inducing conformational changes transmitted to the subunits.

What happens to the oxygen-binding curve of hemoglobin during alkalosis?

The affinity for O₂ increases, and the curve shifts to the left.

What is the Hill coefficient (n) of hemoglobin?

The Hill coefficient of hemoglobin is approximately 2.8, indicating positive cooperativity.

When O₂ binds to ferrous iron in heme, what is its conformation?

It is about 60° with respect to the perpendicular to the heme plane.

In the MWC model, what does L represent?

L is the ratio of T₀ to R₀ (the equilibrium between T and R states in the absence of ligand).

A negative effector binds preferentially to which conformation of the enzyme in an MWC K-system?

The T form.

What happens to myoglobin when the iron in its heme is oxidized from Fe²⁺ to Fe³⁺?

It cannot bind oxygen at all; the oxidized form is called metmyoglobin.

When a negative allosteric effector stabilizes the T form in a K-system, which of the following occurs?

K₀.₅ increases (the binding curve shifts to the right).

In V-systems, which property changes in the presence of allosteric effectors?

Vmax.

In V-systems, why does K₀.₅ remain unchanged?

R and T forms have the same affinity for substrate.

In a K-system, what is the defining feature of regulation?

K₀.₅ changes in response to allosteric effectors.

In the presence of a positive effector, what happens to a K-system’s binding curve?

It shifts to the left (increased affinity; lower K₀.₅).

Inhibitors binding to the T state do what to substrate binding affinity?

They decrease substrate binding affinity.

In a V-system, when cellular [S] is much greater than K₀.₅, regulation depends primarily on what?

Catalytic differences between the R and T forms (differences in Vmax).

Which of the following correctly compares hemoglobin and myoglobin? A. Hemoglobin is monomeric with one heme group; myoglobin is tetrameric with four heme groups. B. Hemoglobin is tetrameric with four heme groups; myoglobin is monomeric with one heme group. C. Both are tetrameric and show identical cooperativity. D. Both are monomeric and follow a sigmoidal binding curve.

B. Hemoglobin is tetrameric with four heme groups; myoglobin is monomeric with one heme group.

What is the difference between the oxygen-binding curves of hemoglobin and myoglobin? A. Both show hyperbolic curves due to identical heme-heme interactions. B. Hemoglobin shows a sigmoidal curve due to cooperativity, while myoglobin shows a hyperbolic curve. C. Myoglobin shows a sigmoidal curve due to the Bohr effect. D. Both follow a sigmoidal curve because they are allosteric proteins.

B. Hemoglobin shows a sigmoidal curve due to cooperativity, while myoglobin shows a hyperbolic curve.

True or false: Hemoglobin and myoglobin are enzymes.

False.

True or false: In oxygen binding to myoglobin, the fifth ligand is donated by the imidazole side chain of the 8th amino acid residue histidine on the F (6th) helix.

True.

In the KNF (sequential) model for hemoglobin cooperativity: A. All subunits switch from T to R simultaneously. B. Binding of O₂ to one subunit induces conformational change in adjacent subunits, increasing their affinity. C. Each subunit binds O₂ independently with no conformational change. D. O₂ binding causes complete tetramer dissociation.

B. Binding of O₂ to one subunit induces conformational change in adjacent subunits, increasing their affinity.

Which of the following best describes the Bohr effect? A. Proton binding increases hemoglobin's affinity for oxygen. B. Decreased pH promotes oxygen release by stabilizing the T-state. C. Oxygen binding promotes proton uptake and stabilizes the T-state. D. The Bohr effect occurs only at high pH and high O₂ pressure.

B. Decreased pH promotes oxygen release by stabilizing the T-state.

CO₂ promotes oxygen release from hemoglobin by: A. Competing with O₂ for heme iron. B. Forming carbamate groups with terminal amino groups, stabilizing the T-state. C. Inhibiting 2,3-BPG binding. D. Causing denaturation of globin chains.

B. Forming carbamate groups with terminal amino groups, stabilizing the T-state.

Upon oxygen binding, the Fe²⁺ ion in hemoglobin moves approximately 0.04 nm closer to the plane of heme, which: A. Has no significant effect on tertiary or quaternary structure. B. Induces large conformational changes transmitted to adjacent subunits, increasing O₂ affinity. C. Disrupts heme-heme interactions, decreasing affinity. D. Stabilizes the salt bridges between the subunits.

B. Induces large conformational changes transmitted to adjacent subunits, increasing O₂ affinity.

During alkalosis (serum pH > 7.45), what happens to the oxygen-binding curve of hemoglobin? A. Affinity for O₂ increases; the curve shifts left. B. Affinity for O₂ increases; the curve shifts right. C. Affinity for O₂ decreases; the curve shifts left. D. Affinity for O₂ decreases; the curve shifts right.

A. Affinity for O₂ increases; the curve shifts left.

The transition of hemoglobin from the T (deoxy) state to the R (oxy) state is characterized by: A. The formation of new salt bridges to stabilize the R state. B. A 90° rotation of the α1β1 dimer relative to the α2β2 dimer. C. The permanent oxidation of iron from Fe²⁺ to Fe³⁺. D. The breaking of eight salt bridges that stabilize the T state.

D. The breaking of eight salt bridges that stabilize the T state.

According to the lecture, the heme group consists of a Protoporphyrin IX ring structure chelated to a single ion of: A. Ferric iron (Fe³⁺). B. Ferrous iron (Fe²⁺). C. Magnesium (Mg²⁺). D. Copper (Cu²⁺).

B. Ferrous iron (Fe²⁺).

Besides producing H⁺ via the hydration of CO₂, how else does carbon dioxide favor the T (deoxy) state? A. It binds directly to the heme iron, competing with O₂. B. It binds to the His F8 residue, blocking the conformational change. C. It reacts with terminal amino groups to form carbamates, which form salt bridges that stabilize the T state. D. It acts as a positive allosteric effector for the R state.

C. It reacts with terminal amino groups to form carbamates, which form salt bridges that stabilize the T state.

The sigmoidal binding curve of hemoglobin is experimentally determined to have a Hill coefficient (n) of 2.8. This value indicates: A. That all four sites bind oxygen simultaneously (n = 4). B. A complete lack of cooperative interaction between subunits (n = 1). C. A significant degree of positive cooperativity, but not a perfect “all-or-nothing” (n = 4) event. D. That hemoglobin follows a simple Michaelis-Menten binding model (n = 1).

C. A significant degree of positive cooperativity, but not a perfect “all-or-nothing” (n = 4) event.

2,3-BPG stabilizes the T (deoxy) state of hemoglobin by binding to a central cavity between the two β-subunits. Its negatively charged groups interact with several positive charges provided by: A. The four heme groups. B. Lysine, histidine, and the N-termini. C. The α1β1 and α2β2 contact interfaces. D. Serine residues at position 143.

B. Lysine, histidine, and the N-termini.

The Bohr effect, which promotes oxygen release in tissues, is molecularly stabilized in the T-state by: A. The binding of O₂ to the His F8 residue. B. The binding of 2,3-BPG to the α-subunits. C. The protonation of His146, allowing it to form a salt bridge that stabilizes the deoxy form. D. The hydration of carbamates at the N-termini.

C. The protonation of His146, allowing it to form a salt bridge that stabilizes the deoxy form.

Salt bridges stabilize which structural level of the T state of deoxyhemoglobin? A. Primary. B. Secondary. C. Tertiary. D. Quaternary.

D. Quaternary.

Deoxymyoglobin is oxidized to yield: A. Fe. B. Fe⁺. C. Fe²⁺. D. Fe³⁺.

D. Fe³⁺.

Fetal γ-chains have Ser instead of His at position ___ and thus lack two of the positive charges in the BPG-binding cavity: A. 146. B. 143. C. 141. D. 148.

B. 143.

The protonation of which His induces the R-to-T transition of hemoglobin? A. 143. B. 94. C. 141. D. 146.

D. 146.

What is the partial pressure of O₂ in the lungs when it becomes saturated with O₂? A. 100 torr. B. 40 torr. C. 60 torr. D. 80 torr.

A. 100 torr.