Module 5: Myoglobin and Hemoglobin Flashcards

Comprehensive flashcards covering protein dynamics, myoglobin and hemoglobin structure/function, allosteric regulation, the Bohr Effect, and molecular diseases based on Module 5 lecture notes.

What characterizes dynamic proteins compared to static ones in terms of structure and function?

Dynamic proteins possess structural flexibility and can undergo conformational changes influenced by interactions with ligands to perform unique functions.

What is a ligand in the context of protein function?

A molecule that is reversibly bound by a protein, which can include other proteins.

How does the binding site of a protein relate to its ligand?

The binding site is complementary to the ligand in terms of shape, charge, hydrophobicity, and hydrogen-bonding potential.

What is 'induced fit'?

A conformational change in a protein's structure caused by ligand binding that often results in a change in function.

Why are specialized proteins and heme groups necessary for oxygen transport and storage?

Oxygen has low solubility in aqueous solutions, amino acid side chains cannot bind it reversibly, and free transition state metals produce damaging free radicals.

What is the primary physiological role of Myoglobin ($Mb$)?

It is a monomeric protein that facilitates oxygen storage in peripheral tissues.

What is the primary physiological role of Hemoglobin ($Hb$)?

It is a tetrameric protein found in red blood cells that transports oxygen from the lungs to the periphery.

According to the transcript, how does available oxygen affect insect size?

Insects grown in the presence of elevated oxygen can achieve greater sizes because available oxygen limits organism size.

What are the components of a heme prosthetic group?

A protoporphyrin ring system bound to a single ferrous ($Fe^{2+}$) iron atom.

Why is it important that iron remains in the $Fe^{2+}$ state for oxygen binding?

$Fe^{2+}$ binds $O_2$ reversibly, whereas $Fe^{3+}$ (ferric iron) does not bind $O_2$.

What provides the four coordinating interactions for the iron atom within the heme ring?

Nitrogen atoms within the protoporphyrin ring system, whose electron-donating characteristics prevent the conversion of $Fe^{2+}$ to $Fe^{3+}$.

What molecules occupy the fifth and sixth coordination positions of iron in myoglobin/hemoglobin?

The fifth position is an imidazole group of a proximal histidine residue; the sixth position is for $O_2$ binding.

What is the role of the distal histidine in the heme pocket?

It provides a stabilizing interaction for the bound $O_2$ molecule.

Why is Carbon Monoxide ($CO$) toxic to humans?

It competes with oxygen for binding to heme and has a $200$ times greater affinity for heme than $O_2$.

How many oxygen molecules can one hemoglobin molecule bind compared to one myoglobin molecule?

Hemoglobin can bind four oxygen molecules (due to four subunits/hemes), while myoglobin can bind only one (single subunit/heme).

Contrast the oxygen binding curves of myoglobin and hemoglobin.

Myoglobin displays a hyperbolic curve, while hemoglobin displays a sigmoidal curve indicative of cooperative binding.

What was the first protein structure determined by x-ray crystallography?

Sperm whale myoglobin, determined by John Kendrew.

What is the $P_{50}$ value for myoglobin, and what does it signify?

The $P_{50}$ is $3\,torr$, representing the partial pressure of oxygen required to half-saturate the protein.

Calculate the fractional saturation ($\theta$) of myoglobin in peripheral tissues where $pO_2$ is $20\,torr$.

$\theta = 20 / (20 + 3) = 87\%$ saturation.

Define the T and R states in allosteric proteins.

The T (tense) form is the inactive state, and the R (relaxed) form is the active state; they exist in rapid equilibrium.

Distinguish between homotropic and heterotropic modulators.

Homotropic interactions occur when the normal ligand and modulator are the same; heterotropic interactions occur when the modulator is different from the normal ligand.

How does oxygen act as an allosteric activator for hemoglobin?

It acts as a homotropic activator where the binding of the first $O_2$ promotes the R state, making it easier for subsequent $O_2$ molecules to bind (positive cooperativity).

What structural change occurs in heme iron when transitioning from the T to R state?

In the T state, the iron atom sits just outside the heme ring plane; upon oxygen binding (R state), the iron moves into the plane of the ring.

Why is hemoglobin's sigmoidal binding curve physiologically significant in the periphery?

It allows hemoglobin to release over half its oxygen load at the partial pressures found in the periphery, making it sensitive to regions at risk for hypoxia.

What role does 2,3-Bisphosphoglycerate (2,3 BPG) play in hemoglobin function?

It is a heterotropic allosteric inhibitor that binds to a positively charged pocket in deoxyhemoglobin to decrease oxygen affinity and facilitate oxygen release.

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

Fetal Hb has a lower affinity for the inhibitor 2,3 BPG because a $His143$ residue is replaced by $Ser$, reducing the positive charge in the binding pocket.

How does the body adapt to high altitudes using 2,3 BPG?

Increased production of 2,3 BPG decreases hemoglobin's oxygen affinity to ensure sufficient oxygen delivery to tissues despite lower atmospheric oxygen.

Define the Bohr Effect.

The pH dependence of hemoglobin's affinity for $O_2$, where lower pH (increased acidity) decreases oxygen affinity to promote release to active tissues.

What is the function of carbonic anhydrase in relation to oxygen delivery?

It converts $CO_2$ into bicarbonate and a proton; the resulting decrease in pH triggers the Bohr Effect to release oxygen from hemoglobin.

What is carbaminohemoglobin?

A form of hemoglobin where $CO_2$ is covalently linked to the N-terminus as a carbamate; this form has a lower oxygen affinity.

What is the molecular basis for Sickle Cell Anemia?

A genetic mutation resulting in a single amino acid change ($Glu6Val$) that causes deoxyhemoglobin ($HbS$) to aggregate into fibers.

Why does the sickle cell trait ($HbS$) provide a selection advantage against malaria?

Malaria infection lowers the pH in red blood cells, causing $HbS$ to form fibers and deform the cell; these deformed cells are then destroyed by the spleen, limiting the infection.

Compare hemocyanin to hemoglobin regarding their metal centers and oxygen binding.

Hemocyanin uses two copper atoms rather than iron, has no heme ring, and is not localized within specialized transport cells.