Recitation Case Studies

Chloride ions (Cl^-) cannot cross the lipid bilayer of cell membranes by simple diffusion. Which of the following best explains why?

• Cl- is too large to fit between the phospholipid head groups.

• Cl- is nonpolar and therefore repelled by the polar head groups.

• Cl- binds irreversibly to cholesterol in the membrane.

• Cl- reacts with the fatty acid tails and is chemically destroyed.

• Cl- is a charged ion, and the hydrophobic interior of the bilayer creates an energy barrier to the passage of charges.

• Cl- is a charged ion, and the hydrophobic interior of the bilayer creates an energy barrier to the passage of charges.

CFTR is classified as an integral membrane protein belonging to the ABC transporter superfamily. Which of the following best describes how CTFR is oriented in the membrane? 

• It is a soluble protein that temporarily associates with the membrane when chloride needs to be transported.

• It is a peripheral membrane protein attached to the outer surface by electrostatic interactions.

• It is anchored to the membrane by a single GPI lipid anchor on the extracellular side.

• It sits entirely within the lipid bilayer without any portions exposed to either the cytoplasm or the extracellular space.

• It spans the membrane multiple times with 12 transmembrane α-helices, with domains on both sides of the bilayer.

• It spans the membrane multiple times with 12 transmembrane α-helices, with domains on both sides of the bilayer.

The ΔF508 mutation deletes a single phenylalanine from CFTR’s first nucleotide-binding domain. Over 98% of ΔF508-CFTR is degraded before it leaves the ER. Which of the following best explains why this one amino acid deletion causes the entire protein to be destroyed?

• The deletion disrupts protein folding. The ER quality control system recognizes the misfolded protein and targets it for degradation before it can reach the cell surface.

• Phenylalanine 508 is required for the signal peptide to direct the protein to the ER.

• The deletion removes a glycosylation site, so the protein cannot be properly glycosylated.

• Phenylalanine 508 is part of the active site that binds chloride, so without it the channel can’t function.

• Without phenylalanine 508, the protein cannot be translated by the ribosome.

The deletion disrupts protein folding. The ER quality control system recognizes the misfolded protein and targets it for degradation before it can reach the cell surface.

The sweat chloride test is the gold standard diagnostic test for cystic fibrosis. In normal sweat glands, CFTR on the surface of sweat duct cells reabsorbs Cl⁻ from the sweat as it travels toward the skin surface. In CF patients, sweat chloride is elevated (Ethan: 78 mEq/L; normal: < 30 mEq/L). Which of the following best explains why?

• Without CFTR in the sweat duct membrane, Cl⁻ cannot be reabsorbed from the sweat, so it remains in the sweat and is excreted at high concentrations.

• CF patients produce more chloride in their sweat glands due to increased cellular metabolism.

• Without CFTR, sodium channels become overactive and pull chloride into the sweat passively.

• The ΔF508 mutation causes CFTR to pump extra chloride into the sweat.

• Elevated sweat chloride is caused by bacterial infections in the sweat glands.

Without CFTR in the sweat duct membrane, Cl⁻ cannot be reabsorbed from the sweat, so it remains in the sweat and is excreted at high concentrations.

During DNA replication, the region ahead of the replication fork accumulates positive supercoils. Which of the following best describes the function of topoisomerases in resolving this problem? 

• They permanently remove supercoils by degrading the overwound DNA segment.

• They unwind the double helix by breaking hydrogen bonds between base pairs.

• They cut one or both DNA strands, allow the helix to relax, and then reseal the break, changing the linking number of the DNA.

• They synthesize new DNA ahead of the fork to replace the overwound region.

• They add methyl groups to the DNA backbone to relieve torsional strain.

They cut one or both DNA strands, allow the helix to relax, and then reseal the break, changing the linking number of the DNA.

During catalysis, topoisomerase II forms a transient covalent bond with the DNA it has cut. What is the chemical nature of this bond? 

• A disulfide bond between a cysteine on the enzyme and a thiol group on the DNA.

• An ionic bond between a lysine on the enzyme and the phosphate backbone.

• A hydrogen bond between the enzyme and the DNA bases.

• A phosphotyrosine bond between a tyrosine residue on the enzyme and the 5′-phosphate of the cut DNA strand.

• A glycosidic bond between the enzyme and a deoxyribose sugar on the DNA.

A phosphotyrosine bond between a tyrosine residue on the enzyme and the 5′-phosphate of the cut DNA strand.

Etoposide is classified as a topoisomerase II “poison” rather than a topoisomerase II “inhibitor.” Which of the following best explains this distinction? 

• Etoposide denatures topoisomerase II, irreversibly destroying the enzyme.

• Etoposide blocks the active site of topoisomerase II and prevents it from binding DNA, like a competitive inhibitor.

• Etoposide is toxic to the patient, whereas inhibitors are not.

• Etoposide allows topoisomerase II to cut the DNA normally but prevents it from resealing the break, trapping the enzyme as a covalent complex on the broken DNA.

• Etoposide binds to DNA directly and prevents topoisomerase II from recognizing its substrate.

Etoposide allows topoisomerase II to cut the DNA normally but prevents it from resealing the break, trapping the enzyme as a covalent complex on the broken DNA.

Etoposide kills both Mr. Torres’s cancer cells and his bone marrow cells, but does not significantly damage his neurons or skeletal muscle cells. Which of the following best explains why? 

• Cancer cells and bone marrow cells are rapidly dividing, requiring high levels of topoisomerase activity. This creates more cleavage complexes that etoposide can trap. Quiescent cells have minimal topoisomerase activity.

• Neurons and muscle cells do not contain topoisomerase II.

• Etoposide can only enter cells that are in the S phase of the cell cycle, and only cancer cells are in S phase.

• Cancer cells and bone marrow cells have a different isoform of topoisomerase II that is more sensitive to etoposide.

• Neurons and muscle cells have drug efflux pumps that remove etoposide before it can act.

Cancer cells and bone marrow cells are rapidly dividing, requiring high levels of topoisomerase activity. This creates more cleavage complexes that etoposide can trap. Quiescent cells have minimal topoisomerase activity.