Cell Structure
A 23-year-old woman with systemic lupus erythematosus is started on hydroxychloroquine. The drug is a weak base with a pKa of 8.5 and is found to accumulate within acidic intracellular organelles. Which of the following best explains the intracellular accumulation of this drug?
A. Active transport of the drug against its concentration gradient
B. Covalent binding of the drug to lysosomal proteins
C. Conversion of the drug to a more lipid-soluble form in acidic environments
D. Protonation of the drug within acidic compartments, preventing membrane diffusion
E. Transport of the drug through voltage-gated ion channels
D. Protonation of the drug within acidic compartments, preventing membrane diffusion
Once inside acidic organelles such as lysosomes, it becomes protonated and positively charged. The charged form cannot readily cross the lipid membrane, causing the drug to become trapped within the organelle (ion trapping). This increases lysosomal pH and can impair lysosomal function.
A 17-year-old man presents with a history of recurrent sinusitis, chronic productive cough, and infertility. CT of the chest demonstrates bronchiectasis, and imaging reveals situs inversus. Electron microscopy of respiratory epithelial cells shows abnormal ciliary movement.
Which of the following cellular structures is most likely dysfunctional?
A. Actin microfilaments
B. Intermediate filaments
C. Microtubules
D. Myosin thick filaments
E. Spectrin
C. Microtubules
Cilia are composed of microtubules arranged in a 9 + 2 pattern. Their movement is generated by dynein, which causes sliding between adjacent microtubules. Kartagener syndrome is classically associated with dynein arm defects.
A mutation replaces several glycine residues in a protein with bulky amino acids. The resulting protein demonstrates reduced flexibility and abnormal folding.
Which property of glycine normally contributes to protein flexibility?
A. Positively charged side chain
B. Negatively charged side chain
C. Aromatic ring
D. Minimal side-chain steric hindrance
E. Ability to form disulfide bonds
D. Minimal side-chain steric hindrance
Glycine has a hydrogen atom as its side chain, making it the smallest amino acid. It provides increased flexibility to the polypeptide backbone
A 6-month-old infant is brought to the pediatrician for developmental delay, seizures, and eczema. The infant has a musty body odor and unusually light skin and hair. Laboratory studies reveal markedly elevated phenylalanine levels.
Which of the following amino acids is most likely deficient in this patient?
A. Tyrosine
B. Tryptophan
C. Methionine
D. Histidine
E. Glutamine
A. Tyrosine
Phenylketonuria is caused by phenylalanine hydroxylase deficiency or tetrahydrobiopterin deficiency. Phenylalanine cannot be converted to tyrosine, making tyrosine an essential amino acid in PKU.
Two enzymes catalyze the same reaction in different tissues. Enzyme A has a Km of 1 μM, while enzyme B has a Km of 100 μM.
Which of the following best describes enzyme A?
A. Lower affinity for the substrate
B. Higher affinity for the substrate
C. Higher Vmax
D. Lower Vmax
E. Greater activation energy
B. Higher affinity for the substrate
Km is inversely related to enzyme affinity for its substrate. A lower Km means that a lower substrate concentration is required to achieve half of Vmax, indicating higher substrate affinity.
A 20-year-old man has a mutation that disrupts the ability of certain cell-surface receptors to cluster within cholesterol-rich regions of the plasma membrane. As a result, downstream signaling following receptor activation is significantly reduced.
Which of the following membrane structures is most likely affected?
A. Lysosomes
B. Lipid rafts
C. Peroxisomes
D. Nuclear pores
E. Ribosomes
B. Lipid rafts
Lipid rafts organize receptors and signaling proteins into specialized membrane microdomains. Disruption of these domains can interfere with efficient signal transduction.
A 23-year-old woman develops recurrent blistering of the skin after minor trauma. Genetic testing reveals a mutation affecting a protein that provides mechanical strength to epidermal cells. Microscopic examination demonstrates disruption of the cytoskeletal network that normally connects the cell membrane to the nucleus.
Which of the following cytoskeletal components is most likely affected?
A. Actin microfilaments
B. Intermediate filaments
C. Microtubules
D. Dynein
E. Myosin
B. Intermediate filaments
Keratin is an intermediate filament found in epithelial cells. Mutations in keratin genes can cause epidermolysis bullosa simplex, in which epidermal cells become fragile and rupture with mechanical stress.
A 2-week-old infant develops poor feeding, vomiting, lethargy, and intermittent muscle rigidity. The infant's urine has a characteristic sweet, maple syrup-like odor. Laboratory testing reveals elevated branched-chain amino acids.
Which of the following amino acids is most likely elevated?
A. Alanine
B. Leucine
C. Glycine
D. Tyrosine
E. Glutamate
B. Leucine
Maple syrup urine disease results from deficiency of branched-chain α-ketoacid dehydrogenase, leading to accumulation of leucine, isoleucine, and valine
A 42-year-old man presents with darkening of the sclera and chronic lower back pain. His urine turns dark after standing. Genetic testing reveals a deficiency in an enzyme involved in tyrosine degradation.
Which of the following substances is most likely to accumulate?
A. Phenylalanine
B. Tyrosine
C. Homogentisic acid
D. Melanin
E. DOPA
C. Homogentisic acid
Alkaptonuria is caused by deficiency of homogentisate oxidase, resulting in accumulation of homogentisic acid.
A researcher measures the kinetics of an enzyme-catalyzed reaction. The concentration of substrate is maintained at a very high level. The researcher then doubles the concentration of enzyme.
Which of the following changes is most likely?
A. Km increases
B. Km decreases
C. Vmax increases
D. Vmax decreases
E. ΔG increases
C. Vmax increases
Increasing enzyme concentration increases the number of available active sites and therefore increases the maximum reaction velocity (Vmax). The enzyme's affinity for its substrate does not change, so Km remains unchanged
A researcher genetically modifies a fungal species so that it produces cholesterol instead of ergosterol in its plasma membrane. The modified fungus is then exposed to nystatin.
Which of the following is most likely to occur?
A. Increased susceptibility to nystatin
B. Decreased susceptibility to nystatin
C. No change in susceptibility
D. Increased inhibition of fungal DNA synthesis
E. Increased inhibition of fungal cell wall synthesis
B. Decreased susceptibility to nystatin
Nystatin preferentially binds ergosterol. Replacing ergosterol with cholesterol would reduce the drug's ability to interact with the fungal membrane and form pores, resulting in decreased susceptibility.
A 58-year-old woman with metastatic breast cancer is treated with paclitaxel. The medication binds to tubulin and prevents microtubule depolymerization.
Which cellular process is most directly disrupted?
A. DNA replication
B. Formation of the mitotic spindle
C. Actin-mediated muscle contraction
D. Intermediate filament assembly
E. Ribosomal RNA synthesis
B. Formation of the mitotic spindle
Microtubules must undergo dynamic polymerization and depolymerization during mitosis. Paclitaxel stabilizes microtubules and prevents their depolymerization, disrupting the mitotic spindle and causing cell-cycle arrest
A 24-year-old man presents with recurrent episodes of severe bone pain and anemia. Genetic analysis reveals a point mutation in the β-globin gene that results in substitution of valine for glutamate at the sixth amino acid position.
Which of the following best explains how this mutation contributes to disease?
A. Increased formation of disulfide bonds
B. Increased hydrophobic interactions between hemoglobin molecules
C. Disruption of peptide bonds in hemoglobin
D. Decreased α-helical content due to proline substitution
E. Increased solubility of deoxygenated hemoglobin
B. Increased hydrophobic interactions between hemoglobin molecules
In sickle cell disease, glutamate (polar and hydrophilic) is replaced by valine (nonpolar and hydrophobic). This creates a hydrophobic region on the surface of deoxygenated hemoglobin, promoting intermolecular aggregation and polymerization, leading to sickling.
A 2-year-old child has very light skin and hair and develops severe sun sensitivity. Laboratory testing demonstrates normal phenylalanine and tyrosine concentrations. A genetic mutation affects an enzyme involved in melanin production.
Which of the following enzymes is most likely defective?
A. Phenylalanine hydroxylase
B. Tyrosinase
C. Homogentisate oxidase
D. Tyrosine hydroxylase
E. DOPA decarboxylase
B. Tyrosinase
Tyrosinase catalyzes the rate-limiting steps in melanin synthesis:
A 42-year-old man with gout is treated with a medication that inhibits xanthine oxidase, thereby decreasing uric acid production. The drug competes with the enzyme's substrate for binding to the active site.
Which of the following changes in enzyme kinetics is most likely to occur in the presence of this medication?
A. Decreased Km and decreased Vmax
B. Decreased Km and unchanged Vmax
C. Increased Km and unchanged Vmax
D. Unchanged Km and decreased Vmax
E. Increased Km and decreased Vmax
C. Increased Km and unchanged Vmax
A competitive inhibitor competes with substrate for the active site. Increasing substrate concentration can overcome the inhibition, so Vmax remains unchanged. However, more substrate is required to reach half of Vmax, resulting in an increased Km.
A 40-year-old man consumes ethanol. In hepatocytes, the first step in ethanol metabolism is catalyzed by alcohol dehydrogenase. A mutation causes this enzyme to be absent from the cytosol.
Which of the following reactions would be most directly impaired?
A. Ethanol → Acetaldehyde
B. Acetaldehyde → Acetate
C. Acetate → Acetyl-CoA
D. Acetyl-CoA → CO₂
E. Pyruvate → Lactate
A. Ethanol → Acetaldehyde
Alcohol dehydrogenase catalyzes the conversion of ethanol to acetaldehyde in the cytosol. The next step, conversion of acetaldehyde to acetate, occurs primarily in the mitochondria and is catalyzed by aldehyde dehydrogenase
A 51-year-old man presents with acute pain, erythema, and swelling of the first metatarsophalangeal joint. Synovial fluid analysis reveals needle-shaped, negatively birefringent crystals. He is treated with colchicine.
Which of the following best describes the mechanism of action of this medication?
A. Inhibition of actin polymerization
B. Inhibition of tubulin polymerization
C. Stabilization of microtubules
D. Inhibition of myosin ATPase
E. Disruption of intermediate filaments
B. Inhibition of tubulin polymerization
Colchicine binds tubulin and prevents microtubule polymerization. This inhibits neutrophil chemotaxis and degranulation, reducing inflammation during an acute gout attack.
A mutation occurs in a protein at an amino acid residue located within an α-helix. The mutation causes a major alteration in protein structure and results in a 50% reduction in protein function.
Which of the following amino acid substitutions is most likely to produce the greatest structural disruption?
A. Glutamate → Aspartate
B. Serine → Threonine
C. Leucine → Isoleucine
D. Aspartate → Lysine
E. Glycine → Alanine
D. Aspartate → Lysine
Aspartate is negatively charged, whereas lysine is positively charged at physiologic pH. This is a nonconservative substitution that can disrupt ionic interactions and protein folding.
A 29-year-old woman is being evaluated for a disorder affecting neurotransmitter synthesis. A researcher studies the biosynthetic pathway of catecholamines.
Which of the following is the correct sequence?
A. Tyrosine → Dopamine → DOPA → Epinephrine → Norepinephrine
B. Phenylalanine → DOPA → Tyrosine → Dopamine → Epinephrine
C. A. Tyrosine → DOPA → Dopamine → Norepinephrine → Epinephrine
D. Tyrosine → Serotonin → Dopamine → Norepinephrine
E. A. Tyrosine → DOPA → Dopamine → Epinephrine → Norepinephrine
C. A. Tyrosine → DOPA → Dopamine → Norepinephrine → Epinephrine
A metabolic enzyme is inhibited by the final product of a biochemical pathway. When the concentration of the final product increases, the activity of the first enzyme in the pathway decreases.
Which of the following best describes this regulatory mechanism?
A. Competitive inhibition
B. Feedback inhibition
C. Irreversible inhibition
D. Substrate induction
E. Covalent degradation
B. Feedback inhibition
In feedback inhibition, the final product of a metabolic pathway inhibits an enzyme involved in an earlier step, preventing excessive accumulation of the pathway's products
A 38-year-old man taking disulfiram accidentally consumes several alcoholic drinks. Shortly afterward, he develops facial flushing, headache, nausea, vomiting, and tachycardia.
Which of the following substances is most directly responsible for these symptoms?
A. Ethanol
B. Acetaldehyde
C. Acetate
D. Acetyl-CoA
E. Lactate
B. Acetaldehyde
Disulfiram inhibits aldehyde dehydrogenase, causing accumulation of acetaldehyde, which produces the unpleasant symptoms of the disulfiram-alcohol reaction
A 30-year-old woman presents with fluctuating muscle weakness that worsens throughout the day. She has ptosis and diplopia that improve with rest. Antibodies against postsynaptic acetylcholine receptors are detected.
The skeletal muscle contraction that produces her symptoms ultimately depends on interaction between which cytoskeletal proteins?
A. Actin and myosin
B. Tubulin and dynein
C. Keratin and desmin
D. Spectrin and ankyrin
E. Kinesin and dynein
A. Actin and myosin
Skeletal muscle contraction occurs through myosin interacting with actin, causing sliding of thin filaments past thick filaments. Myasthenia gravis disrupts neuromuscular transmission upstream of this process.
A researcher examines the amino acid sequence of a membrane protein and wants to identify a segment that is likely to span the lipid bilayer.
Which of the following sequences is most likely to be located within a transmembrane domain?
A. Asp-Val-Leu-Thr-Glu-Lys-Glu-Ile
B. Glu-Glu-Thr-Glu-Glu-Glu-Val-Gln
C. Ile-Phe-Val-Leu-Ile-Trp-Cys-Leu
D. Lys-Ile-Lys-His-Ser-Arg-Gly-Arg
E. Ser-Thr-Gly-Ala-Gly-Lys-Thr-Ser
C. Ile-Phe-Val-Leu-Ile-Trp-Cys-Leu
The interior of the lipid bilayer is hydrophobic. Therefore, transmembrane regions are enriched in nonpolar amino acids such as leucine, isoleucine, valine, phenylalanine, and tryptophan.
A patient with Chediak-Higashi syndrome has recurrent infections with pyogenic bacteria. Although neutrophils can migrate toward sites of infection, they have impaired intracellular killing of phagocytosed organisms.
Which of the following processes is most likely defective?
A. Formation of immunoglobulins by plasma cells
B. Fusion of phagosomes with lysosomes
C. Complement synthesis by hepatocytes
D. T-cell receptor rearrangement
E. Production of erythropoietin
B. Fusion of phagosomes with lysosomes
After phagocytosis, neutrophils normally destroy pathogens through fusion of the phagosome with lysosomes, forming a phagolysosome. Chediak-Higashi syndrome causes abnormal lysosomal trafficking and impaired phagolysosome formation, reducing microbial killing.
A researcher compares an uncatalyzed biochemical reaction with the same reaction in the presence of an enzyme. The enzyme increases the rate of the reaction without changing the overall free-energy change (ΔG).
Which of the following best explains this effect?
A. The enzyme increases the activation energy
B. The enzyme decreases the activation energy
C. The enzyme increases the equilibrium constant
D. The enzyme shifts the reaction toward the products
E. The enzyme increases the free energy of the products
B. The enzyme decreases the activation energy
Enzymes increase reaction rates by lowering the activation energy (Ea) required to reach the transition state. Enzymes do not change the overall ΔG or equilibrium position of the reaction