Molecular Physiology Practice Questions

Q: A 45-year-old woman with breast cancer is being treated with trastuzumab (Herceptin). Laboratory analysis of her tumor cells shows 100-fold amplification of a specific gene. Analysis of the signal transduction pathway reveals constitutive activation of PI3K/AKT pathway. Which receptor is most likely overexpressed?

Human epidermal growth factor receptor 2 (HER2). ***Human epidermal growth factor receptor 2 (HER2)*** - **Trastuzumab** is a monoclonal antibody specifically designed to target the **HER2/neu (ERBB2)** receptor, which is overexpressed in approximately 20-30% of breast cancers. - **HER2** is a receptor tyrosine kinase that, when amplified, leads to constitutive activation of the **PI3K/AKT** and **MAPK** pathways, driving uncontrolled cell proliferation. *Vascular endothelial growth factor receptor (VEGFR)* - **VEGFR** is primarily involved in **angiogenesis** (the formation of new blood vessels) and is the target of drugs like **bevacizumab**, not trastuzumab. - While important in many cancers, its signaling pathway is not the primary target in the standard clinical use of trastuzumab for breast cancer. *Progesterone receptor (PR)* - **PR** is a **nuclear receptor** that functions as a transcription factor, not a cell surface receptor tyrosine kinase that activates the **PI3K/AKT** pathway directly. - Overexpression of PR is managed with **hormonal therapies** (like aromatase inhibitors), but it is not the target of the antibody **trastuzumab**. *Estrogen receptor (ER)* - Similar to the progesterone receptor, the **ER** is an intracellular receptor used to guide treatment with drugs like **Tamoxifen**. - Genes for ER are not typically subject to the **100-fold amplification** described, as ER status is usually determined by ligand-dependent signaling rather than massive gene duplication.

Q: Which of the following is not a channelopathy?

Tay-sach's disease. **Explanation:** **Channelopathies** are a group of disorders caused by mutations in genes encoding ion channel proteins or their regulatory subunits, leading to dysfunctional ion transport across cell membranes. **Why Tay-Sachs Disease is the Correct Answer:** Tay-Sachs disease is **not** a channelopathy; it is a **Lysosomal Storage Disorder**. It is caused by a deficiency of the enzyme **Hexosaminidase A**, leading to the toxic accumulation of GM2 gangliosides in neurons. Clinically, it presents with neurodegeneration, developmental delay, and a characteristic **cherry-red spot** on the macula. **Analysis of Incorrect Options:** * **Cystic Fibrosis:** This is a classic channelopathy caused by mutations in the **CFTR gene**, which encodes a cAMP-regulated **Chloride channel**. Dysfunction leads to thick, viscid secretions in the lungs and pancreas. * **Liddle’s Syndrome:** A genetic form of hypertension caused by a "gain-of-function" mutation in the **ENaC (Epithelial Sodium Channel)** in the collecting ducts of the kidney, leading to excessive sodium reabsorption. * **Hypokalemic Periodic Paralysis:** A skeletal muscle channelopathy most commonly involving the **voltage-gated Calcium channel (Cav1.1)** or Sodium channel (Nav1.4), resulting in episodes of muscle weakness triggered by low serum potassium. **High-Yield Clinical Pearls for NEET-PG:** * **Common Channelopathies to Remember:** Lambert-Eaton Syndrome (Ca²⁺ channel), Myasthenia Gravis (ACh-gated Na⁺ channel), and Long QT Syndrome (K⁺/Na⁺ channels). * **Bartter’s and Gitelman’s Syndromes** are also important renal channelopathies involving salt transporters. * **Tay-Sachs Mnemonic:** "A **Gang** of **Six** (**Hex**osaminidase) **Small** (**Tay**-Sachs) **Cherries** (Cherry-red spot)."

Q: What is the composition of epithelial sodium channels?

1α, 1β, 1γ. ***1α, 1β, 1γ*** - Epithelial sodium channels (**ENaCs**) are heterotrimeric complexes composed of one **alpha (α)**, one **beta (β)**, and one **gamma (γ) subunit**. - This specific subunit composition is essential for the channel's proper function in **sodium reabsorption** across epithelial tissues. *2α, 1β* - This composition is incomplete as it lacks the **gamma (γ) subunit**, which is a crucial component of the functional ENaC. - While alpha and beta subunits are present, the absence of the gamma subunit would impair the channel's ability to efficiently transport sodium. *2α, 1β, 2γ* - This composition is incorrect because a functional ENaC typically includes only **one gamma (γ) subunit**, not two. - An imbalance in subunit stoichiometry can lead to misfolding or improper assembly, affecting channel function. *2α, 1β, 1γ* - This combination correctly includes all three types of subunits (alpha, beta, gamma) but incorrectly states there are **two alpha (α) subunits**. - A functional ENaC has a single alpha subunit, making this option incorrect.

Question 1

A novel drug is designed to treat a genetic disorder caused by a nonsense mutation in the dystrophin gene. The drug works by allowing the ribosome to skip over the premature stop codon and continue translation. Evaluation of this therapeutic strategy reveals partial restoration of dystrophin protein with 60% of normal length but sufficient function. What is the most critical molecular consideration in determining if this approach will be clinically beneficial?

Accepted Answer

Whether the truncated protein retains the actin-binding domain and maintains membrane stability

Answer

Whether the drug prevents degradation of dystrophin mRNA

Answer

Whether the drug enhances ribosomal binding to the start codon

Answer

Whether the drug increases transcription of the dystrophin gene

Question 2

A 45-year-old woman with breast cancer is being treated with trastuzumab (Herceptin). Laboratory analysis of her tumor cells shows 100-fold amplification of a specific gene. Analysis of the signal transduction pathway reveals constitutive activation of PI3K/AKT pathway. Which receptor is most likely overexpressed?

Accepted Answer

Human epidermal growth factor receptor 2 (HER2)

Answer

Vascular endothelial growth factor receptor (VEGFR)

Answer

Progesterone receptor (PR)

Answer

Estrogen receptor (ER)

Question 3

A 6-month-old infant presents with severe anemia, jaundice, and hepatosplenomegaly. Hemoglobin electrophoresis shows predominantly HbF (fetal hemoglobin) with absent HbA. Which molecular defect best explains this clinical picture?

Accepted Answer

Deletion or mutation in beta-globin gene causing beta-thalassemia major

Answer

Deletion in alpha-globin gene causing alpha-thalassemia

Answer

Point mutation in beta-globin gene causing sickle cell disease

Answer

Mutation in gamma-globin gene

Question 4

Which of the following is not a channelopathy?

Accepted Answer

Tay-sach's disease

Answer

Cystic fibrosis

Answer

Liddle's syndrome

Answer

Hypokalemic periodic paralysis

Question 5

What is the composition of epithelial sodium channels?

Accepted Answer

1α, 1β, 1γ

Answer

2α, 1β, 1γ

Answer

2α, 1β

Answer

2α, 1β, 2γ

Molecular Physiology — MCQs

Molecular Physiology — MCQs

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