Signal transduction pathways Practice Questions

Q: A 6-week-old infant presents with vomiting, jaundice, hepatomegaly, and cataracts. Urine reducing substances are positive, but glucose oxidase strip is negative. The infant is being breastfed. Red blood cell galactose-1-phosphate levels are markedly elevated. Based on the biochemical findings, which enzyme is most likely deficient?

Galactose-1-phosphate uridylyltransferase. ***Galactose-1-phosphate uridylyltransferase*** - Deficiency in this enzyme (GALT) leads to **Classic Galactosemia**, characterized by the accumulation of **galactose-1-phosphate**, which is toxic to the liver, kidneys, and brain. - Clinical presentation includes **jaundice**, **hepatomegaly**, and **vomiting** shortly after starting breast milk, along with positive **urine reducing substances** (galactose) and **cataracts**. *Galactokinase* - A deficiency in **galactokinase (GALK)** leads to the accumulation of **galactitol**, which causes isolated **cataracts** without systemic illness. - Unlike GALT deficiency, there is no accumulation of **galactose-1-phosphate**, so patients do not present with **liver failure** or **jaundice**. *UDP-glucose-4-epimerase* - This rare form of galactosemia can present similarly to the classic form but is usually distinguished by specific **isoenzyme** involvement. - While it can cause systemic symptoms, the **biochemical hallmark** in this clinical context specifically highlights the accumulation of **galactose-1-phosphate**, which directly points to GALT deficiency. *Phenylalanine hydroxylase* - Deficiency in this enzyme causes **Phenylketonuria (PKU)**, which presents with intellectual disability and a **mousy odor**, not acute neonatal liver failure. - PKU does not result in positive **urine reducing substances** or the formation of **cataracts** in early infancy. *Homogentisate oxidase* - This enzyme deficiency causes **Alkaptonuria**, a condition characterized by urine that turns black upon standing due to **homogentisic acid**. - It typically presents in adulthood with **ochronosis** and arthritis, rather than acute neonatal **vomiting** or **hepatomegaly**.

Question 1

A 6-week-old infant presents with vomiting, jaundice, hepatomegaly, and cataracts. Urine reducing substances are positive, but glucose oxidase strip is negative. The infant is being breastfed. Red blood cell galactose-1-phosphate levels are markedly elevated. Based on the biochemical findings, which enzyme is most likely deficient?

Accepted Answer

Galactose-1-phosphate uridylyltransferase

Answer

Galactokinase

Answer

UDP-glucose-4-epimerase

Answer

Phenylalanine hydroxylase

Answer

Homogentisate oxidase

Question 2

A research team discovers a novel bacterial toxin that causes severe hypotension in infected patients. In vitro studies show the toxin ADP-ribosylates a specific amino acid on Gq alpha subunits, preventing their activation by GPCRs. Patients develop hypotension despite elevated levels of vasopressin, angiotensin II, and endothelin-1. Synthesize the pathophysiological mechanism explaining why multiple vasopressor hormones fail to maintain blood pressure in these patients.

Accepted Answer

ADP-ribosylation of Gq prevents PLC activation, blocking IP3-mediated calcium release and vascular smooth muscle contraction

Answer

The toxin depletes intracellular ATP preventing myosin-actin interaction

Answer

The toxin prevents receptor binding of vasopressor hormones through allosteric inhibition

Answer

ADP-ribosylation increases cAMP levels causing smooth muscle relaxation

Answer

The toxin activates Gi proteins causing excessive vasodilation that overwhelms vasoconstrictor signals

Question 3

A 42-year-old woman with metastatic melanoma develops severe colitis while being treated with ipilimumab (anti-CTLA-4 antibody) and nivolumab (anti-PD-1 antibody). Her oncologist must decide whether to continue immunotherapy or treat the colitis with immunosuppression. Tumor analysis shows high PD-L1 expression and BRAF wild-type status. Previous conventional chemotherapy failed. Evaluate the optimal management strategy considering signal transduction implications.

Accepted Answer

Discontinue ipilimumab, continue nivolumab with corticosteroids, as PD-1 pathway blockade may be sufficient given high PD-L1 expression

Answer

Stop both drugs permanently as immune-related adverse events indicate loss of self-tolerance mechanisms

Answer

Continue both checkpoint inhibitors as tumor response depends on sustained T-cell receptor co-stimulation blockade

Answer

Continue both drugs but add TNF-alpha inhibitor to block inflammatory signaling without affecting anti-tumor immunity

Answer

Stop all immunotherapy and switch to targeted therapy despite BRAF wild-type status

Question 4

A 35-year-old man with familial adenomatous polyposis (FAP) undergoes genetic counseling. He has a germline APC mutation and asks about cancer risk for his children. His physician explains that APC normally regulates beta-catenin levels. Evaluate which downstream transcriptional consequence most directly results from loss of functional APC protein in colonic epithelial cells.

Accepted Answer

Constitutive TCF/LEF-mediated transcription of proliferation genes due to nuclear beta-catenin accumulation

Answer

Increased SMAD-mediated transcription of growth inhibitory genes

Answer

Decreased TCF/LEF-mediated transcription of cell cycle genes like c-MYC and cyclin D1

Answer

Increased p53-mediated transcription of pro-apoptotic genes

Answer

Decreased NF-kB transcriptional activity reducing inflammatory gene expression

Question 5

A 58-year-old woman with HER2-positive metastatic breast cancer initially responds to trastuzumab (anti-HER2 antibody) but develops resistance after 18 months. Tumor analysis reveals increased expression of HER3 and continued PI3K/AKT pathway activation despite HER2 blockade. Analyze the mechanism underlying this adaptive resistance.

Accepted Answer

HER3 directly activates PI3K independent of HER2 through compensatory heterodimerization with other receptors

Answer

HER3 activates p53 pathway bypassing the need for HER2 signaling

Answer

HER3 increases expression of drug efflux pumps removing trastuzumab from cells

Answer

HER3 downregulates HER2 expression eliminating the drug target

Answer

HER3 blocks trastuzumab binding sites on HER2 through steric hindrance

Signal transduction pathways — MCQs

Signal transduction pathways — MCQs

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