A 28-year-old woman of Mediterranean descent presents with acute hemolytic anemia after ingesting fava beans. Her blood smear shows bite cells and Heinz bodies. Regarding the pentose phosphate pathway in this clinical context, all of the following are true EXCEPT:

Question

Accepted Answer

C. The non-oxidative phase of the PPP can be bypassed entirely without affecting NADPH production, as NADPH is generated solely in the oxidative phase. ## G6PD Deficiency & Pentose Phosphate Pathway — Clinical Correlation ### Clinical Context: Favism **Key Point:** This is a classic presentation of **glucose-6-phosphate dehydrogenase (G6PD) deficiency**, the most common enzyme deficiency worldwide, affecting ~400 million people, particularly in Mediterranean, African, and Asian populations. **Clinical Pearl:** Fava beans contain oxidative stressors (divicine, isouramil) that trigger hemolysis in G6PD-deficient individuals. Bite cells (RBCs with a "bite" taken out by the spleen) and Heinz bodies (denatured hemoglobin precipitates) are pathognomonic findings. ### Why Option 0 is Incorrect The statement claims: "The non-oxidative phase of the PPP can be bypassed entirely without affecting NADPH production." This is **fundamentally wrong** because: 1. **NADPH is generated ONLY in the oxidative phase** — specifically by two reactions: - Glucose-6-phosphate → 6-phosphogluconolactone (catalyzed by G6PD) - 6-phosphogluconate → ribulose-5-phosphate (catalyzed by 6-phosphogluconate dehydrogenase) 2. **The non-oxidative phase does NOT generate NADPH** — it is purely a carbon-rearrangement phase that produces pentose sugars (ribose-5-phosphate for nucleotide synthesis) and glycolytic intermediates 3. **However**, the non-oxidative phase is NOT "bypassable" without consequence: - If the non-oxidative phase is blocked, ribulose-5-phosphate accumulates - This feedback-inhibits the oxidative phase, reducing NADPH production - The pathway is designed so that the ratio of oxidative-to-non-oxidative flux depends on cellular demand for NADPH vs. ribose-5-phosphate **High-Yield:** In G6PD deficiency, the already-compromised oxidative phase cannot generate sufficient NADPH. The non-oxidative phase cannot compensate because it produces zero NADPH. This is why RBCs are uniquely vulnerable — they depend entirely on PPP for NADPH and cannot use alternative pathways (no mitochondria, no other NADPH-generating systems). ### Verification of Other Options | Statement | Correct? | Mechanism | |-----------|----------|----------| | G6PD deficiency impairs GSH regeneration | ✓ Yes | NADPH + H^+^ + GSSG → 2 GSH (via glutathione reductase). Without NADPH, GSH cannot be reduced, and antioxidant capacity collapses | | Fava bean oxidants trigger hemolysis in G6PD-deficient RBCs | ✓ Yes | Oxidative stress overwhelms the already-deficient antioxidant system; RBCs cannot maintain membrane integrity and lyse | | PPP is the only NADPH source in mature RBCs | ✓ Yes | Mature RBCs lack mitochondria and cannot use the TCA cycle or other NADPH-generating pathways; they are entirely dependent on PPP | **Mnemonic — G6PD Hemolysis Cascade:** **"FADING"** = **F**ava beans → **A**ntioxidant collapse → **D**amage to RBC membrane → **I**ntravascular hemolysis → **N**eed for transfusion → **G**6PD deficiency confirmed. ```mermaid flowchart TD A[Fava bean ingestion
divicine, isouramil]:::action --> B[Oxidative stress
ROS generation]:::outcome B --> C{G6PD present?}:::decision C -->|Yes| D[G6PD generates NADPH
Oxidative phase active]:::action C -->|No| E[G6PD deficient
Minimal NADPH]:::urgent D --> F[Glutathione reductase
regenerates GSH]:::action E --> G[GSH cannot be reduced
Antioxidant defense fails]:::urgent F --> H[RBCs protected
No hemolysis]:::outcome G --> I[ROS accumulates
Hemoglobin denaturation]:::urgent I --> J[Bite cells, Heinz bodies
Hemolytic anemia]:::outcome ```

Answer

A. Glucose-6-phosphate dehydrogenase deficiency impairs the regeneration of reduced glutathione (GSH), compromising the antioxidant defense system

Answer

B. The pentose phosphate pathway is the only source of NADPH in mature red blood cells, making them particularly vulnerable to oxidative damage when G6PD is deficient

Answer

D. Oxidative stress from fava bean metabolites (divicine and isouramil) triggers hemolysis in G6PD-deficient RBCs because they cannot maintain adequate GSH levels

A 28-year-old woman of Mediterranean descent presents with acute hemolytic anemia after ingesting fava beans. Her blood smear shows bite cells and Heinz bodies. Regarding the pentose phosphate pathway in this clinical context, all of the following are true EXCEPT:

Explanation

G6PD Deficiency & Pentose Phosphate Pathway — Clinical Correlation

Clinical Context: Favism

Why Option 0 is Incorrect

Verification of Other Options

Practice similar questions

Join our NEET PG community

Statement	Correct?	Mechanism
G6PD deficiency impairs GSH regeneration	✓ Yes	NADPH + H⁺ + GSSG → 2 GSH (via glutathione reductase). Without NADPH, GSH cannot be reduced, and antioxidant capacity collapses
Fava bean oxidants trigger hemolysis in G6PD-deficient RBCs	✓ Yes	Oxidative stress overwhelms the already-deficient antioxidant system; RBCs cannot maintain membrane integrity and lyse
PPP is the only NADPH source in mature RBCs	✓ Yes	Mature RBCs lack mitochondria and cannot use the TCA cycle or other NADPH-generating pathways; they are entirely dependent on PPP