All of the following are true regarding the pentose phosphate pathway EXCEPT:

Explanation

## Analysis of Pentose Phosphate Pathway Statements ### Statement 1: G6PD Deficiency & Haemolysis ✓ CORRECT **High-Yield:** G6PD deficiency is the most common enzyme deficiency worldwide (>400 million people). It causes: - **Acute haemolytic crises** triggered by oxidative stress - **Classic triggers:** Fava beans, sulfonamides (TMP-SMX), antimalarials (primaquine), aspirin, NSAIDs - **Mechanism:** Without G6PD → ↓NADPH → ↓reduced glutathione (GSH) → ↓antioxidant defence → RBC haemolysis **Clinical Pearl:** Presents with jaundice, dark urine, splenomegaly 24–72 hours after trigger exposure. ### Statement 2: Pathway Upregulation in Lipogenic Tissues ✓ CORRECT **Key Point:** The PPP is **highly active** in: - **Liver** (cholesterol & fatty acid synthesis) - **Adipose tissue** (triglyceride synthesis) - **Adrenal cortex** (steroid synthesis) - **Lactating mammary gland** (milk fat synthesis) Reason: These tissues have high NADPH demand for reductive biosynthesis. Insulin upregulates G6PD expression in these tissues. ### Statement 3: NADPH & Antioxidant Systems ✓ CORRECT **Key Point:** NADPH is the reducing cofactor for: - **Thioredoxin reductase** (reduces oxidized thioredoxin → active thioredoxin, a universal antioxidant) - **Glutathione reductase** (reduces oxidized glutathione GSSG → reduced GSH, the main cellular antioxidant) - **Catalase and peroxidase** (indirectly, via GSH regeneration) ### Statement 4: Oxidative Phase as Only Route ✗ INCORRECT **High-Yield:** This is the **trap answer**. Glucose-6-phosphate can be converted to ribulose-5-phosphate via **two routes**: ```mermaid flowchart TD A["Glucose-6-phosphate"]:::outcome --> B["Route 1: Oxidative Phase<br/>(G6PD → 6-PG → Ru5P)<br/>Generates 2 NADPH"]:::action A --> C["Route 2: Non-Oxidative Phase<br/>(Glycolysis intermediates<br/>via transketolase/transaldolase)<br/>NO NADPH generated"]:::action B --> D["Ribulose-5-phosphate"]:::outcome C --> D ``` **Mechanism of Route 2:** - Glucose-6-P → Glucose-1-P → UDP-glucose (or enters glycolysis) - Glycolytic intermediates (F6P, G3P) undergo transketolase/transaldolase reactions - These reactions can generate Ru5P **without the oxidative phase** - This occurs especially when NADPH is abundant (inhibiting G6PD) **Clinical Relevance:** In tissues with sufficient NADPH (e.g., well-fed state), cells can bypass the oxidative phase and still generate ribose-5-phosphate via the non-oxidative pathway. ## Summary Statements 1–3 are all correct. Statement 4 falsely claims the oxidative phase is the **only** route; in reality, the non-oxidative phase can independently generate Ru5P from glycolytic intermediates without NADPH production.