In the HMP shunt (pentose phosphate pathway), the non-oxidative phase is catalyzed by transketolase and transaldolase. A patient with chronic alcoholism and thiamine deficiency would show impaired activity of transketolase because thiamine pyrophosphate (TPP) is an essential cofactor. Which ADDITIONAL TPP-dependent enzyme would be simultaneously impaired, contributing to neurological symptoms?

• A Phosphogluconate dehydrogenase
• B Glucose-6-phosphate dehydrogenase
• C Phosphofructokinase-1
• D Alpha-ketoglutarate dehydrogenase ✓

Explanation

Thiamine pyrophosphate (TPP) is required by three key mitochondrial enzyme complexes: pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase (in the TCA cycle), and branched-chain alpha-keto acid dehydrogenase — as well as transketolase in the cytoplasm. Impairment of alpha-ketoglutarate dehydrogenase reduces TCA cycle flux, impairing neuronal ATP production and contributing to the neurological manifestations of Wernicke's encephalopathy. Glucose-6-phosphate dehydrogenase and phosphogluconate dehydrogenase use NADP+, not TPP.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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