Thiamine pyrophosphate (TPP) is the active form of thiamine. In severe thiamine deficiency (Wernicke's encephalopathy), which enzymes are primarily affected, explaining the clinical presentation?

• A Pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase ✓
• B Glutamate dehydrogenase and NADH dehydrogenase
• C Pyruvate carboxylase and acetyl-CoA carboxylase
• D Succinate dehydrogenase and fumarase

Explanation

Thiamine pyrophosphate (TPP) is the cofactor for three key decarboxylases: (1) pyruvate dehydrogenase (PDH) — pyruvate → acetyl-CoA; (2) alpha-ketoglutarate dehydrogenase (KGDH) — alpha-KG → succinyl-CoA in TCA cycle; (3) transketolase — reactions in the pentose phosphate pathway (HMP shunt). In thiamine deficiency, reduced PDH activity causes pyruvate/lactate accumulation (lactic acidosis), reduced KGDH impairs TCA cycle and ATP production in neural tissue (particularly cerebellum, medial thalami, mamillary bodies — vulnerable due to high metabolic demand), and transketolase impairment reduces NADPH and nucleotide synthesis. Red cell transketolase activity is the most sensitive laboratory test for thiamine deficiency.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.