An alcoholic patient presents with confusion, ophthalmoplegia and ataxia. Erythrocyte transketolase activity is reduced and shows a large increase after addition of thiamine pyrophosphate in vitro. Transketolase requires its cofactor TPP because TPP:

• A Provides a sulfhydryl group for disulfide exchange at the active site
• B Stabilises the carbanion formed on a hydroxyethyl group during transfer of two-carbon fragments ✓
• C Donates hydride equivalents through its isoalloxazine ring
• D Carries activated one-carbon units as formiminoglutamate

Explanation

Thiamine pyrophosphate contains a reactive thiazolium ring whose acidic carbon forms a carbanion (ylide). This attacks carbonyl carbons and stabilises the negatively charged hydroxyethyl intermediate, allowing decarboxylation of alpha-keto acids and transfer of two-carbon glycolaldehyde units by transketolase. The isoalloxazine ring described in option C belongs to FAD, while one-carbon carriers such as tetrahydrofolate handle formimino groups.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.