Aflatoxin B1, produced by Aspergillus flavus, is converted by hepatic CYP enzymes to the highly reactive 8,9-exo-epoxide that binds DNA. Which Phase II enzyme family provides the principal defence against this epoxide?
- A UDP-glucuronosyltransferases
- B Glutathione S-transferases ✓
- C Sulfotransferases
- D Epoxide hydrolases acting alone
Explanation
The aflatoxin C1 8,9-epoxide is a soft electrophile that is preferentially conjugated with reduced glutathione by glutathione S-transferases, particularly the GSTM1 isoform, forming a mercapturic acid precursor excreted in urine. Individuals with the GSTM1 null genotype show higher aflatoxin-DNA adduct burden and hepatocellular carcinoma risk. Epoxide hydrolase can open the ring but the dominant detoxification route examined is GSH conjugation, which kills option D.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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