Glutathione S-transferase (GST) is a key Phase II detoxification enzyme. In which of the following conditions is the highest expression of hepatic GST desirable, and why?

• A During fasting, because GST conjugates ketone bodies to glycine for renal excretion
• B During haemolysis, because GST recycles oxidised glutathione (GSSG) back to GSH
• C After exposure to polycyclic aromatic hydrocarbons, because GST conjugates their epoxide metabolites (carcinogens) to glutathione for biliary excretion ✓
• D In hyperbilirubinemia, because GST directly conjugates bilirubin to glucuronate for excretion

Explanation

Polycyclic aromatic hydrocarbons (PAHs, e.g., benzo[a]pyrene) are first oxidised by CYP1A1 to reactive epoxide intermediates (arene oxides), which are potent carcinogens that can form DNA adducts. GST catalyses the conjugation of these epoxides with glutathione, forming mercapturic acid conjugates excreted in bile and urine. High hepatic GST expression after PAH exposure is therefore protective. Glutathione reductase (not GST) recycles GSSG to GSH. UDP-glucuronosyltransferase (UGT) conjugates bilirubin.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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