Phase II xenobiotic metabolism involves conjugation reactions that increase hydrophilicity for renal/biliary excretion. Which enzyme system conjugates bilirubin and many drugs with glucuronic acid in the hepatic endoplasmic reticulum?

• A Sulphotransferases (SULTs) using 3'-phosphoadenosine-5'-phosphosulphate (PAPS)
• B Glutathione S-transferases (GSTs) using glutathione for electrophile conjugation
• C N-acetyltransferases (NATs) using acetyl-CoA for acetylation
• D UDP-glucuronosyltransferases (UGTs) using UDP-glucuronic acid as the glucuronyl donor ✓

Explanation

UDP-glucuronosyltransferases (UGTs) are ER-localised enzymes that transfer glucuronic acid from UDP-glucuronic acid to hydroxyl, carboxyl, amino, or sulphhydryl groups on xenobiotics and endogenous compounds including bilirubin, bile acids, thyroid hormones, and steroids. The glucuronide product is water-soluble and excreted in bile or urine. UGT1A1 is specifically responsible for bilirubin glucuronidation; its reduced expression causes Gilbert syndrome and Crigler-Najjar. SULTs use PAPS for sulphation. GSTs conjugate reactive electrophiles with glutathione. NATs perform acetylation (e.g., isoniazid, procainamide); slow acetylators have more drug toxicity.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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