Phase II biotransformation reactions conjugate drugs/xenobiotics to endogenous molecules. Glucuronidation requires UDP-glucuronic acid. A newborn has physiological jaundice partly because:

• A Neonatal hepatocytes express fetal albumin with lower bilirubin-binding capacity
• B Neonatal erythrocytes express fetal hemoglobin which is catabolised more rapidly than adult Hb
• C UDP-glucuronosyltransferase 1A1 (UGT1A1) activity is low in neonatal liver, impairing bilirubin conjugation ✓
• D Neonatal kidneys cannot excrete indirect bilirubin due to immature organic anion transporters

Explanation

Bilirubin conjugation to bilirubin diglucuronide (the water-soluble form) depends on hepatic UDP-glucuronosyltransferase 1A1 (UGT1A1). At birth, UGT1A1 enzyme activity is approximately 0.1–1% of adult levels and takes several weeks to mature. This enzymatic immaturity causes unconjugated (indirect) hyperbilirubinemia in the first few days of life. Gilbert's syndrome involves a UGT1A1 promoter polymorphism (TA repeat), which illustrates that even partial UGT1A1 reduction causes benign hyperbilirubinemia. Crigler-Najjar syndrome type I involves complete absence of UGT1A1.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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