Category: catabolism
Senescent RBCs phagocytosed by reticuloendothelial macrophages → heme oxygenase (HO-1 inducible + HO-2 constitutive) cleaves heme → biliverdin + CO (free!) + Fe2+ (recycled via transferrin). Biliverdin reductase → unconjugated bilirubin (lipid-soluble, albumin-bound). Hepatic uptake → UGT1A1 conjugation with glucuronic acid → conjugated bilirubin (water-soluble; biliary excretion). Intestinal bacteria deconjugate + reduce to urobilinogen → ~80% excreted as stercobilin (fecal color); ~20% absorbed + recycled / renally excreted as urobilinogen (urine color). Clinical: Gilbert syndrome = UGT1A1 promoter polymorphism → mild unconjugated hyperbilirubinemia (~5% population; benign; can present with fasting/stress jaundice); Crigler-Najjar = severe UGT1A1 deficiency (autosomal recessive). Atazanavir + indinavir inhibit UGT1A1 → unconjugated hyperbilirubinemia + scleral icterus (benign).