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Hemoglobin breakdown : Each RBC contains hemoglobin (Hb), 1 which is broken down into: Globin degraded into amino acids (reused) Heme further metabolized into: 2 Iron (Fe) stored as ferritin or hemosiderin or recycled for new RBC synthesis Protoporphyrin ring converted to biliverdin by the enzyme heme oxygenase 3 Biliverdin reduced to unconjugated (indirect) bilirubin by biliverdin reductase 4 Unconjugated bilirubin in plasma: Unconjugated bilirubin is lipophilic and water-insoluble