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In the phagolysosome period, hemoglobin (Hb) is broken down to release heme or haem. Free heme is degraded to biliverdin, carbon monoxide (CO) and ferrous iron by the endoplasmic reticulum enzymes, haem oxygenase-1 or haem oxygenase-2. Biliverdin is reduced to bilirubin by biliverdin reductase. Similarly, free extracellular heme transported into macrophages/microglias is also broken down to produce free iron, biliverdin (bilirubin), and CO.
