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Heme oxygenase 2 (HO-2) cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of HO-2 is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed. HO-2 is implicated in the production of carbon monoxide in brain where it could act as a neurotransmitter.