 Degradation begins inside macrophages of the spleen, which remove old and damaged (senescent) erythrocytes from the circulation.In the first step, heme is converted to biliverdin by the enzyme heme oxygenase (HMOX).NADPH is used as the reducing agent, molecular oxygen enters the reaction, carbon monoxide (CO) is produced and the iron is released from the molecule as the ferrous ion (Fe2+).