Heme degradation by reactive oxygen species.
Heme proteins play a major role in various biological functions, such as oxygen sensing, electron transport, signal transduction, and antioxidant defense enzymes. Most of these reactions are carried out by redox reactions of heme iron. As the heme is not recycled, most cells containing heme proteins have the microsomal mixed function oxygenase, heme oxygenase, which enzymatically degrades heme to biliverdin, carbon monoxide, and iron. However, the red cell with the largest pool of heme protein, hemoglobin, contains no heme oxygenase, and enzymatic degradation of the red cell heme occurs only after the senescent red cells are removed by the reticuloendothelial system. Therefore, only nonenzymatic heme degradation initiated when the heme iron undergoes redox reactions in the presence of oxygen-producing reactive oxygen species takes place in the red cell. Unlike enzymatic degradation, which specifically attacks the alpha-methene bridge, reactive oxygen species randomly attack all the carbon methene bridges of the tetrapyrrole rings, producing various pyrrole products in addition to releasing iron. This review focuses on the literature related to nonenzymatic heme degradation with special emphasis on hemoglobin, the dominant red cell heme protein.
Nagababu
Enika
E
Molecular Dynamics Section, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. enikan@grc.nia.nih.gov
Rifkind
Joseph M
JM
D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D004730:Endothelium, Vascular / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D006418:Heme / Q000737:chemistry*; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007501:Iron / Q000737:chemistry; D008956:Models, Chemical; D010100:Oxygen / Q000378:metabolism; D011524:Protoporphyrins / Q000737:chemistry; D017382:Reactive Oxygen Species
D000975:Antioxidants; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D006418:Heme; D006861:Hydrogen Peroxide; D007501:Iron; D010100:Oxygen