title: Why heme needs to be degraded to iron, biliverdin IXalpha, and carbon monoxide?
abstract: A large amount of hemoglobin is degraded daily to heme and globin and is replenished by biosynthesis in the bone marrow erythroblasts. "Free heme" can be dissociated from apohemoglobin in vitro and, conversely, native hemoglobin can be renatured from them. Then why does heme need to be degraded to iron, biliverdin IXalpha, and carbon monoxide in vivo? Free heme, i.e., a protein-unbound heme, exists in cells at a very minute concentration and exerts regulatory functions such as the repression of nonspecific delta-aminolevulinate synthase expression and the induction of microsomal heme oxygenase-1 (HO-1). The latter gene expression occurs by way of free heme-mediated derepression of Bach1, a mammalian heme-responsive transcription factor that suppresses the activation of the HO-1 gene. All these events occur at free heme concentrations below 1 microM. In contrast, free heme concentration greater than 1 microM can be toxic because it catalyzes the production of reactive oxygen species. To cope with this problem, the body is equipped with various defense mechanisms against high free heme concentrations. HO is one of the major players in these mechanisms, and it catabolizes free heme to iron, biliverdin IXalpha, and carbon monoxide. These three metabolites of heme by HO reactions have additional important functions and are involved in various critical cellular events. Thus, the breakdown of heme to smaller elements has its own significance in essential cellular metabolism.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sassa
mesh_terms: D001664:Biliverdine / Q000378:metabolism*; D002248:Carbon Monoxide / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism
chemical_list: D006454:Hemoglobins; D007527:Isoenzymes; D006418:Heme; D002248:Carbon Monoxide; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); D001664:Biliverdine