Myoglobin scavenges peroxynitrite without being significantly nitrated.
We have analyzed in detail hemoglobin (Hb) and myoglobin (Mb) after treatment of different forms of these proteins with variable amounts of peroxynitrite. HPLC analyses of the peroxynitrite-treated proteins subjected either to acid hydrolysis or Pronase digestion showed that only very low quantities of 3-nitrotyrosine are formed when equivalent amounts of peroxynitrite are allowed to react with the oxy form of these proteins. Comparable amounts of nitrated amino acids are formed when metMb and metHb are treated with peroxynitrite under analogous conditions, but significantly larger yields are observed with apoMb and metMbCN. Interestingly, in addition we found that also the tryptophan residues of Mb and Hb are nitrated to a low but detectable extent. Taken together, our data suggest that the heme center of Mb may act as an efficient scavenger of peroxynitrite, protecting the globin from nitration. As peroxynitrite can irreversibly inhibit cytochrome c oxidase, oxyMb may utilize an additional important pathway to maintain mitochondrial respiration, that is, rapidly react with peroxynitrite and thus prevent nitration of other cellular components.
Herold
Susanna
S
Laboratorium für Anorganische Chemie, Eidgenössische Technische Hochschule, ETH Hönggerberg, CH-8093 Zürich, Switzerland. herold@inorg.chem.ethz.ch
Shivashankar
Kalinga
K
Mehl
Martin
M
D000818:Animals; D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D016166:Free Radical Scavengers / Q000737:chemistry* / Q000378:metabolism; D005914:Globins / Q000032:analysis; D007150:Immunohistochemistry; D008786:Metmyoglobin / Q000737:chemistry / Q000378:metabolism; D009211:Myoglobin / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D009566:Nitrates / Q000737:chemistry* / Q000378:metabolism; D010108:Oxyhemoglobins / Q000737:chemistry / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000737:chemistry* / Q000378:metabolism; D014364:Tryptophan / Q000032:analysis / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism
D001059:Apoproteins; D016166:Free Radical Scavengers; D009211:Myoglobin; D009566:Nitrates; D010108:Oxyhemoglobins; C010857:apomyoglobin; C017595:oxymyoglobin; D008786:Metmyoglobin; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D014364:Tryptophan; D005914:Globins