Putative denitrosylase activity of Cu,Zn-superoxide dismutase.
The Cu,Zn-superoxide dismutase (SOD1) has been reported to exert an S-nitrosylated glutathione (GSNO) denitrosylase activity that was augmented by a familial amyotrophic lateral sclerosis (FALS)-associated mutation in this enzyme. This putative enzymatic activity as well as the spontaneous decomposition of GSNO has been reexamined. The spontaneous decomposition of GSNO exhibited several peculiarities, such as a lag phase followed by an accelerating rate plus a marked dependence on GSNO concentration, suggestive of autocatalysis, and a greater rate in polypropylene than in glass vessels. Dimedone caused a rapid increase in absorbance likely due to reaction with GSNO, followed by a slower increase possibly due to reaction with an intermediate such as glutathione sulfenic acid. SOD1 weakly increased the rate of decomposition of GSNO, but did so only when GSH was present; and FALS-associated mutant forms of SOD1 were not more active in this regard than was the wild type. Decomposed GSNO, when added to fresh GSNO, hastened its decomposition, in accord with autocatalysis, and when added to GSH, generated GSNO in accord with the presence of nitrite. A mechanism is proposed that is in accord with these observations.
Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
Ayako
A
Okado-Matsumoto
Irwin
I
Fridovich
D003512:Cyclohexanones / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009154:Mutation / Q000235:genetics; D009584:Nitrogen / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D003512:Cyclohexanones; C004774:dimedone; D010105:Oxygenases; D013482:Superoxide Dismutase; D005978:Glutathione; D009584:Nitrogen