Metal-catalyzed inactivation of bovine glucose-6-phosphate dehydrogenase--role of thiols.
The role of thiols as oxidant scavengers during inactivation of bovine glucose-6-phosphate dehydrogenase by metal-catalyzed oxidation systems has been studied in vitro. Partial inactivation of the enzyme was achieved by the metal-catalyzed oxidation systems Fe(II)/H202/EDTA or Fe(II)/H202/ADP under specific conditions. When EDTA as chelator was present in the oxidation system, both cysteine and N-acetylcysteine at low concentrations (0.1-1 mM) drastically enhanced inactivation, while cysteinyl-glycine and glutathione did not. The thiol-mediated inactivation was inhibitable by superoxide dismutase. Depletion of enzyme activity by cysteine was paralleled by an increase of the carbonyl content, which indicates oxidative injury. However, when EDTA as chelator was replaced by the natural chelator ADP, all thiols studied acted as antioxidants. It is therefore concluded that the nature of the chelator as a constituent of the metal-catalyzed oxidation systems determines whether the antioxidative function of some thiols is shifted to a prooxidative function against glucose-6-phosphate dehydrogenase.
GSF--National Research Center for Environment and Health, Institute of Inhalation Biology, Neuherberg, Germany.
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D000111:Acetylcysteine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D003545:Cysteine / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004492:Edetic Acid / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005954:Glucosephosphate Dehydrogenase / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D019271:Hypoxanthine / Q000378:metabolism / Q000494:pharmacology; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D008670:Metals / Q000378:metabolism*; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000378:metabolism / Q000494:pharmacology
D004151:Dipeptides; D008670:Metals; D013438:Sulfhydryl Compounds; D019271:Hypoxanthine; C028505:cysteinylglycine; D000244:Adenosine Diphosphate; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D007501:Iron; D005954:Glucosephosphate Dehydrogenase; D014969:Xanthine Oxidase; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine