Ovothiols as free-radical scavengers and the mechanism of ovothiol-promoted NAD(P)H-O2 oxidoreductase activity.
Racemic ovothiol A [(+/-)-1a] and the ovothiol model compound 1,5-dimethyl-4-mercaptoimidazole (DMI, 2) were found to scavange the free radicals Fremy's salt (4) and Banfield' radical (5) much more rapidly than did the thiol antioxidant glutathione. Ovothiol A also scavenges the tyrosyl radical, with efficiency comparable to that of ascorbic acid and the tocopherol analogue trolox (3). The ovothiol model compound DMI was found to scavenge superoxide with a rate constant comparable to that of the reaction between superoxide and glutathione. These results suggest both a free-radical scavenging role for the ovothiols and a mechanism by which the ovothiols confer NAD(P)H-O2 oxidoreductase activity upon the enzyme ovoperoxidase. Investigation of this mechanism implicates the ovothiol thiyl radical and the NAD radical as key intermediates. The ovothiyl radical appears to be unreactive toward oxygen but highly reactive toward NADH. An estimate of the one-electron oxidation potential of the ovothiol anion is presented. The physical basis for the stability of the ovothiol free radical is discussed.
Holler
T P
TP
Department of Chemistry, University of Washington, Seattle 98195.
Hopkins
P B
PB
D000603:Amino Acids, Sulfur / Q000494:pharmacology*; D000975:Antioxidants; D001205:Ascorbic Acid; D002839:Chromans; D005609:Free Radicals; D005978:Glutathione; D007202:Indicators and Reagents; D007700:Kinetics; D008762:Methylhistidines; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D019255:NADPH Oxidases; D009603:Nitroso Compounds; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds
D000603:Amino Acids, Sulfur; D000975:Antioxidants; D002839:Chromans; D005609:Free Radicals; D007202:Indicators and Reagents; D008762:Methylhistidines; D009603:Nitroso Compounds; D013438:Sulfhydryl Compounds; C050085:ovothiol C; C001259:Fremy's salt; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C022709:superoxide-forming enzyme; D005978:Glutathione; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid