Mechanisms of action of malondialdehyde and 4-hydroxynonenal on xanthine oxidoreductase.
Studies have been made on the possible involvement of malondialdehyde (MDA) and (E)-4-hydroxynon-2-enal (HNE), two terminal compounds of lipid peroxidation, in modifying xanthine oxidoreductase activity through interaction with the oxidase (XO) and/or dehydrogenase (XDH) forms. The effect of the two aldehydes on XO (reversible, XO(rev), and irreversible, XO(irr)) and XDH was studied using xanthine oxidase from milk and xanthine oxidoreductase partially purified from rat liver. The incubation of milk xanthine oxidase with these aldehydes resulted in the inactivation of the enzyme following pseudo-first-order kinetics: enzyme activity was completely abolished by MDA (0.5-4 mM), while residual activity (5% of the starting value) associated with an XO(irr) form was always observed when the enzyme was incubated in the presence of HNE (0.5-4 mM). The addition of glutathione to the incubation mixtures prevented enzyme inactivation by HNE. The study on the xanthine oxidoreductase partially purified from rat liver showed that MDA decreases the total enzyme activity, acting only with the XO forms. On the contrary HNE leaves the same level of total activity but causes the conversion of XDH into an XO(irr) form.
Cighetti
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Department of Medical Chemistry and Biochemistry, Faculty of Medicine, University of Milan, Via Saldini 50, 20133 Milan, Italy. Giuliana.Gighetti@unimi.it
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D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008315:Malondialdehyde / Q000494:pharmacology*; D008892:Milk / Q000201:enzymology; D051381:Rats; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D000447:Aldehydes; D004791:Enzyme Inhibitors; D008315:Malondialdehyde; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D005978:Glutathione; C027576:4-hydroxy-2-nonenal