4-Hydroxynonenal inhibits glutathione peroxidase: protection by glutathione.
4-Hydroxy-2,3-trans-nonenal, a lipid peroxidation product, inhibits glutathione peroxidase in a concentration-dependent manner. The concentration providing 50% inhibition is 0.12 mM. This inhibition can be almost completely (89%) prevented by 1 mM glutathione added to the incubation mixture 30 min before 4-hydroxy-2,3-trans-nonenal or 2,3-trans-nonenal, but not by other thiol-containing antioxidants such as 0.5 mM dithiothreitol or beta-mercaptoethanol. Again the addition of 1 mM glutathione, and not of 0.5 mM dithiothreitol or beta-mercaptoethanol, to the enzyme 30 min after incubation with 4-hydroxy-2,3-trans-nonenal restores activity to the same extent as does the preincubation with GSH. In view of the known reactivity of 4-hydroxy-2,3-trans-nonenal with lysine residues and the reversibility of the inhibition, the involvement of a lysine residue in GSH binding to glutathione peroxidase is proposed. The potential relevance of the inhibition of glutathione peroxidase by 4-hydroxy-nonenal to oxidative tissue damage is discussed with particular emphasis on neurological disorders.
Department of Physiology, School of Medicine & Dentistry, University of Valencia, Spain.
F
F
Bosch-Morell
L
L
Flohé
N
N
Marín
F J
FJ
Romero
D000447:Aldehydes / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology
D000447:Aldehydes; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D005979:Glutathione Peroxidase; D005978:Glutathione; C027576:4-hydroxy-2-nonenal