Modification of glucose-6-phosphate dehydrogenase by 4-hydroxy-2-nonenal. Formation of cross-linked protein that inhibits the multicatalytic protease.
Incubation of glucose-6-phosphate dehydrogenase (Glu-6-PDH) from Leuconostoc mesenteroides with the lipid peroxidation product 4-hydroxy-2-nonenal leads to the formation of cross-linked protein. This is accompanied by the appearance of protein-associated fluorescence with excitation and emission maxima of 340 and 415 nm, respectively, and with the disappearance of histidine and lysine residues. Cross-linked protein is less susceptible than native Glu-6-PDH to proteolysis by the multicatalytic protease, a multienzymic proteolytic complex involved in the intracellular degradation of damaged proteins. In addition, 4-hydroxy-2-nonenal-modified Glu-6-PDH inhibits the multicatalytic protease and can therefore prevent the efficient degradation of oxidized protein. These findings may have important implications for the accumulation of altered protein and fluorescent material in vivo, processes that are believed to be involved in age- and disease-related impairment of cellular function.
Friguet
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B
Laboratory of Biochemistry, NHLBI, National Institutes of Health, Bethesda, Maryland 20892.
Stadtman
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ER
Szweda
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LI
D000447:Aldehydes / Q000737:chemistry*; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D007934:Leuconostoc / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008956:Models, Chemical; D009097:Multienzyme Complexes / Q000378:metabolism*; D011480:Protease Inhibitors / Q000737:chemistry*; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry
D000447:Aldehydes; D000596:Amino Acids; D003432:Cross-Linking Reagents; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D005954:Glucosephosphate Dehydrogenase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C027576:4-hydroxy-2-nonenal