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 Leuco nostoc mesenteroides with the lipid peroxidation product 4-hydroxy-2-n onenal leads to the formation of cross-linked protein. This is accompa nied by the appearance of protein-associated fluorescence with excitat ion and emission maxima of 340 and 415 nm, respectively, and with the disappearance of histidine and lysine residues. Cross-linked protein i s less susceptible than native Glu-6-PDH to proteolysis by the multica talytic protease, a multienzymic proteolytic complex involved in the i ntracellular degradation of damaged proteins. In addition, 4-hydroxy-2 -nonenal-modified Glu-6-PDH inhibits the multicatalytic protease and c an therefore prevent the efficient degradation of oxidized protein. Th ese findings may have important implications for the accumulation of a ltered protein and fluorescent material in vivo, processes that are be lieved to be involved in age- and disease-related impairment of cellul ar function.