title: Modification and inactivation of human Cu,Zn-superoxide dismutase by methylglyoxal.
abstract: Methylglyoxal (MG) has been identified as an intermediate in non-enzymatic glycation, and increased levels have been reported in patients with diabetes. In this study, the effect of MG on the structure and function of human Cu,Zn-superoxide dismutase (SOD) was investigated. MG modifies Cu,Zn-SOD, as indicated by the formation of fluorescent products. When Cu, Zn-SOD was incubated with MG, covalent crosslinking of the protein increased progressively. MG-mediated modification of Cu,Zn-SOD led to loss of enzymatic activity and release of copper ions from the protein. Radical scavengers inhibited the crosslinking of Cu,Zn-SOD. When Cu,Zn-SOD that had been exposed to MG was analyzed, glycine, histidine, lysine, and valine residues were found to be particularly sensitive. It is suggested that oxidative damage to Cu,Zn-SOD by MG may perturb cellular antioxidant defense systems and damage cells. This effect may account, in part, for organ deterioration in diabetes.
authors.affiliation: Department of Genetic Engineering, Chongju University, Chongju 360-764, Korea. jhkang@chongju.ac.kr
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Kang
mesh_terms: D003432:Cross-Linking Reagents / Q000378:metabolism; D006801:Humans; D011765:Pyruvaldehyde / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D011765:Pyruvaldehyde; D013482:Superoxide Dismutase