In vivo glycation of aldehyde reductase, a major 3-deoxyglucosone reducing enzyme: identification of glycation sites.
We have reported that the enzyme which reduces 3-deoxyglucosone (3-DG), a major intermediate and a potent cross-linker in the Maillard reaction, is identical with aldehyde reductase [Takahashi, M., Fujii, J., Teshima, T., Suzuki, K., Shiba, T., & Taniguchi, N. (1993) Gene 127, 249-253]. The enzyme purified from normal rat liver was found to be partially glycated as judged by binding to a boronate column and reactivity to anti-epsilon-hexitol lysine IgG. Sites of in vivo glycation of rat liver aldehyde reductase were identified by sequencing of digested peptides labeled with NaB[3H]4 and by mass spectrometry. The major glycated sites were lysines 67, 84, and 140. The glycated enzyme had low catalytic efficiency (kcat/Km) as compared to the nonglycated form. In streptozotocin-induced diabetic rats, the glycated form was significantly increased in kidneys. Because the enzyme plays a role in detoxifying 3-DG formed through the Maillard reaction in vivo, glycation of aldehyde reductase and reduction of its activity may result in the metabolic imbalance under diabetic conditions.
Takahashi
M
M
Department of Biochemistry, Osaka University Medical School, Japan.
Lu
Y B
YB
Myint
T
T
Fujii
J
J
Wada
Y
Y
Taniguchi
N
N
D000449:Aldehyde Reductase / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D006031:Glycosylation; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010449:Peptide Mapping; D011499:Protein Processing, Post-Translational; D051381:Rats
D003847:Deoxyglucose; D000449:Aldehyde Reductase; C016350:3-deoxyglucosone