Enzymatic deglycation of proteins.
Reducing sugars such as glucose react with amino groups in proteins to form the Amadori product, which can undergo a wide range of chemical modifications and form cross-links in tissue proteins. There is growing evidence to suggest that accumulation of glycation products is associated with aging and disease progression, as in diabetes. Thus, the design and discovery of inhibitors for the glycation cascade would potentially offer a promising therapeutic approach for the prevention of glycation related diseases, especially diabetes. Two types of enzymes, fructosyl lysine oxidase and fructose lysine 3-phosphokinase, catalyze the deglycation reaction and generate free amine groups. This paper reviews the biochemical properties of these "amadoriase" enzymes, such as structural-function relationship, kinetic mechanism, and substrate specificity, as well as their biological roles and applications in the protein deglycation.
Wu
Xinle
X
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Monnier
Vincent M
VM
D000594:Amino Acid Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D005544:Forecasting; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D017127:Glycation End Products, Advanced; D007527:Isoenzymes; D011506:Proteins; D000594:Amino Acid Oxidoreductases; C103012:amadoriase