Enzymic Repair and Prevention of Chemical Aging by the Maillard reaction in Vivo
Vincent M. Monnier, David R. Sell, Xinle Wu, Dai Zhenyu
Departments of Pathology and Biochemistry, Case Western Reserve University, Cleveland, Ohio 44016, USA
The Maillard Reaction is the reaction that occurs between carbonyl
compounds stemming from the reaction of reducing sugars and oxidized
lipids with proteins, DNA and other nucleophiles to form advanced
glycation endproducts (AGEs) and crosslinks. Recent data from our
laboratory has identified glucosepane, a lysyl-arginine crosslink, as
the single major protein crosslink from glucose in aging human
collagen. In related studies ornithine was found to accumulate in aging
lens and skin proteins, resulting most likely from oxoaldehyde attack
onto arginine residues and spontaneous deguanidination. These two
modifications together with carboxymethyl-lysine, a biologically active
AGE, inflict extensive tissue damage during aging and in age-related
diseases. In order to search for genetic approaches for reversing the
damage, we isolated enzymes from soil organisms that can grow on
glycated (Amadori) products. Two amadoriases which deglycate free
substrates by oxidative cleavage were isolated, biochemically
characterized, and cloned. These studies will be discussed and
contrasted with another enzyme family, i.e. fructosylamine 3-kinases
that can deglycate intracellular proteins upon phosphorylation of the
substrate, as well as chemical approaches to block glucose mediated
crosslinking in vivo.
Key words:
glycation, collagen, lens crystallins, diabetes, aging
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