ADP-ribose in glycation and glycoxidation reactions

Adv Exp Med Biol. 1997:419:371-9. doi: 10.1007/978-1-4419-8632-0_49.

Abstract

Glycation is initiated by reaction of a reducing sugar with a protein amino group to generate a Schiff base adduct. Following an Amadori rearrangement to form a ketoamine adduct, a complex chemistry involving oxidation often leads to protein glycoxidation products referred to as advanced glycosylation end products (AGE). The AGE include protein carboxymethyllysine (CML) residues and a heterogeneous group of complex modifications characterized by high fluorescence and protein-protein cross links. The sugar sources for the glycoxidation of intracellular proteins are not well defined but pentoses have been implicated because they are efficient precursors for the formation of the fluorescent AGE, pentosidine. ADP-ribose, generated from NAD by ADP-ribose transfer reactions, is a likely intracellular source of a reducing pentose moiety. Incubation of ADP-ribose with histones results in the formation of ketoamine glycation conjugates and also leads to the rapid formation of protein CML residues, histone H1 dimers, and highly fluorescent products with properties similar to the AGE. ADP-ribose is much more efficient than other possible pentose donors for glycation and glycoxidation of protein amino groups. Recently developed methods that differentiate nonenzymic modifications of proteins by ADP-ribose from enzymic modifications now allow investigations to establish whether some protein modifications by monomers of ADP-ribose in vivo represent glycation and glycoxidation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism*
  • Arginine / metabolism
  • Fluorescence
  • Glycation End Products, Advanced / metabolism
  • Glycosylation
  • Hexosamines / metabolism
  • Histones / metabolism
  • Humans
  • Ketoses / metabolism
  • Lysine / metabolism
  • Oxidation-Reduction

Substances

  • Glycation End Products, Advanced
  • Hexosamines
  • Histones
  • Ketoses
  • Adenosine Diphosphate Ribose
  • Arginine
  • Lysine