The role of nonenzymatic glycosylation, transition metals, and free radicals in the formation of collagen aggregates.
Incubation of corneal collagen type I with glucose in the presence of transition metal ions (copper, iron) results in the formation of collagen aggregates insoluble in 6 M urea, and in 2% sodium dodecyl sulfate + 5% beta-mercaptoethanol. The reaction is mediated by hydrogen peroxide and transition metals since it is inhibited by catalase and by the chelating agent diethylenetriaminepentaacetic acid. Comparative studies showed that copper is more efficient than iron and that the reaction proceeds more rapidly with ribose than with glucose. The data support a mechanism involving transition metal ion catalyzed autoxidation of glucose (and possibly of Amadori products) with generation of superoxide radical. Superoxide dismutation produces hydrogen peroxide, which then generates hydroxyl radicals in the presence of transition metal ions (Fenton reaction). Hydroxyl radical attack is known to lead to cross-linking, which is enhanced in glycated proteins. The experimental data presented are consistent with in vivo alteration of collagen properties during normal aging and with the acceleration of similar changes in diabetes mellitus.
Chace
K V
KV
Dean A. McGee Eye Institute, Oklahoma City, OK 73104.
Carubelli
R
R
Nordquist
R E
RE
D000818:Animals; D003094:Collagen / Q000187:drug effects / Q000378:metabolism*; D003300:Copper / Q000494:pharmacology; D019327:Copper Sulfate; D003315:Cornea / Q000378:metabolism; D005609:Free Radicals; D005947:Glucose / Q000494:pharmacology; D006031:Glycosylation; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D046911:Macromolecular Substances; D008623:Mercaptoethanol / Q000494:pharmacology; D011817:Rabbits; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D014508:Urea / Q000494:pharmacology
D005609:Free Radicals; D046911:Macromolecular Substances; D012967:Sodium Dodecyl Sulfate; D008623:Mercaptoethanol; D003300:Copper; D014508:Urea; D003094:Collagen; D006861:Hydrogen Peroxide; D005947:Glucose; D019327:Copper Sulfate