Glycation, glycoxidation, and cross-linking of collagen by glucose. Kinetics, mechanisms, and inhibition of late stages of the Maillard reaction
Glycation, glycoxidation, and cross-linking of collagen by glucose. Kinetics, mechanisms, and inhibition of late stages of the Maillard reaction. M X Fu , K J Wells-Knecht , J A Blackledge , T J Lyons , S R Thorpe and J W Baynes Department of Chemistry and Biochemistry, University of South Carolina,...
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Published in | Diabetes (New York, N.Y.) Vol. 43; no. 5; pp. 676 - 683 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
American Diabetes Association
01.05.1994
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Online Access | Get full text |
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Summary: | Glycation, glycoxidation, and cross-linking of collagen by glucose. Kinetics, mechanisms, and inhibition of late stages of
the Maillard reaction.
M X Fu ,
K J Wells-Knecht ,
J A Blackledge ,
T J Lyons ,
S R Thorpe and
J W Baynes
Department of Chemistry and Biochemistry, University of South Carolina, Columbia 29208.
Abstract
The Maillard or browning reaction between sugar and protein contributes to the increased chemical modification and cross-linking
of long-lived tissue proteins in diabetes. To evaluate the role of glycation and oxidation in these reactions, we have studied
the effects of oxidative and antioxidative conditions and various types of inhibitors on the reaction of glucose with rat
tail tendon collagen in phosphate buffer at physiological pH and temperature. The chemical modifications of collagen that
were measured included fructoselysine, the glycoxidation products N epsilon-(carboxymethyl)lysine and pentosidine and fluorescence.
Collagen cross-linking was evaluated by analysis of cyanogen bromide peptides using sodium dodecyl sulfate-polyacrylamide
gel electrophoresis and by changes in collagen solubilization on treatment with pepsin or sodium dodecylsulfate. Although
glycation was unaffected, formation of glycoxidation products and cross-linking of collagen were inhibited by antioxidative
conditions. The kinetics of formation of glycoxidation products proceeded with a short lag phase and were independent of the
amount of Amadori adduct on the protein, suggesting that autoxidative degradation of glucose was a major contributor to glycoxidation
and cross-linking reactions. Chelators, sulfhydryl compounds, antioxidants, and aminoguanidine also inhibited formation of
glycoxidation products, generation of fluorescence, and cross-linking of collagen without significant effect on the extent
of glycation of the protein. We conclude that autoxidation of glucose or Amadori compounds on protein plays a major role in
the formation of glycoxidation products and cross-liking of collagen by glucose in vitro and that chelators, sulfhydryl compounds,
antioxidants, and aminoguanidine act as uncouplers of glycation from subsequent glycoxidation and cross-linking reactions. |
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ISSN: | 0012-1797 1939-327X 0012-1797 |
DOI: | 10.2337/diabetes.43.5.676 |