The role of the thiol group in protein modification with methylglyoxal

• Main Authors: Aćimović Jelena M., Stanimirović Bojana D., Mandić Ljuba M.
• Format: Article
• Language: English
• Published: Serbian Chemical Society 2009-01-01
• Series: Journal of the Serbian Chemical Society
• Subjects: methylglyoxal; protein thiol group reaction; protein modification and cross-linking; ages
• Online Access: http://www.doiserbia.nb.rs/img/doi/0352-5139/2009/0352-51390909867A.pdf
• ISSN: 0352-5139; 1820-7421

Methylglyoxal is a highly reactive α-oxoaldehyde with elevated production in hyperglycemia. It reacts with nucleophilic Lys and Arg side-chains and N-terminal amino groups causing protein modification. In the present study, the importance of the reaction of the Cys thiol group with methylglyoxal in protein modification, the competitiveness of this reaction with those of amino and guanidine groups, the time course of these reactions and their role and contribution to protein cross-linking were investigated. Human and bovine serum albumins were used as model systems. It was found that despite the very low levels of thiol groups on the surface of the examined protein molecules (approx. 80 times lower than those of amino and guanidino groups), a very high percentage of it reacts (25-85 %). The amount of reacted thiol groups and the rate of the reaction, the time for the reaction to reach equilibrium, the formation of a stable product and the contribution of thiol groups to protein cross-linking depend on the methylglyoxal concentration. The product formed in the reaction of thiol and an insufficient quantity of methylglyoxal (compared to the concentrations of the groups accessible for modification) participates to a significant extent (4 %) to protein cross-linking. Metformin applied in equimolar concentration with methylglyoxal prevents its reaction with amino and guanidino groups but, however, not with thiol groups.