Assessing the potential of carboxylic acids as inhibitors of glycation

• Main Author: Gao, Hong Ying, 1967-
• Format: Others
• Language: en
• Published: McGill University 2008
• Subjects: Glycosylation.; Lysozyme.; Carboxylic acids.; Maillard reaction > Physiological aspects.
• Online Access: http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116072

Glycation is a series of chemical interactions occurring in food and biological systems between reducing sugars and proteins leading to the formation of Advanced Glycation End products (AGEs). Ingestion of dietary AGEs and/or their formation in-vivo are mainly associated with cardiovascular and other age-related diseases and complications of long term diabetes. Potential strategies to prevent AGE formation can help to reduce risk factors associated with thermal processing of many foods. The overall objective of this research was focused on the identification of potential AGE inhibitors and investigation of their activity in glucose and ribose-based model systems containing lysozyme. The carboxylic acid functional group was chosen as a potential candidate based on their ability to interact with Schiff bases in addition to their ability to form amide bonds and carboxylate salts with the lysine side chains of proteins. The model systems were incubated with and without selected carboxylic acids (maleic, acetic, oxalic and citraconic) at 50°C for 12, 24 and 48h at pH 6.5. The effect of carboxylic acids on the glycation of lysozyme was studied by electrospray ionization mass spectrometry (ESI-MS). The experimental results showed that none of the carboxylic acids were able to form amide linkages with lysozyme under the experimental conditions and only maleic acid was able to form carboxylate salts, however, oxalic acid was the only acid able to interact with the Schiff base and form 1,3-oxazolidine-4,5-dione intermediate and thus hinder its rearrangement into Amadori product and consequently inhibit glycation. As a result the percentage of free or unreacted lysozyme was the highest in oxalic acid model systems (9.4% in the case of glucose, 7.1% in the case of ribose system) and was even higher than the control systems (6.0% in the case of glucose, 1.2% in the case of ribose system) of both glucose and ribose. In addition, all carboxylic acids were able to modify the relative distribution of different glycoforms generated during the incubation period however oxalic acid was the most efficient in shifting the distribution of glycoforms to lower molecular weight clusters which can additionally contribute to its anti-glycation activity.