The Road to Advanced Glycation End Products: A Mechanistic Perspective

Abstract

Protein glycation is a slow natural process involving the chemical modification of the reactive amino and guanidine functions in amino acids by sugars and carbohydrates-derived reactive carbonyls. Its deleterious consequences are obvious in the case of long-lived proteins in aged people and are exacerbated by the high blood concentration of sugars in diabetic patients. The non-enzymatic glycation of proteins occurs through a wide range of concurrent processes comprising condensation, rearrangement, fragmentation, and oxidation reactions. Using a few well established intermediates such as Schiff base, Amadori product and reactive a-dicarbonyls as milestones and the results of in vitro glycation investigations, an overall detailed mechanistic analysis of protein glycation is presented for the first time. The pathways leading to several advanced glycation end products (AGEs) such as (carboxymethyl)lysine, pentosidine, and glucosepane are outlined, whereas other AGEs useful as potential biomarkers of glycation are only briefly mentioned. The current stage of the development of glycation inhibitors has been reviewed with an emphasis on their mechanism of action.

Accumulation of thymidine-derived sugars in thymidine phosphorylase overexpressing cells

“…adding sugar moieties to proteins by non-enzymatic reactions [29,30]. However, whether protein glycation of AGEs are formed in the cells used in our study, remains to be identified.…”

Glycated Albumin Modulates Endothelial Cell Thrombogenic and Inflammatory Responses

“…Some claim that a Schiff base is irreversible (glycation time of 1-2 weeks), whereas others claim that the products must pass to the Amadori rearrangement to be fully glycated (6-8 weeks of glycation). 5,6 Regardless, AGEs perpetuate many deleterious effects associated with cardiovascular complications during diabetes.…”

Inhibitory effect of gold nanoparticles on the D-ribose glycation of bovine serum albumin

“…Peak 1 and peak 2 in each of the profiles represent the fluorescent AGE products of BSA detectable at excitation and emission wavelengths of 360 nm and 420 nm, respectively. 33,35 Repeat HPLC analysis showed that these peaks occurred routinely in all mixtures designated A and B. Peak 1 had a retention time of 2.25 minutes and peak 2 had a retention time of 15.87 min.…”

“…All samples yielded a prominent UV absorption at around 280 nm, which was attributed to the formation of AGEs and their aromatic ring structures. 33 Figure 2A and B display the time course UV absorption profiles of all colloidal suspensions. The UV profiles show three important findings: 1) that UV intensities increased over time, 2) that UV absorption readings were highest in samples that contained no GNPs but only BSA and D-ribose, and 3) that the extent inhibition of glycation was relatable to the colloidal suspension's total surface area.…”