Advanced glycation endproduct
Advanced Glycation Endproducts (AGEs) are the result of a chain of chemical reactions after an initial glycation reaction. The intermediate products are known, variously, as Amadori, Schiff base and Maillard products, named after the researchers who first described them. The literature is imprecise in usages of these terms. For example, Maillard reaction products are sometimes considered an intermediate step and other times as AGEs. Side products generated in the intermediate steps may be oxidizing agents such as hydrogen peroxide, and others, such as beta amyloid proteins. Glycosylation is also sometimes used as a synonym for glycation in the literature, but is then usually referred to as 'non-enzymatic glycosylation.'
AGEs may be less, or more, reactive than the initial sugars they were formed from. Foods may be up to 200 times more immunoreactive after cooking. Many cells in the body (for example endothelial cells, smooth muscle or cells of the immune system) from tissue such as lung, liver, kidney or peripheral blood bear the Receptor for Advanced Glycation Endproducts (RAGE) that, when binding AGEs, contributes to age- and diabetes-related chronic inflammatory diseases such as atherosclerosis, asthma, arthritis, myocardial infarction, nephropathy, retinopathy or neuropathy. There may be some chemicals, such as aminoguanidine, that limit the formation of AGEs.
The total state of oxidative and peroxidative stress on the body, and the accumulation of AGE-related damage is proportional to the dietary intake of exogenous (preformed) AGEs, the consumption of highly glycation forming sugars such as fructose and galactose and other factors. Other such factors include diabetes, which increases the average blood sugar level (hyperglycemia) and subsequent kidney damage reduces the effectiveness of the kidney's removal of AGEs, forming a positive feedback loop and further increasing the rate of damage.
AGEs affect nearly every type of cell and molecule in the body, are thought to be major factors in aging and age related chronic diseases. They are also believed to play a causative role in the vascular complications of diabetes mellitus.
AGE's are the subject of ongoing research. AGE crosslink breaking drugs are currently being developed for the purpose breaking crosslinks between proteins. Alt-711, developed by Alteon Corporation is the first of these to reach clinical trials.
Examples of AGE modified sites are carboxymethyllysine (CML), carboxyethyllysine (CEL) and Argpyrimidine which is the most common epitope.
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