The Role of Advanced Glycation End Products in Diabetes and Heart Disease

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Glycation is a natural chemical reaction in the body that involves combining sugar molecules to protein molecules without the help of enzymes. In contrast to similar a chemical reaction that involves enzyme-directed processes called glycosylation, glycation disrupts normal metabolic pathways. This results in the production of advanced glycation end products (AGEs), which are assocated with oxidative damage that leads to pathological changes in various organ systems.

AGEs and Chronic Disease

The 'normal' American diet usually contains a lot of high-sugar, high-fat foods that have been associated with the development of chronic diseases such as diabetes and heart disease. Just how these processes come about can be explained in the molecular and cellular level by the formation of AGEs.

Simple sugars such as glucose and fructose that are usually derived from a sugar-rich diet become attached to nucleic acids and protein molecules to form unstable compounds that eventually accumulate to become destructive, more stable compounds called AGEs. Although AGEs are known to be produced by the body at slow, but constant rates from birth, the process can accelerate with increased consumption of sugars as well as decreased metabolism of these substances.

AGEs alter the mechanical properties of cells and tissues by crosslinking intracellular and extracellular proteins. They also bind to cell surface receptors called receptor for AGEs (RAGE), thus interrupting various cellular processes. Through laboratory experiments, scientists have shown that glycation of mitochondrial proteins, lipids and DNA may induce mitochondrial dysfunction due to a decrease in ATP production and increased free radical formation. The mitochondria are specialized...

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