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 structures in the cell which are responsible for generating energy in the form of ATP (adenosine triphosphate).
Research has also shown that accelerated AGE formation and accumulation is characteristic of chronic conditions such as diabetes and heart disease, as well as ageing, renal disease and neurologic degeneration.
Glycation and Diabetes
Diabetes affects more than 200 million people all over the world. The hallmark of this disease is a chronic elevation in blood sugar levels (hyperglycemia), which has been found to accelerate AGE production and accumulation. This continuous production of AGEs causes mitochondrial dysfunction, which leads to the development of various complications of the disease. These include renal complications (diabetic nephropathy), eye complications (diabetic retinopathy), and nerve problems (diabetic neuropathy). Studies show that an increase in AGE levels correlate with the severity of these complications. Furthermore, it has been shown that aminoguanidine, a substance that inhibits AGE formation, can prevent retinopathy in experimental animals that have been induced to develop diabetes. Also, AGEs have been found to accumulate in the peripheral nerves of diabetic patients but treating...