Glycation is the result of a reducing sugar molecule, such as fructose or glucose, bonding to a protein or lipid molecule without the controlling action of an enzyme. It may occur either in the body (endogenous) or outside the body (exogenous). Enzyme-controlled addition of carbohydrates is termed glycosylation; this process is less haphazard than glycation. Much early laboratory research work on fructose glycations used inaccurate assay techniques that drastically understated its importance in glycation formation (Ahmed & Furth 1992)

Exogenous

Exogenous glycations are typically formed when sugars are cooked with proteins or fats at temperatures over 120 C (~248 F). These compounds are absorbed by the body during digestion with about 35% efficiency. Browning reactions (usually Maillard type reactions)are evidence of pre-formed glycations. Indeed, sugar is often added to products such as french fries and baked goods to enhance browning. Glycation may also contribute to the formation of acrylamide (Stadler et al 2002), a potential carcinogen, during cooking.

Endogenous

Endogenous glycations occur mainly in the bloodstream to a small proportion of the absorbed simple sugars: glucose, fructose and galactose. The balance of the sugar molecules are used for metabolic processes. It appears that fructose and galactose have approximately ten times the glycation activity of glucose, the primary body fuel (McPherson et al 1988). Glycation is the first step in the evolution of these molecules through a complex series of very slow reactions in the body known as Amadori reactions , Schiff base reactions , and Maillard reactions; all lead to advanced glycation endproducts (AGEs). Some AGEs are benign, but others are more reactive than the sugars they are derived from, and are implicated in many age-related chronic diseases such as: type II diabetes mellitus (beta cell damage), cardiovascular diseases (the endothelium and collagen are damaged), Alzheimer's disease (amyloid proteins are side products of the reactions progressing to AGEs), cancer (acrylamide and other side products are released), peripheral neuropathy (the myelin is attacked), and other sensory losses such as deafness (due to demyelination) and blindness (mostly due to microvascular damage in the retina). This range of diseases is the result of the very basic level at which glycations interfere with molecular and cellular functioning throughout the body and the release of highly oxidizing side products such as hydrogen peroxide.

Glycated substances are eliminated from the body slowly, since the renal clearance factor is only about 30%. This implies that the half life of a glycation within the body is about double the average cell life. Red blood cells are the shortest lived cells in the body (120 days), so, the half life is about 240 days. This fact is used in monitoring blood sugar control in diabetes by monitoring the glycated hemoglobin (GHb)level. Consequently, long lived cells (such as nerves, brain cells, eye crystalline cells, and collagen) may accumulate substantial damage over time. Metabolically active cells such as the glomeruli in the kidneys, retina cells in the eyes, and beta cells (insulin producing) in the pancreas are also at high risk of damage. The epithelial cells of the blood vessels are damaged directly by glycations, which are implicated in atherosclerosis, for example. Damage by glycation results in stiffening of the collagen in the blood vessel walls leading to high blood pressure. Glycations also cause weakening of the collagen in the blood vessel walls, which may lead to micro- or macro aneurisms; this may cause strokes if in the brain.

References

• Ahmed N, Furth AJ. Failure of common glycation assays to detect glycation by fructose. Clin Chem 1992;38:1301-3 PMID 1623595.
• McPherson JD, Shilton BH, Walton DJ. Role of fructose in glycation and cross-linking of proteins. Biochemistry 1988;27:1901-7. PMID 3132203.
• Stadler RH, Blank I, Varga N, Robert F, Hau J, Guy PA, Robert MC, Riediker S. Acrylamide from Maillard reaction products. Nature 2002;419:449-50. PMID 12368845.