glycation

Definition: Glycation (sometimes called non-enzymatic glycosylation) is the result of a sugar molecule, such as fructose or glucose, bonding to a protein or lipid molecule without the controlling action of an enzyme. All blood sugars are reducing molecules.

See also : AGEs : advanced glycation end-product

Glycation may occur either inside the body (endogenous glycation) or outside the body (exogenous glycation).

Enzyme-controlled addition of sugars to protein or lipid molecules is termed glycosylation; glycation is a haphazard process that impairs the functioning of biomolecules, whereas glycosylation occurs at defined sites on the target molecule and is required in order for the molecule to function.

Much of the early laboratory research work on fructose glycations used inaccurate assay techniques that led to drastic underestimation of the importance of fructose in glycation

Endogenous glycation

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 is used for metabolic processes. It appears that fructose and galactose have approximately ten times the glycation activity of glucose, the primary body fuel.

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 I and II diabetes mellitus (beta cell damage), cardiovascular diseases (the endothelium, fibrinogen, 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 have a consistent lifespan of 120 days and are easily accessible for measurement of recent increased presence of glycating prdouct. This fact is used in monitoring blood sugar control in diabetes by monitoring the glycated hemoglobin level, also known as HbA1c.

As a consequence, long-lived cells (such as nerves, brain cells), long-lasting proteins (such as eye crystalline and collagen), and DNA 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 endothelial cells of the blood vessels are damaged directly by glycations, which are implicated in atherosclerosis, for example.

Atherosclerotic plaque tends to accumulate at areas of high blood flow (such as the entrance to the coronary arteries) due to the increased presentation of sugar molecules, glycations and glycation end-products at these points. 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.