What is Glycation? Part 1 of 5

What is Glycation?

There are many chemical reactions in the body that influence how it functions from the molecular to the cellular level, explaining how tissues, organs and systems work. At the same time, there are natural chemical reactions that occur in the body that explain how certain pathological processes evolve over time. These biochemical reactions include glycosylation and glycation.

Glycosylation versus Glycation

Glycosylation is the chemical reaction in which a simple sugar (carbohydrate) molecule is attached to a  another molecule such as a protein, lipid, or other molecules like nucleic acids. This process is catalyzed by enzymes and results in the formation of various glycans, which are involved in many functional and structural roles in the cells. The important thing to remember here is that these proceses are enzyme-directed chemical reactions which are necessary for normal body functions.

On the other hand, glycation is a chemical reaction which involves attaching sugar molecules to proteins without the help of enzymes. These processes usually disrupt normal metabolic processes and are usually associated with oxidative damage, which result in accelerated aging and other pathological conditions such as diabetes and heart disease.

Simple sugars like glucose and fructose play an important role as reducing sugars in the glycation process. These sugar molecules can become attached to proteins, nucleic acids or lipids, forming unstable compounds called  Schiff base over a few hours. Over weeks, these compounds rearrange to become more stable compounds called Amadori products. Fortunately, these initial reactions are reversible, depending on the available reactants present in the blood. A decrease in blood glucose level, for example, will unhook the sugar molecules from the protein molecules to which they are attached. On the other hand, persistently high glucose levels will have the opposite effect. Therefore, over months, an increase in Amadori products will lead to irreversible formation of other highly stable substances called advanced glycation end products (AGEs) after a series of chemical reactions such as oxidation and degradation.

AGEs normally form at slow but constant rates in the body even before birth, accumulating with time. With an increase in glucose concentration in the blood, however, glycation processes can accelerate AGE formation, leading to premature aging and development of various chronic conditions such as diabetes and its complications.

What are AGEs?

AGEs or advanced glycation end products are destructive molecules that can undergo extensive cross-linking with other protein molecules to form stable chemical bridges. Although the body normally undergoes glycation reactions, these chemical processes may be accelerated in the presence of certain factors, such as a high carbohydrate diet, thus increasing the amount of destructive AGEs in the body. Endogenous AGEs are the result of normal glycation processes which are similar to other chemical processes that occur outside the body, called the Maillard reaction. The Maillard reaction was first described by a French chemist who observed how sugar reacts with fat or protein when exposed to high temperatures, leading to browning of foods while cooking. When food, which is high in protein and fat, is combined with carbohydrates and exposed to heat in the absence of moisture, it turns brown (and delicious) but it may also contain exogenous AGEs and carcinogens (cancer-causing substances) such as 2-propenamide.

AGEs formed outside the body (exogenous AGEs) may also affect an individual. Tobacco smoke is a well-known source of exogenous AGEs. Studies show that diabetic patients who smoke exhibit increased AGE deposition in their eye lenses and arteries. Recent studies also show that the diet is a significant source of  AGEs. Fatty foods cooked in high temperatures and food processing have significant accelerating effects in generating synthetic AGEs. Studies conducted in animals  demonstrate an important link between high intake of dietary AGE and the development of tissue damage related to diabetes, which has been shown to be  prevented by restricted dietary AGE intake.

How AGEs Affect the Body

AGEs crosslink with various proteins inside as well as outside the cells, thus altering mechanical properties and functions of various tissues in the body. AGEs are also capable to modulating many cellular processes which can lead to chronic inflammation, aging and disease. Scientific evidence indicates that glycation may be promoted by oxidative stress and can lead to the production of free radicals, which are associated with aging and chronic disease.

AGEs that have been identified fall into three groups called  N-carboxymethyllysine (CML), pentosidine, and  imidazolium dilysine cross-links. Of these, CML is the most abundant. Increased serum levels of these AGEs, particularly CML and pentosidine are associated with diabetes, coronary heart disease, and other chronic conditions. AGEs may also attach themselves to other structures such as collagen, causing damage to the skin, leading to signs of aging such as wrinkles. Pentosdine has been found in various tissues,  including the trachea, bone, cardiac muscle, aorta, lung, kidney, liver, eye lens, and red blood cells.

Research suggests that AGEs are involved in almost all complications of diabetes, which are conventionally grouped into macro- or microangiopathies or conditions affecting large and small diameter blood vessels of various organs. AGEs can therefore lead to diabetes complications such as retinopathy (involving the eye), nephropathy (kidney disease) and atherosclerosis (arterial stiffness).

Can Glycation be Prevented?

Glycation is one of the normal body processes that is often accelerated by consuming baked food products, fried foods, fatty meat, and other foods cooked and browned in high heat. Studies suggest that foods high in fructose can induce glycation ten times more than glucose. By avoiding these foods, it is believed that advanced glycation may be reduced. Certain foods, however, are believed to prevent glycation, such as fruits and vegetables, green tea, legumes, salmon and oatmeal.

Pharmacologic inhibitors of advanced glycation reactions include aminoguanadine, which has been found to prevent the development of complications of diabetes in animal studies. Aminoguanadine appears to work by preventing the conversion of Amadori products to AGEs, thus inhibiting cross linking.

Next article we are going to discuss  Glycation and Mitochondrial Dysfunction.


Hegab Z, Gibbons S, Mamas M, et al. Role of advanced glycation end products in cardiovascular disease. World J Cardiol. 2012 Apr; 4 (4): 20-102. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342583/

Peppa M, Uribarri J, and Vlassara H. Glucose, Advanced Glycation End Products, and Diabetes Complications: What Is New and What Works. Clinical Diabetes October 2003 vol. 21 no. 4 186-187.


Hatfield, J. REVIEW: Advanced Glycation End-products (AGEs) in Hyperglycemic Patients. Journal of Young Investigators. http://www.jyi.org/issue/review-advanced-glycation-end-products-ages-in-hyperglycemic-patients/

Shaw, G. Is Your Diet Aging You? WebMD. http://www.webmd.com/diet/features/is-your-diet-aging-you.


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