Medical Wikipedia : The Medical Encyclopedia
Advanced Glycation End Products
ADVANCED GLYCATION END PRODUCTS
Proteins or lipids become glycated as a result of exposure to
sugars. This is commonly seen in the matrix of the cells.
Advanced Glycation End Products (AGEs) act as biomarkers. AGEs are implicated
in chronic degenerative diseases like diabetes mellitus, atherosclerosis, chronic
kidney disease and Alzheimer’s disease.
The protein (Lysine residues usually) reacts with the reducing sugar to give a N-
substituted glycosylamine and water. This is a spontaneous, non-enzymatic
reaction called Maillard Reaction. It is a reversible reaction.
The N-substituted glycosylamine then undergoes Amadori rearrangement to
give Ketosamines. The formation of Ketosamines are irreversible.
Mechanism of action
1. AGEs affect nearly every cell in the body and are believed to play an
important role in aging. AGEs can link to any type of proteins and form
stable and irreversible bonds. Their bioavailability depends on the half-
life time of those proteins.
2. Cross-linking of collagen proteins contributes to the rigidity and loss of
elasticity of tissues and increased resistance to proteolysis, inhibition of
tissue remodeling and thickening of capillary basement membrane
leading to widespread alterations. This also affects vessel wall elasticity.
3. AGEs exert their effects via receptors, with a proven pathogenic
significance, as they mediate cellular responses through the generation
of oxygen-free radicals. This leads to induction of Oxygen Stress, which is
believed to mediate the chronic complications of Diabetes Mellitus and
Chronic Kidney disease.
Skin collagen and lens have a very long half-life so these places are the most likely
sites for AGEs accumulation. Bonds to other types of proteins with shorter
half-lives are unstable.So these bonds lead to AGEs degradation followed by renal
excretion of AGEs-moieties. The accumulation of AGEs in skin collagen and
lens bring about the degenerative changes with aging, i.e, wrinkling of skin
and progressive worsening of eyesight.
2. Heart failure
AGEs affect the heart by two different pathways:
Interference with matrix proteins of coronary arteries causing
atherosclerosis and Interaction with RAGE (AGE specific receptors) to bring
about metabolic alterations in the myocardium and inflammatory
responses in the vascular endothelium on top of oxidative stress, leading to
3. Diabetes Mellitus
Increased AGEs mediate the long term complications of diabetes mellitus
such as atherosclerosis and cataract formation. Atherosclerosis occurs due
to deposition of AGEs in the vessel wall which leads to deposition of plasma
proteins and LDL particles in the vessel wall, progressing to atherosclerosis.
The rate of formation of AGEs in diabetes is said to be proportional to the
square of glucose concentration.
4. AGEs also are implicated in other conditions like Alzheimer’s disease and
Questions & Answers
Proteins are usually glycated through which residues
- Glutamic acid
|Proteins are usually glycated through Lysine residues|
Which vitamin is found to inhibit AGE formation in the laboratory
- Vitamin B3
- Vitamin B5
- Vitamin B9
- Vitamin C
|Vitamin C is found to inhibit AGE formation in the laboratory|
All of the following are pathological effects of AGEs EXCEPT
- Decreased vascular permeability
- Increased arterial stiffness
- Inhibition of vascular dilation by interfering with nitric oxide.
- Oxidizing LDL
|AGEs - Increase vascular permeability|