Glycation Explained

Glycation (non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein, lipid or nucleic acid molecule. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic process responsible for many (e.g. micro and macrovascular) complications in diabetes mellitus and is implicated in some diseases and in aging.[1] [2] [3] Glycation end products are believed to play a causative role in the vascular complications of diabetes mellitus.[4]

In contrast with glycation, glycosylation is the enzyme-mediated ATP-dependent attachment of sugars to protein or lipid. Glycosylation occurs at defined sites on the target molecule. It is a common form of post-translational modification of proteins and is required for the functioning of the mature protein.

Biochemistry

Glycations occur mainly in the bloodstream to a small proportion of the absorbed simple sugars: glucose, fructose, and galactose. It appears that fructose has approximately ten times the glycation activity of glucose, the primary body fuel.[5] Glycation can occur through Amadori reactions, Schiff base reactions, and Maillard reactions; which lead to advanced glycation end products (AGEs).

Biomedical implications

Red blood cells have a consistent lifespan of 120 days and are accessible for measurement of glycated hemoglobin. Measurement of HbA1c—the predominant form of glycated hemoglobin—enables medium-term blood sugar control to be monitored in diabetes.

Some glycation products are implicated in many age-related chronic diseases, including cardiovascular diseases (the endothelium, fibrinogen, and collagen are damaged) and Alzheimer's disease (amyloid proteins are side-products of the reactions progressing to AGEs).[6] [7]

Long-lived cells (such as nerves and different types of brain cell), long-lasting proteins (such as crystallins of the lens and cornea), and DNA can sustain substantial glycation over time. Damage by glycation results in stiffening of the collagen in the blood vessel walls, leading to high blood pressure, especially in diabetes.[8] Glycations also cause weakening of the collagen in the blood vessel walls,[9] which may lead to micro- or macro-aneurysm; this may cause strokes if in the brain.

DNA glycation

The term DNA glycation applies to DNA damage induced by reactive carbonyls (principally methylglyoxal and glyoxal) that are present in cells as by-products of sugar metabolism.[10] Glycation of DNA can cause mutation, breaks in DNA and cytotoxicity.[10] Guanine in DNA is the base most susceptible to glycation. Glycated DNA, as a form of damage, appears to be as frequent as the more well studied oxidative DNA damage. A protein, designated DJ-1 (also known as PARK7), is employed in the repair of glycated DNA bases in humans, and homologs of this protein have also been identified in bacteria.[10]

See also

Additional reading

Notes and References

  1. Glenn . J.. Stitt . A.. The role of advanced glycation end products in retinal ageing and disease. Biochimica et Biophysica Acta (BBA) - General Subjects. 1790. 10. 1109–1116. 2009. 19409449. 10.1016/j.bbagen.2009.04.016.
  2. 10.1007/BF03325227. 19448391. 2009. Semba . R. D.. Ferrucci. Sun. Beck. Dalal. Varadhan. Walston. Guralnik. Fried. Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community-dwelling women. 21. 2. 182–190. Aging Clinical and Experimental Research . L. . K. . J. . M. . R. . J. . J. M. . L. P.. 2684987.
  3. Semba . R.. Najjar . S.. Sun . K.. Lakatta . E.. Ferrucci . L.. Serum carboxymethyl-lysine, an advanced glycation end product, is associated with increased aortic pulse wave velocity in adults. American Journal of Hypertension. 22. 1. 74–79. 2009. 19023277. 10.1038/ajh.2008.320. 2637811.
  4. 18331228. 2007. Yan . S. F.. D'Agati. Schmidt. Ramasamy. Receptor for Advanced Glycation Endproducts (RAGE): a formidable force in the pathogenesis of the cardiovascular complications of diabetes & aging. 7. 8. 699–710. Current Molecular Medicine. 10.2174/156652407783220732 . V. . A. M. . R..
  5. 10.1021/bi00406a016 . McPherson JD, Shilton BH, Walton DJ . Role of fructose in glycation and cross-linking of proteins . Biochemistry . 27 . 6 . 1901–7 . March 1988 . 3132203.
  6. Münch. Gerald. Influence of advanced glycation end-products and AGE-inhibitors on nucleation-dependent polymerization of β-amyloid peptide. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 27 February 1997. 1360. 1. 17–29. 10.1016/S0925-4439(96)00062-2. 9061036. etal.
  7. Munch. G. Deuther-Conrad W . Gasic-Milenkovic J. . Glycoxidative stress creates a vicious cycle of neurodegeneration in Alzheimer's disease--a target for neuroprotective treatment strategies?. J Neural Transm Suppl. 2002. 62. 303–307. 12456073. 62. 10.1007/978-3-7091-6139-5_28.
  8. Soldatos. G.. Cooper ME. Advanced glycation end products and vascular structure and function. Curr Hypertens Rep. Dec 2006. 8. 6. 472–478. 17087858. 10.1007/s11906-006-0025-8. 31239347.
  9. Lee. J. Michael. Samuel P. Veres. Advanced glycation end-product cross-linking inhibits biomechanical plasticity and characteristic failure morphology of native tendon. Journal of Applied Physiology. 2019-04-02. 126. 4. 832–841. 10.1152/japplphysiol.00430.2018. 30653412. 6485690.
  10. Richarme G, Liu C, Mihoub M, Abdallah J, Leger T, Joly N, Liebart JC, Jurkunas UV, Nadal M, Bouloc P, Dairou J, Lamouri A. Guanine glycation repair by DJ-1/Park7 and its bacterial homologs. Science. 2017 Jul 14;357(6347):208-211. doi: 10.1126/science.aag1095. Epub 2017 Jun 8. PMID 28596309

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