Archives of Clinical and Biomedical Research

ISSN: 2572-5017
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Biochemistry and Pathophysiology of Glycation of DNA: Implications in Diabetes

Advanced glycated end products (AGEs) are molecules formed from the non-enzymatic reaction of reducing sugar with free amino group of proteins, lipids and nucleic acids. The AGEs play crucial role in the pathogenesis of cardiovascular, kidney, Alzheimer’s, neurological, diabetes and joints diseases and aging process. Depletion of cellular antioxidant GSH led to increase binding of glucose derivatives to DNA. DNA can be cross-linked with different substances, some of the nucleotide AGEs are N2-carboxymethyl oxyguanosine, 5-glycolyl deoxycytidine etc. Glycation of DNA evolves from the formation of Amadori products finally culminating into DNA AGEs. Glycation of DNA yields characteristics type of nucleotide adducts which are indicator of many abnormal conditions such as oxidative stress, arthritis etc. The glyoxal and methyl glyoxals are the earlier form of DNA glycation products which are derived from the reducing carbohydrate compounds. The AGEs and their product associated with the mutation, break down of DNA strand, cytotoxicity and various inflammatory conditions. High concentration of accumulated products observed in diseases like diabetes, uremia, atherosclerosis, asthma, arthritis, myocardial infarction, nephropathy, retinopathy, periodontitis, neuropathy and other inflammatory conditions. The decline rate of DNA repair mechanisms and persistence of DNA lesion with increased age of persons enhance the rate of nucleotide glycation.

Author(s): Rizwan Ahmad, Ashok Kumar Sah and Haseeb Ahsan

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