Glyoxal Mode of action

glyoxal mode of action

Glyoxal, which attacks amino groups of proteins, nucleotides, and lipids, is considered an important intermediate in the formation of AGEs. AGE modification alters protein function and inactivates enzymes, resulting in disturbance of cellular metabolism, impaired proteolysis, and inhibition of cell proliferation and protein synthesis. The extent of AGE modification increases with the increasing life span of proteins. Consequently, AGEs are especially associated with long-lived proteins, such as collagens, lens crystallins, and neurofilaments, but also have been identified in shorter-lived proteins, including haemoglobin, plasma proteins, lipoproteins, and intracellular proteins. AGEs have a role in the pathogenesis or progression of many pathological conditions — e.g., diabetes, Alzheimer’s disease and other neurodegenerative diseases, chronic inflammatory diseases, arthritis, atherosclerosis, vascular damage, cataract formation and skin changes during ageing, pulmonary fibrosis, and renal failure — as well as in peritoneal dialysis complications. Although glyoxal is known to be an intermediate in the formation of AGEs, these effects have not specifically been shown for glyoxal.

glyoxal structure

Inhibition studies in bacterial mutagenicity tests demonstrated the production of the reactive oxygen species superoxide, hydrogen peroxide, and singlet oxygen from glyoxal. The mutagenic activity of glyoxal is related to singlet oxygen, as well as to the intracellular GSH level. The hydroxyl radical plays a prominent role in glyoxal-induced DNA cleavage.

The sensitizing potential of glyoxal is attributed to the electron-deficient alpha,beta-dicarbonyl structure with its high electrophilic reactivity. Glyoxal easily forms Schiff bases with lysine or arginine units and so becomes bound to skin proteins.

 

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