Review
Pharmacology of methylglyoxal: formation, modification of proteins and nucleic acids, and enzymatic detoxification-A role in pathogenesis and antiproliferative chemotherapy

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Abstract

  • 1.

    1. Methylglyoxal is a reactive α-oxoaldehyde and physiological metabolite formed by the fragmentation of triose-phosphates, and by the metabolism of acetone and aminoacetone.

  • 2.

    2. Methylglyoxal modifies guanylate residues to form 6,7-dihydro-6,7-dihydroxy-6-methyl-imidazo[2,3-b]purine-9(8)one and N2-(1-carboxyethyl)guanylate residues and induces apoptosis.

  • 3.

    3. Methylglyoxal modifies arginine residues in proteins to form Nδ-(4,5-dihydroxy-4-methylimidazolidin-2-yl) ornithine, Nδ-(5-hydro-5-methylimidazol-4-on-2-yl)ornithine and Nδ-(5)methylimida-zol-4-on-2-yl)ornithine residues.

  • 4.

    4. Methylglyoxal-modified proteins undergo receptor-mediated endocytosis and lysosomal degradation in monocytes and macrophages, and induce cytokine synthesis and secretion.

  • 5.

    5. Methylglyoxal is detoxified by the glyoxalase system. Decreased detoxification of methylglyoxal may be induced pharmacologically by glyoxalase I inhibitors which have anti-tumor and anti-malarial activities.

  • 6.

    6. The modification of nucleic acids and protein by methylglyoxal is a signal for their degradation and may have a role in the development of diabetic complications, atherosclerosis, the immune response in starvation, aging and oxidative stress.

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