Acetyl radical production by the methylglyoxal-peroxynitrite system: a possible route for L-lysine acetylation.

Methylglyoxal is an α-oxoaldehyde putatively produced in excess from triose phosphates, aminoacetone, and acetone in some disorders, particularly in diabetes. Here, we investigate the nucleophilic addition of ONOO−, known as a potent oxidant and nucleophile, to methylglyoxal, yielding an acetyl radical intermediate and ultimately formate and acetate ions. The rate of ONOO− decay in the presence of methylglyoxal [k2,app = (1.0 ± 0.1) × 103 M−1 s−1; k2 ≈ 1.0 × 105 M−1 s−1] at pH 7.2 and 25 °C was found to be faster than that reported with monocarbonyl substrates (k2 < 103 M−1 s−1), diacetyl (k2 = 1.0 × 104 M−1 s−1), or CO2 (k2 = 3−6 × 104 M−1 s−1). The pH profile of the methylglyoxal−peroxynitrite reaction describes an ascendant curve with an inflection around pH 7.2, which roughly coincides with the pKa values of both ONOOH and H2PO4− ion. Electron paramagnetic resonance spin trapping experiments with 2-methyl-2-nitrosopropane revealed concentration-dependent formation of an adduct that can be attributed t...