Ferricytochrome (c) directly oxidizes aminoacetone to methylglyoxal, a catabolite accumulated in carbonyl stress

• Published in: PloS one Vol. 8; no. 3; p. e57790
• Main Authors: Sartori, Adriano, Mano, Camila M, Mantovani, Mariana C, Dyszy, Fábio H, Massari, Júlio, Tokikawa, Rita, Nascimento, Otaciro R, Nantes, Iseli L, Bechara, Etelvino J H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science (PLoS) 2013
• Subjects: Acetone - analogs & derivatives; Acetone - metabolism; Aerobiosis - drug effects; Animals; Catalysis - drug effects; Circular Dichroism; Computer Simulation; Copper - pharmacology; Cytochromes c - chemistry; Cytochromes c - metabolism; Electron Spin Resonance Spectroscopy; Free Radicals - metabolism; Heme - metabolism; Horses; Ions; Iron - pharmacology; Oxidation-Reduction - drug effects; Oxygen Consumption - drug effects; Protein Carbonylation - drug effects; Pyruvaldehyde - metabolism; Rats; Spectrophotometry, Ultraviolet; Stress, Physiological - drug effects; Temperature
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0057790

Age-related diseases are associated with increased production of reactive oxygen and carbonyl species such as methylglyoxal. Aminoacetone, a putative threonine catabolite, is reportedly known to undergo metal-catalyzed oxidation to methylglyoxal, NH4(+) ion, and H2O2 coupled with (i) permeabilization of rat liver mitochondria, and (ii) apoptosis of insulin-producing cells. Oxidation of aminoacetone to methylglyoxal is now shown to be accelerated by ferricytochrome c, a reaction initiated by one-electron reduction of ferricytochrome c by aminoacetone without amino acid modifications. The participation of O2(•-) and HO (•) radical intermediates is demonstrated by the inhibitory effect of added superoxide dismutase and Electron Paramagnetic Resonance spin-trapping experiments with 5,5'-dimethyl-1-pyrroline-N-oxide. We hypothesize that two consecutive one-electron transfers from aminoacetone (E0 values = -0.51 and -1.0 V) to ferricytochrome c (E0 = 0.26 V) may lead to aminoacetone enoyl radical and, subsequently, imine aminoacetone, whose hydrolysis yields methylglyoxal and NH4(+) ion. In the presence of oxygen, aminoacetone enoyl and O2(•-) radicals propagate aminoacetone oxidation to methylglyoxal and H2O2. These data endorse the hypothesis that aminoacetone, putatively accumulated in diabetes, may directly reduce ferricyt c yielding methylglyoxal and free radicals, thereby triggering redox imbalance and adverse mitochondrial responses.