title: Ferricytochrome (c) directly oxidizes aminoacetone to methylglyoxal, a catabolite accumulated in carbonyl stress.
abstract: 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.
authors.affiliation: Departamento de Bioquímica, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Adriano
authors.initials: A
authors.lastname: Sartori
authors.forename: Camila M
authors.initials: CM
authors.lastname: Mano
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Mantovani
authors.forename: Fábio H
authors.initials: FH
authors.lastname: Dyszy
authors.forename: Júlio
authors.initials: J
authors.lastname: Massari
authors.forename: Rita
authors.initials: R
authors.lastname: Tokikawa
authors.forename: Otaciro R
authors.initials: OR
authors.lastname: Nascimento
authors.forename: Iseli L
authors.initials: IL
authors.lastname: Nantes
authors.forename: Etelvino J H
authors.initials: EJ
authors.lastname: Bechara
mesh_terms: D000096:Acetone / Q000031:analogs & derivatives* / Q000378:metabolism; D000332:Aerobiosis / Q000187:drug effects; D000818:Animals; D002384:Catalysis / Q000187:drug effects; D002942:Circular Dichroism; D003198:Computer Simulation; D003300:Copper / Q000494:pharmacology; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006736:Horses; D007477:Ions; D007501:Iron / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D011765:Pyruvaldehyde / Q000378:metabolism*; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013312:Stress, Physiological / Q000187:drug effects; D013696:Temperature
chemical_list: D005609:Free Radicals; D007477:Ions; D000096:Acetone; D006418:Heme; D011765:Pyruvaldehyde; D003300:Copper; D045304:Cytochromes c; D007501:Iron; C006495:aminoacetone