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.

Methylglyoxal in Metabolic Disorders: Facts, Myths, and Promises

“…MG is a highly reactive dicarbonyl aldehyde that is produced mainly during the glycolysis from fructose (through aldolase B catalysis), glyceraldeyde‐3‐P, dihydroxyacetone, and aminoacetone (through semicarbazide‐sensitive amine oxidase or ferricytochrome C catalysis; Fig. ) . Fructose accumulation in models of metabolic syndrome and diet supplementation leads to increased MG formation, which is prevented by aldolase B knockout .…”

l‐Tryptophan Interactions with the Horseradish Peroxidase‐Catalyzed Generation of Triplet Acetone

“…The IBAL/HRP system can also be employed as a model for the molecular elucidation of human "carbonyl stress," since a large collection of metabolites-alkanals, alkenals, α-dicarbonyls, β-ketoacids, α-hydroxyand α-aminoketones, among others, have been shown in vitro, in cell cultures and in experimental animals to be endowed with the potential to produce triplet species, as well as to attach to proteins and nucleic acids (24,46). It should be pointed out that Trp and other redox-active amino acids such as His, Lys, Tyr, Cys and Met can interfere in enzymatic redox cycles through electronic excitation and electron transfer mechanisms.…”

Chemistry of free radicals produced by oxidation of endogenous α-aminoketones. A study of 5-aminolevulinic acid and α-aminoacetone by fast kinetics spectroscopy

“…Ferritin --an essential protein responsible for iron storage in soluble and non-toxic form [28] --has been shown to be quite sensitive to harmful • AK radicals and to produce ROS [3,[14][15][16]. It has recently been demonstrated that QH could partially repair oxidative damage inflicted to residues of apoFt or Ft [29].…”

“…• ALA and• AA radicals have been implicated in pathological processes[3,[14][15][16]. It is therefore of interest to determine whether effective neutralization of • AK radicals by good electrons or hydrogen donors like antioxidants may be possible.…”