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

Excess 5-aminolevulinic acid (ALA) and α-aminoacetone (AA) are implicated in ketosis, porphyrinpathies and diabetes. Pathologic manifestations involve O2−, H2O2, OH, enoyl radicals (ALA and AA) and their oxidation end products. To characterize enoyl radicals resulting from reaction of OH radicals with ALA and AA, micromolar OH concentrations were produced by pulse radiolysis of ALA and AA in aqueous solutions. ALA and AA react with OH at k=1.5×109M−1s−1. At pH7.4, the ALA absorbance spectrum has a maximum at 330nm (ε=750M−1cm−1). This band appears as a shoulder at pH8.3 where two ALA species are present: (NH3)+-CH2-CO-CH2-CH2-COO− and NH2-CH2-CO-CH2-CH2-COO− (pKa=8.3). At pH8.3, ALA reacts with oxygen (k=1.4×108M−1s−1) but not with O2−. At pH8.3, AA oxidation produces two AA species characterized by an absorbance spectrum with maxima at 330 and 450nm. ALA and AA are repaired by antioxidants (quercetin (QH), catechin, trolox, ascorbate) which are semi-oxidized (k>108M−1s−1). QH bound to HSA or to apoferritin and ferritin repairs ALA and AA. In O2-saturated apoferritin solutions, Q, O2−, AA and reaction product(s) react with QH. The optical absorption properties and the time evolution of ALA and AA were established for the first time. These radicals and their reaction products may be neutralized by antioxidants free in solution or bound to proteins. Adjuvant antioxidant administration may be of interest in pathologies related to excess ALA or AA production. •ALA and α-aminoacetone (AA) autooxidation leads to pathologic disturbances.•Enoyl radicals, O2−, H2O2, and OH are produced by this autooxidation.•ALA and AA are oxidized by OH at a rate of 1.5×109M−1s−1 with enoyl radical formation.•Enoyl radicals readily react with O2 but not with O2−.•Enoyl radicals and end products are neutralized by free or protein-bound antioxidants.