title: Chemistry of free radicals produced by oxidation of endogenous α-aminoketones. A study of 5-aminolevulinic acid and α-aminoacetone by fast kinetics spectroscopy.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  ALA and AA react with OH at k=1.5 × 10⁹ M⁻¹s⁻¹. At pH7.4, the ALA absorbance spectrum has a maximum at 330 nm (ε=750 M⁻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 × 10⁸ M⁻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 450 nm. ALA and AA are repaired by antioxidants (quercetin (QH), catechin, trolox, ascorbate) which are semi-oxidized (k>10(8)M⁻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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  Adjuvant antioxidant administration may be of interest in pathologies related to excess ALA or AA production.
authors.affiliation: INSERM, U1088, 80054 Amiens, France; CHU Amiens, Pôle Biologie, Pharmacie et Santé des Populations, Centre de Biologie Humaine, Laboratoire de Biochimie, 80054 Amiens, France; Université de Picardie Jules Verne, UFR de Pharmacie, 80036 Amiens, France. Electronic address: morliere.patrice@chu-amiens.fr.
authors.forename: P
authors.initials: P
authors.lastname: Morlière
authors.affiliation: University of Notre Dame, Radiation Laboratory, Notre Dame, IN 46556, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Hug
authors.affiliation: CHU Amiens, Pôle Biologie, Pharmacie et Santé des Populations, Centre de Biologie Humaine, Laboratoire de Biochimie, 80054 Amiens, France; University of Notre Dame, Radiation Laboratory, Notre Dame, IN 46556, USA.
authors.forename: L K
authors.initials: LK
authors.lastname: Patterson
authors.affiliation: INSERM, U1088, 80054 Amiens, France; CHU Amiens, Pôle Biologie, Pharmacie et Santé des Populations, Centre de Biologie Humaine, Laboratoire de Biochimie, 80054 Amiens, France; Université de Picardie Jules Verne, UFR de Médecine, 80036 Amiens, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Mazière
authors.affiliation: INSERM, U1088, 80054 Amiens, France; CHU Amiens, Pôle Biologie, Pharmacie et Santé des Populations, Centre de Biologie Humaine, Laboratoire de Biochimie, 80054 Amiens, France; Université de Picardie Jules Verne, UFR de Médecine, 80036 Amiens, France.
authors.forename: J
authors.initials: J
authors.lastname: Ausseil
authors.affiliation: Université de Picardie Jules Verne, UFR de Médecine, 80036 Amiens, France; CHU Amiens, Service d'Hépato-Gastroentérologie, 80054 Amiens, France.
authors.forename: J-L
authors.initials: JL
authors.lastname: Dupas
authors.affiliation: Université de Picardie Jules Verne, UFR de Médecine, 80036 Amiens, France; CHU Amiens, Service de Médecine Interne et Maladies Systémiques, 80054 Amiens, France.
authors.forename: J-P
authors.initials: JP
authors.lastname: Ducroix
authors.affiliation: CHU Amiens, Pôle Biologie, Pharmacie et Santé des Populations, Centre de Biologie Humaine, Laboratoire de Biochimie, 80054 Amiens, France; Muséum National d'Histoire Naturelle, Département RDDM, 75231 Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Santus
authors.affiliation: Hospital de Santa Maria, Faculdade de Medicina de Lisboa, Clínica Dermatologica Universitaria and Unidade de Investigação em Dermatologia, Instituto de Medicina Molecular, 1699 Lisboa Codex, Portugal.
authors.forename: P
authors.initials: P
authors.lastname: Filipe
mesh_terms: D000096:Acetone / Q000031:analogs & derivatives* / Q000737:chemistry; D000622:Aminolevulinic Acid / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry*; D010084:Oxidation-Reduction; D013057:Spectrum Analysis
chemical_list: D005609:Free Radicals; D000096:Acetone; D000622:Aminolevulinic Acid; C006495:aminoacetone
keywords: 5-Aminolevulinic acid; Antioxidants; Horse spleen ferritin; Human serum albumin; Pulse radiolysis; α-Aminoacetone