Free radical generation during delta-aminolevulinic acid autoxidation: induction by hemoglobin and connections with porphyrinpathies.
delta-Aminolevulinic acid (ALA), a heme precursor accumulated in acute intermittent porphyria and saturnism, undergoes autoxidation leading to ammonium ion and probably the corresponding alpha-ketoaldehyde. This reaction is accelerated by addition of oxyhemoglobin (oxyHb) and other iron complexes. OxyHb is concomitantly oxidized to metHb; the apparent second-order rate constant of oxyHb/ALA coupled oxidation is ca. 10 M-1 min-1.1H NMR and uv spectral studies suggest that ALA undergoes enolization before consuming the dissolved oxygen. Spin-trapping experiments demonstrate formation of both the hydroxyl radical and a substrate-derived carbon-centered radical during ALA oxidation. Generation of active oxygen species by ALA might be related to the neuropathy associated to some acquired and inherited porphyrinpathies.
Monteiro
H P
HP
Instituto de Quimica da USP, Sao Paulo, Brazil.
Abdalla
D S
DS
Augusto
O
O
Bechara
E J
EJ
D000622:Aminolevulinic Acid / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006801:Humans; D007982:Levulinic Acids / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010108:Oxyhemoglobins / Q000494:pharmacology*; D011048:Polarography; D011164:Porphyrias / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
D005609:Free Radicals; D007982:Levulinic Acids; D010108:Oxyhemoglobins; D000622:Aminolevulinic Acid