title: Roles of phosphate and an enoyl radical in ferritin iron mobilization by 5-aminolevulinic acid.
abstract: 5-Aminolevulinic acid (ALA), a heme precursor that accumulates in acute intermittent porphyria (AIP) and lead poisoning, undergoes enolization and subsequent iron-catalyzed oxidation at neutral pH. Iron is released from horse spleen ferritin (HoSF) by both ALA-generated O(2)(.-) and enoyl radical (ALA(z.rad)), which amplifies the chain of ALA oxidation (autocatalysis). Iron chelators such as EDTA, ATP, but not citrate, and phosphate accelerate this process and ALA-promoted iron release from HoSF is faster in horse spleen isoferritins containing larger amounts of phosphate in the core. ALA (+0.377 V versus standard hydrogen electrode) is less effective in releasing iron from ferritin than are thioglycollic acid, 6-hydroxydopamine, and N,N,N', N'-tetramethyl-p-phenylenediamine. During electrochemical one electron oxidation of ALA in a nitrogen atmosphere, spin trapping experiments with 3,5-dibromo-4-nitrosobenzenesulfonic acid demonstrated the formation of a spin adduct characterized by a six line signal, indicating a secondary carbon-centered radical and attributed to a resonant ALA&z.rad; radical. Iron is also released in such anaerobic electrochemical oxidations of ALA in the presence of ferritin, suggesting that, in addition to O(2)(*-), ALA&z.rad; can promote iron mobilization from ferritin. Hence, ALA&z.rad; may amplify the metal-catalyzed oxidation of ALA, damaging ALA-accumulating cells and possibly contributing to the symptoms of porphyria.
authors: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
authors: M E
authors: ME
authors: Rocha
authors: A M
authors: AM
authors: Ferreira
authors: E J
authors: EJ
authors: Bechara
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000622:Aminolevulinic Acid / Q000737:chemistry*; D005293:Ferritins / Q000737:chemistry*; D005609:Free Radicals; D007501:Iron / Q000737:chemistry*; D007700:Kinetics; D010084:Oxidation-Reduction; D016627:Oxidopamine / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry*; D011199:Potentiometry; D013481:Superoxides / Q000737:chemistry*; D013772:Tetramethylphenylenediamine / Q000737:chemistry; D013864:Thioglycolates / Q000737:chemistry
chemical_list: D005609:Free Radicals; D010710:Phosphates; D013864:Thioglycolates; D013481:Superoxides; D000622:Aminolevulinic Acid; D016627:Oxidopamine; D000255:Adenosine Triphosphate; D005293:Ferritins; D007501:Iron; D013772:Tetramethylphenylenediamine