title: Methionine regulates copper/hydrogen peroxide oxidation products of Abeta.
abstract: Metal-catalysed oxidation (MCO) may play a causative role in the pathogenesis of Alzheimer's disease (AD). Amyloid beta peptide (Abeta), the major biomarker of AD, in the presence of copper ions reduces Cu(2+) to Cu(+) and catalyses the formation of H(2)O(2) that subsequently induces radicals through Fenton chemistry. Abeta is also subject to attack by free radicals, where the presence of Cu(2+) in conjunction with H(2)O(2) catalyses oxygenation, primarily at the methionine sulfur atom. This work investigates MCO of Abeta, to gain further insight into the role of oxidative stress in AD. By combining a fluorescence assay with gel electrophoresis to monitor MCO reactions of Abeta (1-28) in the presence and absence of methionine it was determined that methionine can both protect some residues against MCO and promote the oxidation of Tyr(10) specifically. Electrospray ionization mass spectrometric analysis of methionine MCO products indicated the formation of methionine sulfoxide, methionine sulfone and related hydroxylated products. Similar products could be formed from the oxidation of Met(35) of Abeta and may relate to changes in properties of the peptide following MCO.
authors.affiliation: School of Chemistry, University of Melbourne, VIC 3010, Australia.
authors.forename: Feda E
authors.initials: FE
authors.lastname: Ali
authors.forename: Frances
authors.initials: F
authors.lastname: Separovic
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Barrow
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cherny
authors.forename: Fiona
authors.initials: F
authors.lastname: Fraser
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Barnham
mesh_terms: D000544:Alzheimer Disease; D000596:Amino Acids / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D003300:Copper / Q000494:pharmacology*; D006735:Horseradish Peroxidase; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008715:Methionine / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000596:Amino Acids; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D003300:Copper; D008715:Methionine; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase