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Methionine regulates copper/hydrogen peroxide oxidation products of Aβ
Author(s) -
Ali Feda E.,
Separovic Frances,
Barrow Colin J.,
Cherny Robert A.,
Fraser Fiona,
Bush Ashley I.,
Masters Colin L.,
Barnham Kevin J.
Publication year - 2005
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.626
Subject(s) - hydrogen peroxide , copper , chemistry , methionine , biochemistry , combinatorial chemistry , organic chemistry , amino acid
Metal‐catalysed oxidation (MCO) may play a causative role in the pathogenesis of Alzheimer's disease (AD). Amyloid β peptide (Aβ), 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. Aβ 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 Aβ, 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 Aβ (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 Aβ and may relate to changes in properties of the peptide following MCO. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.