Cited by 12Redox biology and oxidative stressAntioxidant Activity and Oxidative StressSulfur Compounds in Biology

Methionine oxidation products as biomarkers of oxidative damage to proteins and modulators of cellular metabolism and toxicity

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Davies, Michael J.·2025·Redox Biochemistry and Chemistry

Abstract

Proteins are highly abundant and readily oxidized targets of reactive species formed in biological systems, with these often accounting for greater than 50% of the dry mass of biological samples. Of the amino acids present in proteins, the sulfur-containing amino acids cysteine (Cys), cystine and methionine (Met) are some of the most reactive species with a range of biologically-relevant modifying agents including radicals, two-electron species and also many electrophiles. Reaction with Cys gives a wide range of both reversible and irreversible species. Lesser numbers of products are well-characterized for cystine and Met. For the latter, the sulfoxide is often the most abundant product, but other species including the cyclic species dehydromethionine, and methionine sulfone have been characterized and shown to be major species under some circumstances. Whilst the sulfone has been widely reported to arise from the sulfoxide as a result of further oxidation, increasing evidence suggests that it can also be formed directly, without the intermediacy of the sulfoxide, and particularly with singlet oxygen ( 1 O 2 ). Whilst the sulfoxide is subject to reduction (e.g. via methionine sulfoxide reductases) and further metabolism in vivo, the sulfone appears to be a stable product and may therefore under certain circumstances be a biomarker of Met oxidation. This article briefly reviews the oxidation chemistry of Cys and cystine, and a more detailed discussion of the mechanisms of Met oxidation, formation of the sulfoxide, dehydromethionine and sulfone, and the biological fates and activities of these species.

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Crossref · 10.1016/j.rbc.2025.100052

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Authors
Davies, M. J.
Affiliations
University of Copenhagen (DK)
Corresponding author
Davies, Michael J.
Venue
Redox Biochemistry and Chemistry
Publisher
Elsevier BV
Published
2025-06
Volume
12
Pages
100052
ISSN
2773-1766 (ISSN-L)
OpenAlex
W4410102286
Cited by
11
References
139
Citations by year
2026: 4 · 2025: 7
FWCI
2.77
Type
journal article
Language
en
Open access
Locations
  • Redox Biochemistry and Chemistry (publishedVersion, cc-by)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Tianjin University
  • Novo Nordisk Foundation (NNF20SA0064214)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
Keywords
methionine oxidation, protein oxidation, oxidative damage biomarkers, methionine sulfoxide, methionine sulfone, cysteine oxidation, cystine oxidation, reactive oxygen species, singlet oxygen, methionine sulfoxide reductase, cellular metabolism, toxicity

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