The Advanced Glycation End Product, N∊-(Carboxymethyl)lysine, Is a Product of both Lipid Peroxidation and Glycoxidation Reactions
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Nepsilon-(Carboxymethyl)lysine (CML) is an advanced glycation end product formed on protein by combined nonenzymatic glycation and oxidation (glycoxidation) reactions. We now report that CML is also formed during metal-catalyzed oxidation of polyunsaturated fatty acids in the presence of protein. During copper-catalyzed oxidation in vitro, the CML content of low density lipoprotein increased in concert with conjugated dienes but was independent of the presence of the Amadori compound, fructoselysine, on the protein. CML was also formed in a time-dependent manner in RNase incubated under aerobic conditions in phosphate buffer containing arachidonate or linoleate; only trace amounts of CML were formed from oleate. After 6 days of incubation the yield of CML in RNase from arachidonate was approximately 0.7 mmol/mol lysine compared with only 0.03 mmol/mol lysine for protein incubated under the same conditions with glucose. Glyoxal, a known precursor of CML, was also formed during incubation of RNase with arachidonate. These results suggest that lipid peroxidation, as well as glycoxidation, may be an important source of CML in tissue proteins in vivo and that CML may be a general marker of oxidative stress and long term damage to protein in aging, atherosclerosis, and diabetes.
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CML is considered not only an AGE but also an advanced lipoxidation endproduct (ALE).
“Hence, CML is not only considered as an AGE, but also as an advanced lipoxidation endproduct (ALE) [48].”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [48]
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- Authors
- Fu, M.-X., Requena, J. R., Jenkins, A. J., Lyons, T. J., Baynes, J. W., & Thorpe, S. R.
- Affiliations
- University of South Carolina (US)
- Medical University of South Carolina (US)
- Corresponding author
- Thorpe, Suzanne R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1996-04
- Volume
- 271
- Issue
- 17
- Pages
- 9982-9986
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2108448809
- Cited by
- 822
- References
- 1
- Citations by year
- 2026: 14 · 2025: 18 · 2024: 18 · 2023: 19 · 2022: 25 · 2021: 34 · 2020: 25 · 2019: 21 · 2018: 26 · 2017: 35 · 2016: 33 · 2015: 32 · 2014: 29 · 2013: 32 · 2012: 31
- FWCI
- 19.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- National Institute on Aging (AG-11471)
- National Eye Institute (R29EY010697)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Agricultural and Biological Sciences › Food Science › Potato Plant Research
- Keywords
- carboxymethyllysine, advanced glycation end products, lipid peroxidation, glycoxidation, copper-catalyzed oxidation, polyunsaturated fatty acids, arachidonic acid, linoleic acid, low-density lipoprotein, ribonuclease, glyoxal, oxidative stress, protein oxidation, aging, atherosclerosis, diabetes mellitus
- MeSH terms
- Copper, Glyoxal, Humans, Lipid Peroxides, Lipoproteins, LDL, Lysine, Oxidation-Reduction, Arachidonic Acid, Glycation End Products, Advanced
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