Identification of N epsilon-carboxymethyllysine as a degradation product of fructoselysine in glycated protein.
Open accessAbstract
The chemistry of Maillard or browning reactions of glycated proteins was studied using the model compound, N alpha-formyl-N epsilon-fructoselysine (fFL), an analog of glycated lysine residues in protein. Incubation of fFL (15 mM) at physiological pH and temperature in 0.2 M phosphate buffer resulted in formation of N epsilon-carboxymethyllysine (CML) in about 40% yield after 15 days. CML was formed by oxidative cleavage of fFL between C-2 and C-3 of the carbohydrate chain and erythronic acid (EA) was identified as the split product formed in the reaction. Neither CML nor EA was formed from fFL under a nitrogen atmosphere. The rate of formation of CML was dependent on phosphate concentration in the incubation mixture and the reaction was shown to occur by a free radical mechanism. CML was also identified by amino acid analysis in hydrolysates of both poly-L-lysine and bovine pancreatic ribonuclease glycated in phosphate buffer under air. CML was also detected in human lens proteins and tissue collagens by HPLC and the identification was confirmed by gas chromatography/mass spectroscopy. The presence of both CML and EA in human urine suggests that they are formed by degradation of glycated proteins in vivo. The browning of fFL incubation mixtures proceeded to a greater extent under a nitrogen versus an air atmosphere, suggesting that oxidative degradation of Amadori adducts to form CML may limit the browning reactions of glycated proteins. Since the reaction products, CML and EA, are relatively inert, both chemically and metabolically, oxidative cleavage of Amadori adducts may have a role in limiting the consequences of protein glycation in the body.
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CML is formed by oxidative degradation of fructoselysine (Amadori product) and alternatively by reaction of the α-dicarbonyl compound glyoxal with lysine via an isomerization mechanism.
“CML was the first discovered glycoxidation product and is formed by oxidative degradation of fructoselysine (Amadori product) [35]. An alternative pathway is the reaction between the α-dicarbonyl compound glyoxal and lysine leading to CML formation via an isomerization mechanism [36].”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [35]
Carboxymethyllysine is one of many advanced glycation end products generated by oxidation of carbohydrate.
“carboxymethyllysine is one of many advanced glycation end products (AGEs) generated by oxidation of carbohydrate (24).”
From Drusen proteome analysis: an approach to the etiology of age-related macular degeneration (2002) · cites this paper as [24]
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- Authors
- Ahmed, M. U., Thorpe, S. R., & Baynes, J. W.
- Affiliations
- University of South Carolina (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1986-04
- Volume
- 261
- Issue
- 11
- Pages
- 4889-4894
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1609735481
- Cited by
- 864
- References
- 24
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 17 · 2023: 13 · 2022: 22 · 2021: 22 · 2020: 22 · 2019: 25 · 2018: 18 · 2017: 27 · 2016: 30 · 2015: 20 · 2014: 24 · 2013: 27 · 2012: 20
- FWCI
- 6.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Scholar Commons (University of South Carolina) (submittedVersion)
- Funders
- National Institutes of Health (5k04am000931-04, 5r01am019971-09)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Agricultural and Biological Sciences › Food Science › Potato Plant Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Keywords
- carboxymethyllysine, fructoselysine, glycated proteins, Maillard reaction, browning reaction, oxidative cleavage, radical mechanism, protein glycation, poly-L-lysine, bovine pancreatic ribonuclease, human lens proteins, collagen, human urine, phosphate concentration
- MeSH terms
- Chemistry, Chromatography, High Pressure Liquid, Crystallins, Free Radicals, Glycoproteins, Humans, Hydrogen-Ion Concentration, Kinetics, Lysine, Gas Chromatography-Mass Spectrometry, Middle Aged, Mucoproteins, Oxidation-Reduction, Phosphates, Chemical Phenomena
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