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Mechanism of Protein Modification by Glyoxal and Glycolaldehyde, Reactive Intermediates of the Maillard Reaction
Open accessAbstract
The role of glyoxal and glycolaldehyde in protein cross-linking and N epsilon-(carboxymethyl)lysine (CML) formation during Maillard reaction under physiological conditions was investigated. Incubation of bovine serum albumin with these reagents lead to rapid formation of C-2-imine cross-links and CML. Initial CML formation rate from glyoxal was not dependent on oxidation, suggesting an intramolecular Cannizzaro reaction. CML formation from glucose/lysine or Amadori product of both was strongly dependent on oxidation. Blocking of Amadori product by boric acid totally suppressed CML formation from Amadori product, but only by 37% in the glucose/lysine system. Trapping of glyoxal with aminoguanidine hardly suppressed CML formation from Amadori product, whereas it blocked 50% of CML production in the glucose/lysine system. While these results would support a significant role for glucose autoxidation in CML formation, the addition of lysine to a glucose/aminoguanidine incubation system catalyzed glyoxal-triazine formation 7-fold, thereby strongly suggesting that glucose autoxidation is not a factor for glyoxal-mediated CML formation. Based on these results, it can be estimated that approximately 50% of the CML forming in a glucose/lysine system originates from oxidation of Amadori product, and 40-50% originates from a pre-Amadori stage largely independent from glucose autoxidation. This step may be related to the so-called Namiki pathway of the Maillard reaction.
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“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 [36]
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Metadata
- Authors
- Glomb, M. A., & Monnier, V. M.
- Affiliations
- Case Western Reserve University (US)
- Corresponding author
- Glomb, Marcus A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-04
- Volume
- 270
- Issue
- 17
- Pages
- 10017-10026
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2017214714
- Cited by
- 576
- References
- 28
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 13 · 2023: 13 · 2022: 12 · 2021: 24 · 2020: 8 · 2019: 12 · 2018: 24 · 2017: 16 · 2016: 19 · 2015: 20 · 2014: 22 · 2013: 19 · 2012: 18
- FWCI
- 11.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag005601-13)
- National Institute on Aging (AG 05601)
- National Eye Institute (EY 07099, R01EY007099)
- 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
- Maillard reaction, glyoxal, glycolaldehyde, carboxymethyllysine, protein cross-linking, bovine serum albumin, Amadori products, Cannizzaro reaction, protein oxidation, boric acid, aminoguanidine
- MeSH terms
- Acetaldehyde, Chromatography, High Pressure Liquid, Chromatography, Thin Layer, Electrophoresis, Polyacrylamide Gel, Glyoxal, Lysine, Gas Chromatography-Mass Spectrometry, Oxidation-Reduction, Proteins, Maillard Reaction
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