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Rapid Formation of Advanced Glycation End Products by Intermediate Metabolites of Glycolytic Pathway and Polyol Pathway
Abstract
To clarify roles of intermediate metabolites of the glycolytic pathway and the polyol pathway in nonenzymatic glycation under physiological conditions, we incubated bovine serum albumin with intermediates of both pathways in the micromolar range as well as with 20 mmol/l glucose, and observed the formation of advanced glycation end products (AGEs). We found that triose phosphates, glyceraldehyde, and a novel polyol pathway-related metabolite, fructose 3-phosphate along with its breakdown product, 3-deoxyglucosone were extremely potent glycating agents that at nearly physiological concentrations on incubation with albumin produced substantial amounts of AGEs as early as 24 hours, while 20 mmol/l glucose afforded trace amounts of AGEs after two week incubation. The results along with the previous evidence of the increased level of intermediates in diabetic states may suggest that the intermediate metabolites rather than glucose contribute to enhanced glycation in diabetic tissues, inspite of the much lower concentrations compared with glucose.
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“Excess glucose is metabolized through the polyol pathway to fructose and its metabolites, which are potent glycating agents.”
From The Vasculature in Prediabetes (2018) · cites this paper as [54]
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Mechanisms of Diabetic Complications
Forbes, J. M., & Cooper, M. E. (2013) · Physiological Reviews · doi:10.1152/physrev.00045.2011 · Cited by 2,890
“glycolytic or Kreb’s cycle intermediates or reactive oxygen species would also lead to modification of proteins by advanced glycation (230).”
BackgroundMolecular Understanding of Hyperglycemia's Adverse Effects for Diabetic Complications
Sheetz, M. J. (2002) · JAMA · doi:10.1001/jama.288.20.2579 · Cited by 1,005
Advanced Glycation End Products and Diabetes Mellitus: Mechanisms and Perspectives
Khalid, M., Petroianu, G. A., & Adem, A. (2022) · Biomolecules · doi:10.3390/biom12040542 · Cited by 972
Kislinger, T., Fu, C., Huber, B., Qu, W., Taguchi, A., Yan, S. D., Hofmann, M. A., Yan, S. F., Pischetsrieder, M., Stern, D. M., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.44.31740 · Cited by 868
Vistoli, G., De Maddis, D., Cipak, A., Zarkovic, N., Carini, M., & Aldini, G. (2013) · Free Radical Research · doi:10.3109/10715762.2013.815348 · Cited by 823
Metadata
- Authors
- Hamada, Y., Araki, N., Koh, N., Nakamura, J., Horiuchi, S., & Hotta, N.
- Affiliations
- Nagoya University (JP)
- Kumamoto University (JP)
- Nagoya University Hospital (JP)
- Corresponding author
- Hamada, Yoji
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 1996-11
- Volume
- 228
- Issue
- 2
- Pages
- 539-543
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2035592628
- Cited by
- 169
- References
- 0
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 5 · 2023: 8 · 2022: 5 · 2021: 8 · 2020: 1 · 2019: 6 · 2018: 8 · 2017: 6 · 2016: 5 · 2015: 10 · 2014: 7 · 2013: 6 · 2012: 5
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- 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
- advanced glycation end products, glycation, polyol pathway, 3-deoxyglucosone, glyceraldehyde, triose phosphate, bovine serum albumin, diabetes mellitus
- MeSH terms
- Glycated Serum Albumin, Animals, Cattle, Deoxyglucose, Glucose, Glyceraldehyde, Glycolysis, Glycosylation, Kinetics, Serum Albumin, Serum Albumin, Bovine, Sorbitol, Substrate Specificity, Sugar Phosphates, Glycation End Products, Advanced
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