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Glycation is a non-enzymatic modification formed by reaction of reducing sugars with amino groups of proteins. Resulting Amadori compounds oxidize ('glycoxidation'), yielding advanced glycation end-products (AGEs), a heterogeneous group of potentially pro-inflammatory compounds. Alternatively, carbohydrates are involved in formation of α-dicarbonyls, yielding AGEs upon reaction with lysyl and arginyl residues ('oxidative glycosylation'). Despite the well-known deteriorating effect of AGEs, the exact formation mechanisms, relative contribution and possible interference of these pathways are unknown. Therefore, here we address glycation potential of dietary sugars and estimate the contribution of the major glycation pathways in formation of corresponding AGEs. Our experiments relied on model glycation systems, based on synthetic peptides, their Amadori modified counterparts and selected dietary sugar (or, in some cases, their 13C-labeled analogs). Thereby, all AGE-formation pathways can be considered simultaneously. Analysis of peptide, sugar and α-dicarbonyl intermediates will rely on RP-UHPLC-ESI-QqTOF-, GC-Q-EI- and RP-HPLC-IT-MS, in two latter cases, after appropriate derivatization. The structures of peptide products and sugar intermediates were identified by their MS/MS fragmentation patterns, whereas annotation of carbonyl compounds relied on EI patterns and co-elution with authentic standards. Individual glycation pathways were assigned by isotopic composition of products. Analysis of the glycation mixtures revealed 37 lysine- and 22 argininederived products. Annotation of the glycation pathways, assigned to the generation of lysine-derived AGEs, revealed their formation via several routes: (i) both glycoxidative and autoxidative pathways (α-amino semiadipic aldehyde-containing product and peptide fragments), (ii) mostly via “glycoxidation”, i.e. Amadori degradation (carboxymethylated peptides) or (iii) “autoxidative glycosylation” (pyrraline). This data were supported by kinetics profile of approximately 30 carbonyl compounds. To summarize, our approach allowed identification of the major routes for formation of specific AGEs. This project was supported by Deutsche Forschungsgemeinschaft (grant number FR3117/2-3) and RFBR (research project number 18-34-00927).
Original languageEnglish
Title of host publicationII Объединенный научный форум: VI Съезд биохимиков России и IX Российский симпозиум «Белки и пептиды»
Subtitle of host publicationНаучные труды
Place of PublicationМ.
PublisherИздательство «Перо»
Pages276
Volume2
ISBN (Print)9785001505198 , 9785001505211 (Т. 2)
StatePublished - 2019
EventII Объединенный научный форум: VI Съезд биохимиков России и IX Российский симпозиум «Белки и пептиды»: Научные труды - Сочи-Дагомыс, Russian Federation
Duration: 1 Oct 20196 Oct 2019
Conference number: 6
http://www.rusbiochem.org/page206.html

Publication series

NameACTA NATURAE (РУССКОЯЗЫЧНАЯ ВЕРСИЯ)
PublisherПарк-медиа
ISSN (Print)2075-8243

Conference

ConferenceII Объединенный научный форум: VI Съезд биохимиков России и IX Российский симпозиум «Белки и пептиды»: Научные труды
Country/TerritoryRussian Federation
CityСочи-Дагомыс
Period1/10/196/10/19
Internet address

    Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)

ID: 49589808