A new glycation product 'norpronyl-lysine, ' and direct characterization of cross linking and other glycation adducts: NMR of model compounds and collagen. Issue 2 (14th March 2014)

• Record Type: Journal Article
• Authors: Bullock, Peter T. B.; Reid, David G.; Ying Chow, W.; Lau, Wendy P. W.; Duer, Melinda J.
• Is Part Of: Bioscience reports. Volume 34:Issue 2(2014)
• Publication Date: 2014-03-14
• Subjects: ADP-ribose -- advanced glycation endproducts -- Maillard reaction -- ribose -- ribose-5-phosphate -- solid-state NMR; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20130135
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract : NMR reveals numerous early and advanced glycation products, including a newly recognized 'norpronyl-lysine, ' and cross links in solution, intact collagen and model systems. Solid state methods are directly applicable to in vitro and in vivo glycation pathway and product characterization. Abstract : NMR is ideal for characterizing non-enzymatic protein glycation, including AGEs (advanced glycation endproducts) underlying tissue pathologies in diabetes and ageing. Ribose, R5P (ribose-5-phosphate) and ADPR (ADP-ribose), could be significant and underinvestigated biological glycating agents especially in chronic inflammation. Using [U- 13 C]ribose we have identified a novel glycoxidation adduct, 5-deoxy-5-desmethylpronyl-lysine, 'norpronyl-lysine', as well as numerous free ketones, acids and amino group reaction products. Glycation by R5P and ADPR proceeds rapidly with R5P generating a brown precipitate with PLL (poly-L -lysine) within hours. ssNMR (solid-state NMR) 13 C– 13 C COSY identifies several crosslinking adducts such as the newly identified norpronyl-lysine, in situ, from the glycating reaction of 13 C5 -ribose with collagen. The same adducts are also identifiable after reaction of collagen with R5P. We also demonstrate for the first time bio-amine (spermidine, N-acetyl lysine, PLL) catalysed ribose 2-epimerization to arabinose at physiological pH. This work raises the prospect of advancing understanding of the mechanisms and consequences of glycation in actual tissues, in vitro or even ex vivo, using NMR isotope-labelled glycating agents, without analyses requiring chemical or enzymatic degradations, or prior assumptions about glycation products.