A new glycation product 'norpronyl-lysine,' and direct characterization of cross linking and other glycation adducts: NMR of model compounds and collagen.

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-13C]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) 13C-13C COSY identifies several crosslinking adducts such as the newly identified norpronyl-lysine, in situ, from the glycating reaction of 13C5-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.

journal_name

Biosci Rep

journal_title

Bioscience reports

authors

Bullock PT,Reid DG,Ying Chow W,Lau WP,Duer MJ

doi

10.1042/BSR20130135

subject

Has Abstract

pub_date

2014-04-01 00:00:00

issue

2

eissn

0144-8463

issn

1573-4935

pii

BSR20130135

journal_volume

34

pub_type

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