Rabbani, Naila, Ashour, Amal and Thornalley, Paul J. (2016) Mass spectrometric determination of early and advanced glycation in biology. Glycoconjugates Journal, 33 (4). pp. 533-568. doi:10.1007/s10719-016-9709-8

	PDF WRAP_art%3A10.1007%2Fs10719-016-9709-8.pdf - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1287Kb)
	PDF WRAP_-mv-100616-msdeterminationofglycationinbiologyr1_figs.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer. Download (410Kb)

Request Changes to record.

Abstract

Protein glycation in biological systems occurs predominantly on lysine, arginine and Nterminal residues of proteins. Major quantitative glycation adducts are found at mean extents of modification of 1 – 5 mol percent of proteins. These are glucose-derived fructosamine on
lysine and N-terminal residues of proteins, methylglyoxal-derived hydroimidazolone on arginine residues and Nε-carboxymethyl-lysine residues mainly formed by the oxidative degradation of fructosamine. Total glycation adducts of different types are quantified by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry (LCMS/MS) in multiple reaction monitoring mode. Metabolism of glycated proteins is followed by LC-MS/MS of glycation free adducts as minor components of the amino acid metabolome. Glycated proteins and sites of modification within them – amino acid residues modified by the glycating agent moiety - are identified and quantified by label-free and stable isotope labelling with amino acids in cell culture (SILAC) high resolution mass spectrometry. Sites of glycation by glucose and methylglyoxal in selected proteins are listed. Key issues in applying proteomics techniques to analysis of glycated proteins are: (i) avoiding compromise of analysis by formation, loss and relocation of glycation adducts in pre-analytic processing; (ii) specificity of immunoaffinity enrichment procedures, (iii) maximizing protein sequence coverage in mass spectrometric analysis for detection of glycation sites, and (iv) development of bioinformatics tools for prediction of protein glycation sites. Protein glycation studies have
important applications in biology, ageing and translational medicine – particularly on studies of obesity, diabetes, cardiovascular disease, renal failure, neurological disorders and cancer. Mass spectrometric analysis of glycated proteins has yet to find widespread use clinically.
Future use in health screening, disease diagnosis and therapeutic monitoring, and drug and functional food development is expected. A protocol for high resolution mass spectrometry proteomics of glycated proteins is given.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QH Natural history Q Science > QP Physiology T Technology > TP Chemical technology
Divisions:	Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Mass spectrometry, Proteomics, Glucose, Bioinformatics, Glycosylation
Journal or Publication Title:	Glycoconjugates Journal
Publisher:	Springer New York LLC
ISSN:	0282-0080
Official Date:	August 2016
Dates:	Date Event August 2016 Published 20 July 2016 Available 7 June 2016 Accepted
Date of first compliant deposit:	13 June 2016
Volume:	33
Number:	4
Page Range:	pp. 533-568
DOI:	10.1007/s10719-016-9709-8
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Seventh Framework Programme (European Commission) (FP7), British Heart Foundation, Saudi Arabia. Wizārat al-Taʻlīm al-ʻĀlī

Request changes or add full text files to a record

Repository staff actions (login required)

View Item