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Mass spectrometric determination of early and advanced glycation in biology
Protein glycation in biological systems occurs predominantly on lysine, arginine and N-terminal 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 residue...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975772/ https://www.ncbi.nlm.nih.gov/pubmed/27438287 http://dx.doi.org/10.1007/s10719-016-9709-8 |
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author | Rabbani, Naila Ashour, Amal Thornalley, Paul J |
author_facet | Rabbani, Naila Ashour, Amal Thornalley, Paul J |
author_sort | Rabbani, Naila |
collection | PubMed |
description | Protein glycation in biological systems occurs predominantly on lysine, arginine and N-terminal 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 N(ε)-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 (LC-MS/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. |
format | Online Article Text |
id | pubmed-4975772 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-49757722016-08-18 Mass spectrometric determination of early and advanced glycation in biology Rabbani, Naila Ashour, Amal Thornalley, Paul J Glycoconj J Review Protein glycation in biological systems occurs predominantly on lysine, arginine and N-terminal 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 N(ε)-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 (LC-MS/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. Springer US 2016-07-20 2016 /pmc/articles/PMC4975772/ /pubmed/27438287 http://dx.doi.org/10.1007/s10719-016-9709-8 Text en © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Review Rabbani, Naila Ashour, Amal Thornalley, Paul J Mass spectrometric determination of early and advanced glycation in biology |
title | Mass spectrometric determination of early and advanced glycation in biology |
title_full | Mass spectrometric determination of early and advanced glycation in biology |
title_fullStr | Mass spectrometric determination of early and advanced glycation in biology |
title_full_unstemmed | Mass spectrometric determination of early and advanced glycation in biology |
title_short | Mass spectrometric determination of early and advanced glycation in biology |
title_sort | mass spectrometric determination of early and advanced glycation in biology |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975772/ https://www.ncbi.nlm.nih.gov/pubmed/27438287 http://dx.doi.org/10.1007/s10719-016-9709-8 |
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