Extending the spectrum of α-dicarbonyl compounds in vivo
| Autor: | Christian Henning, Christof Ulrich, Matthias Girndt, Marcus A. Glomb, Kristin Liehr |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Glycation End Products Advanced Male education Carboxylic Acids Phenylenediamines Biochemistry chemistry.chemical_compound symbols.namesake Glycation Limit of Detection Renal Dialysis Tandem Mass Spectrometry Ketoses Humans Metabolomics Molecular Biology Glyoxylic acid Aged Uremia chemistry.chemical_classification Aged 80 and over Aldehydes Chromatography Methylglyoxal Reproducibility of Results Molecular Bases of Disease Cell Biology Hydrogen-Ion Concentration Middle Aged Ascorbic acid Maillard Reaction Maillard reaction Dicarboxylic acid chemistry Case-Control Studies symbols Dehydroascorbic acid Female Pyruvic acid Chromatography Liquid |
| Zdroj: | The Journal of biological chemistry. 289(41) |
| ISSN: | 1083-351X |
| Popis: | Maillard α-dicarbonyl compounds are known as central intermediates in advanced glycation end product (AGE) formation. Glucose is the primary source of energy for the human body, whereas l-threo-ascorbic acid (vitamin C) is an essential nutrient, involved in a variety of enzymatic reactions. Thus, the Maillard degradation of glucose and ascorbic acid is of major importance in vivo. To understand the complex mechanistic pathways of AGE formation, it is crucial to extend the knowledge on plasma concentrations of reactive key α-dicarbonyl compounds (e.g. 1-deoxyglucosone). With the present work, we introduce a highly sensitive LC-MS/MS multimethod for human blood plasma based on derivatization with o-phenylenediamine under acidic conditions. The impact of workup and reaction conditions, particularly of pH, was thoroughly evaluated. A comprehensive validation provided the limit of detection, limit of quantitation, coefficients of variation, and recovery rates. The method includes the α-dicarbonyls 1-deoxyglucosone, 3-deoxyglucosone, glucosone, Lederer's glucosone, dehydroascorbic acid, 2,3-diketogulonic acid, 1-deoxypentosone, 3-deoxypentosone, 3,4-dideoxypentosone, pentosone, 1-deoxythreosone, 3-deoxythreosone, threosone, methylglyoxal, glyoxal; the α-keto-carboxylic acids pyruvic acid and glyoxylic acid; and the dicarboxylic acid oxalic acid. The method was then applied to the analyses of 15 healthy subjects and 24 uremic patients undergoing hemodialysis. The comparison of the results revealed a clear shift in the product spectrum. In most cases, the plasma levels of target analytes were significantly higher. Thus, this is the first time that a complete spectrum of α-dicarbonyl compounds relevant in vivo has been established. The results provide further insights into the chemistry of AGE formation and will be helpful to find specific markers to differentiate between the various precursors of glycation. |
| Databáze: | OpenAIRE |
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