Development and validation of GC–MS methods for the comprehensive analysis of amino acids in plasma and urine and applications to the HELLP syndrome and pediatric kidney transplantation: evidence of altered methylation, transamidination, and arginase activity
| Autor: | Stephan Ruben, Stefan Ückert, Dimitrios Tsikas, Constantin von Kaisenberg, Alexander Bollenbach, Anibh M. Das, Dieter Haffner, Martin Kreuzer, Frauke von Versen-Höynck, Erik Hanff, Arslan Arinc Kayacelebi |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
0301 basic medicine HELLP Syndrome Adolescent Arginine Clinical Biochemistry Amidines Pilot Projects Urine Pharmacology Mycophenolate Methylation Biochemistry Gas Chromatography-Mass Spectrometry 03 medical and health sciences chemistry.chemical_compound Pregnancy Humans Amino Acids Active metabolite Arginase 030102 biochemistry & molecular biology Organic Chemistry Kidney Transplantation Blood proteins Guanidinoacetate N-methyltransferase Cross-Sectional Studies 030104 developmental biology chemistry Case-Control Studies Female Kidney Diseases Asymmetric dimethylarginine Immunosuppressive Agents |
| Zdroj: | Amino Acids. 51:529-547 |
| ISSN: | 1438-2199 0939-4451 |
| DOI: | 10.1007/s00726-018-02688-w |
| Popis: | We developed and validated gas chromatography-mass spectrometry (GC-MS) methods for the simultaneous measurement of amino acids and their metabolites in 10-µL aliquots of human plasma and urine. De novo synthesized trideutero-methyl esters were used as internal standards. Plasma proteins were precipitated by acidified methanol and removed by centrifugation. Supernatants and native urine were evaporated to dryness. Amino acids were first esterified using 2 M HCl in methanol and then amidated using pentafluoropropionic anhydride for electron-capture negative-ion chemical ionization. Time programmes were used for the gas chromatograph oven and the selected-ion monitoring of specific anions. The GC-MS methods were applied in clinical studies on the HELLP syndrome and pediatric kidney transplantation (KTx) focusing on L-arginine-related pathways. We found lower sarcosine (N-methylglycine) and higher asymmetric dimethylarginine (ADMA) plasma concentrations in HELLP syndrome women (n = 7) compared to healthy pregnant women (n = 5) indicating altered methylation. In plasma of pediatric KTx patients, lower guanidinoacetate and homoarginine concentrations were found in plasma but not in urine samples of patients treated with standard mycophenolate mofetil-based immunosuppression (MMF; n = 22) in comparison to matched patients treated with MMF-free immunosuppression (n = 22). On average, the global arginine bioavailability ratio was by about 40% lower in the MMF group compared to the EVR group (P = 0.004). Mycophenolate, the major pharmacologically active metabolite of MMF, is likely to inhibit the arginine:glycine amidinotransferase (AGAT), and to enhance arginase activity in leukocytes and other types of cell of MMF-treated children. |
| Databáze: | OpenAIRE |
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