期刊
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
卷 19, 期 10, 页码 1500-1513出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jasms.2008.06.015
关键词
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资金
- Staff of the Department of Radiation Oncoloy
- Department of Otorhinolaryngology
- Head and Neck Surgery
- University Hospital Tubingen
The physiological response of the human body to several diseases can be reflected by the metabolite pattern in biological fluids. Cancer, like other diseases accompanied by metabolic disorders, causes characteristic effects on cell turnover rate, activity of modifying enzymes, and RNA/DNA modifications. This results in an altered excretion of modified nucleosides and biochemically related compounds. In the course our metabolic profiling project, we screened 24-h Urine of patients suffering from lung, rectal, or head and neck cancer for previously unknown ribosylated metabolites. Therefore, we developed a sample preparation procedure based on boronate affinity chromatography followed by additional prepurification with preparative TLC. The isolated metabolites were analyzed by ion trap mass spectrometry (IT MS) and Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS). IT MS was applied for LC-auto MS3 screening runs and MS( = 4-6) syringe pump infusion experiments, yielding characteristic fragmentation patterns. FTICR MS measurements enabled the calculation of corresponding molecular formulae based on accurate mass determination (mass accuracy: 1-5 ppm for external and sub-ppm values for internal calibration). We were able to identify 22 metabolites deriving from cellular RNA metabolism and related metabolic pathways like histidine metabolism, purine biosynthesis, methionine/polyamine cycle, and nicotinate/nicotinamide metabolism lism. The compounds 1-ribosyl-3-hydroxypyridinium, 1-ribosyl-pyridinium, and 3-ribosyl-1-methyl-L-histidinium as well as a series of ribosylated histamines, conjugated to carboxylic acids at the N-omega -Position were found as novel urinary constituents. The occurrence of the modified nucleosides 2-methylthio-N-6-(cis-hydroxyisopentenyl)-adenosine, 5-methoxycarbonylmethyl-2-thiouridine, N-6-methyl-N-6-threonylcarbamoyladenosine, and 2-methylthio-N-6-threonylcarbamoyladenosine in human urine is verified for the first time. (J Am Soc Mass Spectrom 2008, 19, 1500-1513) (C) 2008 American Society for Mass Spectrometry
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