Previous Topic Back Forward Next Topic
Print Page Frank Dieterle
Research TutorialsResearch Tutorials MetabonomicsMetabonomics Applications in Drug DevelopmentApplications in Drug Development Structure Elucidation of New BiomarkersStructure Elucidation of New Biomarkers Competitive StudyCompetitive Study Biochemical InterpretationBiochemical Interpretation
About Me
Ph. D. Thesis
Research Tutorials
    Biology and "-omics"
    Definition of Metabonomics
    Applications in Drug Development
      Possiblities and Examples
      Specific Biomarkers
      Patterns of Biomarkers
      Structure Elucidation of New Biomarkers
        Competitive Study
          Metabolite Enrichement
          HNBC 2D-NMR
          Biochemical Interpretation
        Ranking Study
Downloads and Links
Site Map
Print this Page Print this Page

Structure Elucidation - Embedding the New Metabolite into a Biochemical Environment

The new metabolite, which is a N-substituted-S-isoprenol-L-cysteinyl derivative, can be embedded into the biochemical environment of significantly change metabolites. The best way of looking at biochemical environements is looking at pathways (if available). The figure shows a simplified version of biochemical pathways. The metabolites marked by yellow circles were significantly up-regulated for dosed animals. It is obvious that these metabolites are all connected to serine and cysteine marked by magenta circles. Interestingly, the new metabolite is synthesized from cysteine and isopentenylphosphate. It is assumed that isopentenyl-phosphate is a scavenger for increased concentrations of cysteine. Thereby, isopentenylphosphate is no longer available for the steroid and cholesterol synthesis. Therefore the steroid synthesis is affected, which was independently assumed by toxicologists and which is known meanwhile. This example demonstrates the power of metabonomics starting with an unbiased profiling of all known and unknown metabolites and ending with a structure elucidation of new unknown metabolites and a biochemical interpretation of the findings.

Biochemical environment in terms of pathways for the new metabolite. Metabolites marked by yellow circles are significantly increased in urine and are all connected to serine and cysteine. The new metabolite is synthesized from cysteine and isopentenyl-phosphate, which is no longer available for the biosynthesis of steroids and cholesterol.




Page 189 © Frank Dieterle, 03.03.2019 Navigation