Endogenous metabolite profiling

Metabonomics in the context of this chapter aims to define the status and changes of the endogenous metabolite profile in biofluids or tissues of animals or in in vitro systems in response to toxic insults. The most commonly applied... 

LC—MS in Endogenous Metabolite Profiling and Small-Molecule Biomarker Discovery... 

Saghatelian A, Trauger SA, Want EJ, Hawkins EG, Siuzdak G, Cravatt BF, Assignment of Endogenous Substrates to Enzymes by Global Metabolite Profiling, Biochemistry 43 14332—14339, 2004. 

A related approach which in many ways complements drug metabolism analyses is profiling of endogenous metabolites as markers, often done in conjunction with... 

Figure 6.6. Metabolite profiles of omeprazole in human plasma (a) base peak ion chromatogram of unprocessed data and (b) base peak ion chromatogram of MDF-processed data exhibiting all metabolite peaks present and some endogenous peaks. High-resolution LC-MS data were obtained for a human plasma sample spiked with omeprazole metabolites generated by microsomal incubation (the equivalent of a 1.0-mL plasma injection). A MDF ivas set at 50 mDa around the apparent mass defect of the omeprazole ion.

But are there other endogenous substrates for this enzyme A method based on separation techniques and mass spectrometry has been developed to identify endogenous substrates of enzymes by analysis of metabolomes from wild-type and enzyme-inactivated organisms [316], Indeed, the accumulation of metabolites resulting from the inactivation of the enzyme would be considered candidate endogenous substrates for this enzyme. This method based on comparative metabolomics is called discovery metabolites profiling (DMP). 

Saghatelian, A., Trauger, S.A., Want, EJ. et al. (2004) Assignment of endogenous substrates to enzymes by global metabolite profiling. Biochemistry, 43, 14332-9. 

Lenz, E.M., Bright, J., Knight, R., Wilson, I.D., and Major, H. 2004. A metabonomic investigation of the biochemical effects of mercuric chloride in the rat using IH NMR and HPLC-TOF/MS Time dependent changes in the urinary profile of endogenous metabolites as a result of nephrotoxicity. Analyst 129, 535-541. 

These preclinical drug metabolism studies may also include metabolite profiling in plasma, selected tissues, urine, and bile to assess the distribution and disposition of potentially important metabolites, such as those having a level 5% or greater relative to the parent compound. Metabolite profiling requires a technique to separate the parent compound from metabolites and other endogenous compounds. For small organic molecules, HPLC is usually the method of choice. For macromolecules, gel or capillary electrophoresis techniques can be defined with sufficient resolution capability to separate the... 

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