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Published on: March 28, 2017
Xenobiotic metabolism: a view through the metabolometer
Andrew D Patterson1, Frank J Gonzalez, Jeffrey R Idle
1Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Chemical Research in Toxicology
|March 18, 2010
Summary
Advanced analytical techniques and genetically modified mice significantly expanded our understanding of xenobiotic metabolism, revealing new metabolic pathways and toxicological insights for compounds like PhIP and melatonin.
Area of Science:
- Pharmacology and Toxicology
- Metabolomics
- Biochemistry
Background:
- Xenobiotic metabolism is crucial for understanding drug efficacy and toxicity.
- Current methods often provide incomplete metabolic profiles.
- Genetically modified models offer precise tools for pathway elucidation.
Purpose of the Study:
- To reexamine the metabolism of various xenobiotics using advanced technologies.
- To identify novel metabolic pathways and their enzymatic basis.
- To enhance the understanding of xenobiotic toxicology.
Main Methods:
- Ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS).
- Chemometrics for data analysis.
- Genetically modified mice for enzyme attribution.
Main Results:
- Metabolic maps for PhIP, areca alkaloids, melatonin, and aminoflavone were significantly expanded.
- Novel metabolic pathways were identified and attributed to specific enzymes.
- New insights into the toxicology of these xenobiotics were gained.
Conclusions:
- The integrated approach of UPLC-MS, chemometrics, and transgenic mice is powerful for xenobiotic metabolomics.
- This methodology provides a unique visualization of metabolic space, enhancing toxicological knowledge.
- The approach is adaptable for studying xenobiotic metabolism across species, including humans.
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