Hydrolytic drug-metabolising enzymes – tissue distribution and interspecies differences

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Protein Abundance of Hydrolytic Drug Metabolizing Enzymes in Different Tissues and across Species

 Summary

• Global proteomics study compared hydrolytic drug-metabolising enzymes (DMEs) across human, rat, mouse, dog, and monkey tissues
• Mapped 182 enzymes in the liver, intestine, and kidney, with detailed quantification of 12 hydrolytic DMEs
• Found significant tissue- and species-specific differences in the presence and abundance of key hydrolases (e.g., CES1, CES2, AADAC, and PON enzymes)
• Humans showed the greatest diversity of hydrolases shared across tissues
• Marked species differences in  enzyme abundance and orthology, especially for CES isoforms
• Highlights limitations of direct cross-species comparisons.
• Emphasises the importance of selecting appropriate animal models for drug metabolism studies involving hydrolases.

The findings in this paper provide a framework to improve translation of in vitro data and animal studies to humans for such enzymes. In particular the importance of careful selection of animal models for drug metabolism studies. This is particularly relevant in light of the significant contribution of hydrolases in the metabolism of drugs and the diversity of enzymes in this group.

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