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About the Authors:
Binu Shrestha
Affiliations Comparative and Molecular Pharmacogenomics Laboratory, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, Massachusetts, United States of America, Department of Biology, Tufts University, Medford, Massachusetts, United States of America
J. Michael Reed
Affiliation: Department of Biology, Tufts University, Medford, Massachusetts, United States of America
Philip T. Starks
Affiliation: Department of Biology, Tufts University, Medford, Massachusetts, United States of America
Gretchen E. Kaufman
Affiliation: Department of Environmental and Population Health, Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts, United States of America
Jared V. Goldstone
Affiliation: Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts, United States of America
Melody E. Roelke
Affiliation: Laboratory of Genomic Diversity, SAIC-Frederick Incorporated, National Cancer Institute at Frederick, Frederick, Maryland, United States of America
Stephen J. O'Brien
Affiliation: Laboratory of Genomic Diversity, National Cancer Institute at Frederick, Frederick, Maryland, United States of America
Klaus-Peter Koepfli
Affiliation: Laboratory of Genomic Diversity, National Cancer Institute at Frederick, Frederick, Maryland, United States of America
Laurence G. Frank
Affiliation: Living with Lions Project (Kenya), Museum of Vertebrate Zoology, University of California, Berkeley, California, United States of America
Michael H. Court
* E-mail: [email protected]
Affiliation: Comparative and Molecular Pharmacogenomics Laboratory, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, Massachusetts, United States of America
Introduction
Between- and within- species differences in the capacity to metabolize and eliminate drugs and other xenobiotics from the body are typically substantial, complicating the effective use of drugs, as well as minimizing the ability to predict the adverse consequences of environmental pollutants. Slow metabolic clearance leads to enhanced adverse drug effects and the bioaccumulation of pollutants, while fast metabolic clearance minimizes beneficial drug effects. One extreme of the species difference is the so-called ‘species defect’ of drug metabolism - a drug metabolic pathway that is common to most species, but essentially absent in one (or perhaps only a few) species [1]. Perhaps the best known example of a species defect of drug metabolism is the inability of domestic cats to metabolize drugs and structurally related phenolic compounds by glucuronidation [2], [3], [4], [5], [6], [7]. Glucuronidation is catalyzed by the UDP-glucuronosyltransferases (UGTs), a superfamily of conjugative enzymes predominantly found in the liver that transfer glucuronic acid...