title: Uridine Diphosphate-Glucuronosyltransferase (UGT) Xenobiotic Metabolizing Activity and Genetic Evolution in Pinniped Species.
abstract: There are various interspecies differences in xenobiotic-metabolizing enzymes. It is known that cats show slow glucuronidation of drugs such as acetaminophen and strong side effects due to the UGT1A6 pseudogene. Recently, the UGT1A6 pseudogene was found in the Northern elephant seal and Otariidae was suggested to be UGT1A6-deficient. From the results of measurements of uridine diphosphate-glucuronosyltransferase (UGT) activity using liver microsomes, the Steller sea lion, Northern fur seal, and Caspian seal showed UGT activity toward 1-hydroxypyrene and acetaminophen as low as in cats, which was significantly lower than in rat and dog. Furthermore, UGT1A6 pseudogenes were found in Steller sea lion and Northern fur seal, and all Otariidae species were suggested to have the UGT1A6 pseudogene. The UGT1 family genes appear to have undergone birth-and-death evolution based on a phylogenetic and synteny analysis of the UGT1 family in mammals including Carnivora. UGT1A2-1A5 and UGT1A7-1A10 are paralogous genes to UGT1A1 and UGTA6, respectively, and their numbers were lower in cat, ferret and Pacific walrus than in human, rat, and dog. Felidae and Pinnipedia, which are less exposed to natural xenobiotics such as plant-derived toxins due to their carnivorous diet, have experienced fewer gene duplications of xenobiotic-metabolizing UGT genes, and even possess UGT1A6 pseudogenes. Artificial environmental pollutants and drugs conjugated by UGT are increasing dramatically, and their elimination to the environment can be of great consequence to cat and Pinnipedia species, whose low xenobiotic glucuronidation capacity makes them highly sensitive to these compounds.
authors.affiliation: *Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, N18, W9, Kita-ku, Sapporo 060-0818, Japan;
authors.forename: Mayu
authors.initials: M
authors.lastname: Kakehi
authors.affiliation: *Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, N18, W9, Kita-ku, Sapporo 060-0818, Japan; Water Research Group, Unit for Environmental Sciences and Management, North-West University, Potchefstroom, South Africa;
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ikenaka
authors.affiliation: *Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, N18, W9, Kita-ku, Sapporo 060-0818, Japan;
authors.forename: Shouta M M
authors.initials: SM
authors.lastname: Nakayama
authors.affiliation: Diagnostic Center for Animal Health and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan;
authors.forename: Yusuke K
authors.initials: YK
authors.lastname: Kawai
authors.affiliation: *Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, N18, W9, Kita-ku, Sapporo 060-0818, Japan;
authors.forename: Kensuke P
authors.initials: KP
authors.lastname: Watanabe
authors.affiliation: Department of Environmental Veterinary Science, Graduate School of Veterinary Medicine, Hokkaido University, N18, W9, Kita-ku, Sapporo 060-0818, Japan; and.
authors.forename: Hazuki
authors.initials: H
authors.lastname: Mizukawa
authors.affiliation: Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Nomiyama
authors.affiliation: Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Tanabe
authors.affiliation: *Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, N18, W9, Kita-ku, Sapporo 060-0818, Japan; ishizum@vetmed.hokudai.ac.jp.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ishizuka
mesh_terms: D000818:Animals; D010872:Caniformia / Q000235:genetics* / Q000378:metabolism; D002415:Cats; D017124:Conserved Sequence / Q000235:genetics; D004285:Dogs; D019143:Evolution, Molecular; D046069:Fur Seals / Q000235:genetics / Q000378:metabolism; D005796:Genes / Q000235:genetics; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology; D046049:Phoca / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D051381:Rats; D017207:Rats, Sprague-Dawley; D046070:Sea Lions / Q000235:genetics / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D015262:Xenobiotics; D014453:Glucuronosyltransferase
keywords: Carnivores; UGTs; molecular evolution; wildlife; xenobiotic