Sulfotransferases (SULTs), enzymatic and genetic variation in Carnivora : Limited sulfation capacity in pinnipeds

Kondo, Mitsuki; Ikenaka, Yoshinori; Nakayama, Shouta M. M.; Kawai, Yusuke K.; Mizukawa, Hazuki; Mitani, Yoko; Nomyama, Kei; Tanabe, Shinsuke; Ishizuka, Mayumi

Sulfotransferases (SULTs), enzymatic and genetic variation in Carnivora : Limited sulfation capacity in pinnipeds

Kondo, Mitsuki; Ikenaka, Yoshinori; Nakayama, Shouta M. M. et al.

Comparative biochemistry and physiology Part C: Toxicology & pharmacology, 2023, 263, 109476

Permalink : https://hdl.handle.net/2115/91043

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アクセス権	open access
URI	https://hdl.handle.net/2115/91043
タイトル	Sulfotransferases (SULTs), enzymatic and genetic variation in Carnivora : Limited sulfation capacity in pinnipeds
著者	Kondo, Mitsuki ; Ikenaka, Yoshinori ; Nakayama, Shouta M. M. ; Kawai, Yusuke K. ; Mizukawa, Hazuki ; Mitani, Yoko ; Nomyama, Kei ; Tanabe, Shinsuke ; Ishizuka, Mayumi
著者名 Kondo, Mitsuki
著者名 Ikenaka, Yoshinori
著者名 Nakayama, Shouta M. M.
著者名 Kawai, Yusuke K.
著者名 Mizukawa, Hazuki
著者名 Mitani, Yoko
著者名 Nomyama, Kei
著者名 Tanabe, Shinsuke
e-Rad_Researcher 50332474 著者名 Ishizuka, Mayumi
言語	英語
キーワード	Wildlife
	Xenobiotic metabolism
	In silico analysis
	Genome database
	Phase II metabolism
発行日	2023-01
出版者	Elsevier
収録物名	Comparative biochemistry and physiology Part C: Toxicology & pharmacology
巻(号)	263
ページ	109476
抄録	Wild carnivorans are one of the most important species due to their high positions in the food chain. They are also highly affected by numerous environmental contaminants through bioaccumulation and biomagnification. Xenobiotic metabolism is a significant chemical defense system from xenobiotics because it degrades the activity of a wide range of chemicals, generally into less active forms, resulting in their deactivation. Sulfotransferases (SULTs) are one of the most important xenobiotic metabolic enzymes, which catalyze the sulfonation of a variety of endogenous and exogenous chemicals, such as hormones, neurotransmitters, and a wide range of xenobiotic compounds. Although SULTs are of such high importance, little research has focused on these enzymes in wild carnivorans. In this study, we clarified the genetic properties of SULTs in a wide range of mammals, focusing on carnivorans, using in silico genetic analyses. We found genetic deficiencies of SULT1E1 and SULT1D1 isoforms in all pinnipeds analyzed and nonsense mutations in SULT1Cs in several carnivorans including pinnipeds. We further investigated the enzymatic activity of SULT1E1 in vitro using liver cytosols from pinnipeds. Using a SULT1E1 probe substrate, we found highly limited estradiol sulfonation in pinnipeds, whereas other mammals had relatively high sulfation. These results suggest that pinnipeds have severely or completely absent SULT1E1 activity, which importantly catalyzes the metabolism of estrogens, drugs, and environmental toxins. This further implies a high susceptibility to a wide range of xenobiotics in these carnivorans, which are constantly exposed to environmental chemicals throughout their lifetime.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2023. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	1532-0456
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.cbpc.2022.109476