Sulfation of Environmental Estrogens by Cytosolic Human Sulfotransferases

• NISHIYAMA Takahito

  Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Science

• OGURA Kenichiro

  Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Science

• NAKANO Hiroaki

  Corporate, Scientific and Regulatory Affairs Division, Tobacco Headquarters, Japan Tobacco Inc.

• KAKU Teppei

  Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Science

• TAKAHASHI Eriko

  Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Science

• OHKUBO Yasunari

  Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Science

• SEKINE Koji

  Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Science

• HIRATSUKA Akira

  Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Science

• KADOTA Shigetoshi

  Institute of Natural Medicine, Toyama Medical and Pharmaceutical University

• WATABE Tadashi

  Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Science Institute of Natural Medicine, Toyama Medical and Pharmaceutical University

抄録

  It is known that in humans taking soy food, the phytoestrogens, daidzein (DZ) and genistein (GS), exist as sulfates and glucuronides in the plasma and are excreted as conjugates in urine. To investigate which human sulfotransferase (SULT) isoforms participate in the sulfation of these phytoestrogens, the four major cytosolic SULTs, SULT1A1, SULT1A3, SULT1E1, and SULT2A1, occurring in the human liver were bacterially expressed as His-tagged proteins and chromatographically purified to homogeneity in the presence of Tween 20 and glycerol as highly efficient agents for stabilizing the recombinant enzymes. All the SULTs showed sulfating activity toward both DZ and GS. However, k_cat/K_m values observed indicated that these phytoestrogens were sulfated predominantly by SULT1A1 and SULT1E1 with K_m values of 0.3 and 0.7 μM for GS and 1.9 and 3.4 μM for DZ, respectively. DZ and GS strongly inhibited the sulfation of the endogenous substrate, β-estradiol, by SULT1E1 in a non-competitive manner with K_i values of 14 and 7 μM, respectively, suggesting that these phytoestrogens might affect tissue levels of β-estradiol in the human. The phenolic endocrine-disrupting chemicals, bisphenol A (BPA), 4-n-nonylphenol (NP), and 4-t-octylphenol (t-OP), were used as substrates to investigate the possible participation of human SULTs in their metabolism for excretion. High k_cat/K_m values were observed for the sulfation of BPA by SULT1A1, NP by SULT1A1 and SULT1E1, and t-OP by SULT1E1 and SULT2A1.<br>

収録刊行物

• Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ

  Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 17 (3), 221-228, 2002

  日本薬物動態学会

キーワード

• environmental estrogen
• endocrine-disrupting chemicals
• human
• kinetic parameter
• sulfotransferase
• phytoestrogen

詳細情報

• CRID: 1390282680155945856
• NII論文ID: 10009506347
• NII書誌ID: AA1162652X
• DOI: 10.2133/dmpk.17.221
• COI: 1:CAS:528:DC%2BD38XnsV2ltbs%3D
• ISSN: 18800920
• ISSN: 13474367
• Web Site: http://api.elsevier.com/content/article/PII:S134743671530937X?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S134743671530937X?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2003034852
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可