Differential xenoestrogen-sulfating activities of the human cytosolic sulfotransferases: molecular cloning, expression, and purification of human SULT2B1a and SULT2B1b sulfotransferases.
Environmental xenoestrogens have been implicated in human reproductive disorders and an increased incidence of breast cancer. Sulfation, a Phase II detoxification mechanism involving the cytosolic sulfotransferases (STs), may be an important mechanism in vivo for fending off these compounds. In this study, we report on the molecular cloning, expression, and purification of two human cytosolic STs, SULT2B1a and SULT2b1b. The activities of these two enzymes, as well as the other eight known human cytosolic STs previously prepared, toward representative environmental xenoestrogens were examined. Activity data showed that P-form (SULT1A1) PST displayed the highest activity toward these compounds, while SULT1C ST #2 also showed considerable activity, indicating that these enzymes may play a more important role in detoxification of environmental xenoestrogens. SULT1C ST #1, SULT2B1a ST, SULT2B1b ST and NST showed negligible or undetectable activity toward these compounds. The other four enzymes, M-form (SULT1A3) PST, SULT1B2 ST, SULT2A1 ST and SULT1E ST showed intermediate levels of activity toward some of these compounds. Kinetic studies on the sulfation of xenoestrogens by P-form (SULT1A1) PST were performed. The results are interpreted in the context of the endocrine-disrupting nature of these xenoestrogens.
Pai
T Govind
TG
Department of Biochemistry, Biomedical Research Center, The University of Texas Health Center at Tyler, 11937 US HWY 271, Tyler, TX 75708, USA.
Sugahara
Takuya
T
Suiko
Masahito
M
Sakakibara
Yoichi
Y
Xu
Faye
F
Liu
Ming-Cheh
MC
D000393:Air Pollutants / Q000737:chemistry; D003001:Cloning, Molecular; D003600:Cytosol / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015262:Xenobiotics / Q000737:chemistry
D000393:Air Pollutants; D007527:Isoenzymes; D015262:Xenobiotics; D015238:Sulfotransferases; C433248:SULT2B1 protein, human