Differential roles of human monoamine (M)-form and simple phenol (P)-form phenol sulfotransferases in drug metabolism |
| |
Authors: | Sugahara Takuya Pai T Govind Suiko Masahito Sakakibara Yoichi Liu Ming-Cheh |
| |
Institution: | Biomedical Research Center, The University of Texas Health Center, 11937 US HWY 271, Tyler, TX 75708, USA. |
| |
Abstract: | Cytosolic sulfotransferases (STs) are traditionally known as Phase II drug-metabolizing or detoxifying enzymes that facilitate the removal of drugs and other xenobiotic compounds. In this study, we carried out a systematic investigation on the sulfation of drug compounds by two major human phenol STs (PSTs), the monoamine (M)-form and simple phenol (P)-form PSTs. Activity data obtained showed the differential substrate specificity of the two enzymes for the thirteen drug compounds tested. Kinetic studies revealed that the M-form PST displayed stereoselectivity for the chiral drug, isoproterenol. The effects of divalent metal cations on the activity of the M-form and P-form PSTs toward representative drug compounds were quantitatively evaluated. Results obtained indicated that the drug-sulfating activities of the two human PSTs were partially or completely inhibited or stimulated by the ten divalent metal cations tested at a 5 mM concentration. The two enzymes appeared to be less sensitive to the effects of physiologically more abundant metal cations such as Mg(2+) and Ca(2+), but more sensitive to the detrimental effects of other metal cations that may enter the body as environmental contaminants. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|