J. Biochem, 2003, Vol. 133, No. 2 259-262
© 2003 Japanese Biochemical Society
BIOCHEMISTRY |
Differential Roles of Human Monoamine (M)-Form and Simple Phenol (P)-Form Phenol Sulfotransferases in Drug Metabolism
Biomedical Research Center, The University of Texas Health Center, 11937 US HWY 271, Tyler, TX 75708, USA
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 Mg2+ and Ca2+, but more sensitive to the detrimental effects of other metal cations that may enter the body as environmental contaminants.
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