Differential roles of human monoamine (M)-form and simple phenol (P)-form phenol sulfotransferases in drug metabolism.
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.
Sugahara
Takuya
T
Biomedical Research Center, The University of Texas Health Center, 11937 US HWY 271, Tyler, TX 75708, USA.
Pai
T Govind
TG
Suiko
Masahito
M
Sakakibara
Yoichi
Y
Liu
Ming-Cheh
MC
D015239:Arylsulfotransferase / Q000378:metabolism* / Q000502:physiology; D002413:Cations, Divalent / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D007545:Isoproterenol / Q000378:metabolism; D007700:Kinetics; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity; D013431:Sulfates
D002413:Cations, Divalent; D004364:Pharmaceutical Preparations; D013431:Sulfates; D015239:Arylsulfotransferase; D007545:Isoproterenol