Sulfation of ritodrine by the human cytosolic sulfotransferases (SULTs): Effects of SULT1A3 genetic polymorphism.
Previous studies have demonstrated the metabolism of ritodrine through sulfation. The current study was designed to identify the human SULTs that are capable of sulfating ritodrine and to investigate how genetic polymorphism of the major ritodrine-sulfating SULT, SULT1A3, may affect its sulfating activity. A systematic analysis revealed that of the 13 known human SULTs, SULT1A1, SULT1A3, and SULT1C4, were capable of mediating the sulfation of ritodrine, with SULT1A3 displaying the strongest sulfating activity. Effects of genetic polymorphism on the sulfating activity of SULT1A3 were examined. By employing site-directed mutagenesis, 4 SULT1A3 allozymes were generated, expressed, and purified. Purified SULT1A3 allozymes were shown to exhibit differential sulfating activity toward ritodrine. Kinetic studies further demonstrated differential substrate affinity and catalytic efficiency among the SULT1A3 allozymes. Collectively, these results provided useful information concerning the differential metabolism of ritodrine through sulfation in different individuals.
Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA; Department of Obstetrics and Gynecology, Beijing Hospital, Beijing 100730, China.
Ying
Y
Hui
Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA. Electronic address: ming.liu@utoledo.edu.
Ming-Cheh
MC
Liu
D015239:Arylsulfotransferase / Q000235:genetics* / Q000378:metabolism*; D001711:Biotransformation; D002384:Catalysis; D005838:Genotype; D006801:Humans; D007527:Isoenzymes; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012312:Ritodrine / Q000378:metabolism*; D013379:Substrate Specificity; D013431:Sulfates / Q000378:metabolism*
D007527:Isoenzymes; D011994:Recombinant Proteins; D013431:Sulfates; D015239:Arylsulfotransferase; C403170:monoamine-sulfating phenol sulfotransferase; D012312:Ritodrine
Cytosolic sulfotransferase; Genetic polymorphism; Ritodrine; SULT; SULT1A3; Sulfation