Effects of the human SULT1A1 polymorphisms on the sulfation of acetaminophen,O-desmethylnaproxen,and tapentadol |
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Authors: | Mohammed I. Rasool Ahsan F. Bairam Saud A. Gohal Amal A. El Daibani Fatemah A. Alherz Maryam S. Abunnaja Eid S. Alatwi Katsuhisa Kurogi Ming-Cheh Liu |
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Affiliation: | 1. Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614, USA;2. Department of Pharmacology, College of Pharmacy, University of Karbala, Karbala, Iraq;3. Department of Pharmacology, College of Pharmacy, University of Kufa, Najaf, Iraq;4. Biochemistry and Applied Biosciences, University of Miyazaki, Miyazaki 889-2192, Japan |
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Abstract: | BackgroundNon-opioid and opioid analgesics, as over-the-counter or prescribed medications, are widely used for the management of a diverse array of pathophysiological conditions. Previous studies have demonstrated the involvement of human cytosolic sulfotransferase (SULT) SULT1A1 in the sulfation of acetaminophen, O-desmethylnaproxen (O-DMN), and tapentadol. The current study was designed to investigate the impact of single nucleotide polymorphisms (SNPs) of the human SULT1A1 gene on the sulfation of these analgesic compounds by SULT1A1 allozymes.MethodsHuman SULT1A1 genotypes were identified by database search. cDNAs corresponding to nine SULT1A1 nonsynonymous missense coding SNPs (cSNPs) were generated by site-directed mutagenesis. Recombinant wild-type and SULT1A1 allozymes were bacterially expressed and affinity-purified. Purified SULT1A1 allozymes were analyzed for sulfation activity using an established assay procedure.ResultsCompared with the wild-type enzyme, SULT1A1 allozymes were shown to display differential sulfating activities toward three analgesic compounds, acetaminophen, O-desmethylnaproxen (O-DMN), and tapentadol, as well as the prototype substrate 4NP.ConclusionResults obtained indicated clearly the impact of genetic polymorphisms on the drug-sulfation activity of SULT1A1 allozymes. Such information may contribute to a better understanding about the differential metabolism of acetaminophen, O-DMN, and tapentadol in individuals with different SULT1A1 genotypes. |
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Keywords: | 4NP 4-nitrophenol PAPS 3’-phosphoadenosine-5’-phosphosulfate SULT cytosolic sulfotransferase SNP single nucleotide polymorphism TLC thin-layer Acetaminophen Tapentadol SULT1A1 Single nucleotide polymorphisms |
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