Mohammed I Rasool1, Ahsan F Bairam2, Saud A Gohal3, Amal A El Daibani3, Fatemah A Alherz3, Maryam S Abunnaja3, Eid S Alatwi3, Katsuhisa Kurogi4, Ming-Cheh Liu5. 1. Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614, USA; Department of Pharmacology, College of Pharmacy, University of Karbala, Karbala, Iraq. 2. Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614, USA; Department of Pharmacology, College of Pharmacy, University of Kufa, Najaf, Iraq. 3. Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614, USA. 4. Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614, USA; Biochemistry and Applied Biosciences, University of Miyazaki, Miyazaki 889-2192, Japan. 5. Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614, USA. Electronic address: ming.liu@utoledo.edu.
Abstract
BACKGROUND: Non-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. METHODS: Human 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. RESULTS: Compared 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. CONCLUSION: Results 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.
BACKGROUND: Non-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 humanSULT1A1 gene on the sulfation of these analgesic compounds by SULT1A1 allozymes. METHODS:HumanSULT1A1 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. RESULTS: Compared 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. CONCLUSION: Results 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.
Authors: S Ozawa; M Shimizu; T Katoh; A Miyajima; Y Ohno; Y Matsumoto; M Fukuoka; Y M Tang; N P Lang; F F Kadlubar Journal: J Biochem Date: 1999-08 Impact factor: 3.387
Authors: Katsuhisa Kurogi; Mohammed I Rasool; Fatemah A Alherz; Amal A El Daibani; Ahsan F Bairam; Maryam S Abunnaja; Shin Yasuda; Lauren J Wilson; Ying Hui; Ming-Cheh Liu Journal: Expert Opin Drug Metab Toxicol Date: 2021-06-30 Impact factor: 4.936
Authors: Raju Dash; Md Chayan Ali; Nayan Dash; Md Abul Kalam Azad; S M Zahid Hosen; Md Abdul Hannan; Il Soo Moon Journal: Int J Mol Sci Date: 2019-12-11 Impact factor: 5.923