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Effects of the human SULT1A1 polymorphisms on the sulfation of acetaminophen, O-desmethylnaproxen, and tapentadol

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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.

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Abbreviations

4NP:

4-nitrophenol

O-DMN:

O-desmethylnaproxen

PAPS:

3’-phosphoadenosine-5’-phosphosulfate

SULT:

cytosolic sulfotransferase

SNP:

single nucleotide polymorphism

TLC:

thin-layer

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Authors and Affiliations

  1. Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH, 43614, USA

    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

  2. Department of Pharmacology, College of Pharmacy, University of Karbala, Karbala, Iraq

    Mohammed I. Rasool

  3. Department of Pharmacology, College of Pharmacy, University of Kufa, Najaf, Iraq

    Ahsan F. Bairam

  4. Biochemistry and Applied Biosciences, University of Miyazaki, Miyazaki, 889-2192, Japan

    Katsuhisa Kurogi

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  1. Mohammed I. Rasool
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  9. Ming-Cheh Liu
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Correspondence to Ming-Cheh Liu.

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Rasool, M.I., Bairam, A.F., Gohal, S.A. et al. Effects of the human SULT1A1 polymorphisms on the sulfation of acetaminophen, O-desmethylnaproxen, and tapentadol. Pharmacol. Rep 71, 257–265 (2019). https://doi.org/10.1016/j.pharep.2018.12.001

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