Molecular and Cellular PharmacologyHuman phenol sulfotransferases SULT1A2 and SULT1A1: Genetic polymorphisms, allozyme properties, and human liver genotype–phenotype correlations
Section snippets
Human liver biopsy samples
Human hepatic “surgical waste” tissue was obtained from 61 Caucasian patients undergoing clinically indicated hepatectomies or open hepatic biopsies and was stored at −80°. All tissue samples were obtained under guidelines approved by the Mayo Clinic Institutional Review Board. These frozen hepatic tissue samples were homogenized and centrifuged at 100,000 g for 1 hr as described previously [9] to obtain high-speed supernatant (HSS) preparations.
PST enzyme activity, thermal stability, and inhibitor sensitivity
TS PST enzyme activity was measured by the method
Human liver TS PST phenotype
Population and family studies had demonstrated previously that levels of TS PST thermal stability and activity in the platelet, measured under optimal conditions with 4 μM 4-nitrophenol as substrate, were controlled by common genetic polymorphisms 13, 14(Fig. 1). Because human platelet TS PST activity and thermal stability were reported to be correlated with hepatic TS PST activity and thermal stability [36], our initial experiment involved the measurement of both of these variables under
Discussion
We recently reported a series of alleles for SULT1A1, one of which, SULT1A1∗2, was associated consistently with significantly decreased levels of both TS PST activity and thermal stability in the blood platelet [16](Fig. 1). The present experiments were conducted to determine whether SULT1A2, like SULT1A1, might also have a series of alleles and allozymes, to compare the properties of all common SULT1A1 and 1A2 allozymes and to study phenol SULT genotype–phenotype correlations in an important
Acknowledgements
We thank Diane Otterness for her advice and Luanne Wussow for her assistance with the preparation of this manuscript. This work was supported, in part, by NIH Grants RO1 GM35720 (R. M. W.) and RO1 GM28157 (R. M. W.) and by NRSA Individual Postdoctoral Fellowship GM18800 (R. B. R.).
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2023, Journal of Asian Natural Products ResearchEffects of the human SULT1A1 polymorphisms on the sulfation of acetaminophen,O-desmethylnaproxen, and tapentadol
2019, Pharmacological ReportsCitation Excerpt :Studies have shown that genetic variability in the genes encoding enzymes, including SULTs, responsible for the metabolism of acetaminophen may be associated with risk of certain individuals for acetaminophen-induced toxicity [16,42,43]. It is noted that single nucleotide polymorphisms (SNPs) of the SULT1A1 gene have been reported [22,23]. Earlier studies using platelet samples collected from human subjects with different SULT1A1 genotypes showed greater than 50-fold variations in their sulfation activity toward 4-nitrophenol, a prototype substrate for SULT1A1 [22].
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2018, Comprehensive Toxicology: Third EditionRelationship of SULT1A1 copy number variation with estrogen metabolism and human health
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Present address: Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, PA 19111.