Sulfation of catecholamines and serotonin by SULT1A3 allozymes

Abstract

Previous studies have demonstrated the involvement of sulfoconjugation in the metabolism of catecholamines and serotonin. The current study aimed to clarify the effects of single nucleotide polymorphisms (SNPs) of human SULT1A3 and SULT1A4 genes on the enzymatic characteristics of the sulfation of dopamine, epinephrine, norepinephrine and serotonin by SULT1A3 allozymes. Following a comprehensive search of different SULT1A3 and SULT1A4 genotypes, twelve non-synonymous (missense) coding SNPs (cSNPs) of SULT1A3/SULT1A4 were identified. cDNAs encoding the corresponding SULT1A3 allozymes, packaged in pGEX-2T vector were generated by site-directed mutagenesis. SULT1A3 allozymes were expressed, and purified. Purified SULT1A3 allozymes exhibited differential sulfating activity toward catecholamines and serotonin. Kinetic analyses demonstrated differences in both substrate affinity and catalytic efficiency of the SULT1A3 allozymes. Collectively, these findings provide useful information relevant to the differential metabolism of dopamine, epinephrine, norepinephrine and serotonin through sulfoconjugation in individuals having different SULT1A3/SULT1A4 genotypes.

Ontogeny of Hepatic Sulfotransferases and Prediction of Age-Dependent Fractional Contribution of Sulfation in Acetaminophen Metabolism

“…For example, SULT1A1 is involved in the biotransformation of acetaminophen, minoxidil, 4-hydroxytamoxifen, oxymorphone, nalbuphine, nalorphine, naltrexone, isoflavones, estradiol, and iodothyronines (Coughtrie et al, 1994;Nishiyama et al, 2002;Nowell and Falany, 2006;Kurogi et al, 2014;Marto et al, 2017). Likewise, SULT1A3 is known to metabolize catecholamines, serotonin, salbutamol, ritodrine, and troglitazone (Eisenhofer et al, 1999;Honma et al, 2002;Hui and Liu, 2015;Bairam et al, 2018); SULT1B1 plays a role in elimination of iodothyronines, thyroxine, and 1-naphthol (Fujita et al, 1997;Wang et al, 1998;Gamage et al, 2006); SULT1E1 metabolizes raloxifene and estrogens (Falany et al, 1995;Schrag et al, 2004Schrag et al, , 2006Cubitt et al, 2011); and SULT2A1 assists in metabolism of ciprofloxacin, desipramine, metoclopramide, dehydroepiandrosterone (DHEA), several bile acids, and 25-hydroxyvitamin D 3 (Falany et al, 1994;Meloche et al, 2002Meloche et al, , 2004Cook et al, 2009;Nakamura et al, 2009;Senggunprai et al, 2009;Huang et al, 2010;Wong et al, 2018). Because several of these substrates are s This article has supplemental material available at dmd.aspetjournals.org.…”

Impact of SULT1A3/SULT1A4 genetic polymorphisms on the sulfation of phenylephrine and salbutamol by human SULT1A3 allozymes

“…Previous studies have revealed that the gene coding for SULT1A3 had undergone duplication during the evolutionary process generating two genes, designated SULT1A3 and SULT1A4, that encode identical protein products, collectively called SULT1A3 [18]. We recently employed site-directed mutagenesis in conjunction with bacterial expression and affinity purification to prepare twelve distinct SULT1A3 allozymes [21]. In this study, the twelve SULT1A3 allozymes, in comparison with the wild-type enzyme, were investigated for their sulfating activity toward phenylephrine and salbutamol.…”

“…Wild-type and SULT1A3 allozymes were generated, expressed, and purified to greater than 95% homogeneity as previously reported [21].…”

Investigating the Mechanism of Trimethoprim-Induced Skin Rash and Liver Injury

“…Recombinant hSULTs (SULT1A1, SULT1A2, SULT1A3, SULT1B1, SULT1C2 SULT1C3, SULT1C4, SULT1E1, SULT2A1, SULT2B1a, SULT2B1b, SULT4A1, and SULT6B1), expressed using pGEX-2TK or pET23c prokaryotic expression system, were prepared as described previously ( Pai et al , 2002 ; Sakakibara et al , 2002 ; Suiko et al , 2000 ). The sulfating activity of purified recombinant hSULTs toward TMP-OH was assayed based on a previously established procedure ( Bairam et al , 2018 ), with radioactive PAP[ 35 S] as the sulfate donor. The assay mixture, following a 15 min reaction at 37°C, was separated by TLC and analyzed for [ 35 S]sulfated TMP-OH.…”