Very important pharmacogene summary: sulfotransferase 1A1

Abstract

Cytosolic sulfotransferase 1A subfamily members catalyze the sulfate conjugation of phenolic compounds including steroid hormones, catecholamines, and phenolic drugs and also participate in the bioactivation of procarcinogens (reviewed in Ref.[1]). The endogenous cosubstrate 3 0 -phosphoadenosine 5 0 -phosphate (PAPS) acts as the sulfate donor. Sulfotransferase 1A1 (SULT1A1) metabolizes several phenolic substrates including simple phenolic compounds (4-nitrophenol, which is used as a probe substrate, [2]); drugs (acetaminophen [3], minoxidil [4]); estrogens (estrone, B-estradiol [5], 2-hydroxyestrone, 2-hydroxyestradiol, 4-hydroxyestrone, 4-hydroxyestradiol [6]), and synthetic estrogenic compounds (trans-4-hydroxytamoxifen [7], diethylstilbestrol [5], 2-methoxy estradiol [8]). 2,6-dichloro-4-nitrophenol inhibits SULT1A1 activity [9-11]. SULT1A1 also bioactivates procarcinogens including N-hydroxy metabolites of 2-amino-3-methylimidazo[4,5-f] guinoline [12] and other procarcinogens [1]. The SULT1A1 gene was cloned in 1996 [13] and resides on chromosome 16 in close proximity to the three other members of the SULT1A subfamily: SULT1A2, SULT1A3, and SULT1A4 [14,15]. The gene consists of seven coding exons and two alternatively spliced upstream noncoding exons. The 885-nucleotide open reading frame encodes a 295 amino acid protein. SULT1A1 protein is present in many human tissues, including liver, kidney, and platelets [16].

The Stereoselective Sulfate Conjugation of 4′‐Methoxyfenoterol Stereoisomers by Sulfotransferase Enzymes

“…Previous studies have demonstrated that there is a high interindividual variability in SULT enzyme expression and activity, which has been attributed to both environmental and genetic factors . For example, SULT1A1 exhibits over 50‐fold variations in enzyme activity, associated in part with single nucleotide polymorphisms and copy number variations . Thus, it is important to identify the contributions of the individual SULT isoforms to the sulfation of MF stereoisomers and the potential for pharmacogenetic differences in bioavailability.…”

“…14 For example, SULT1A1 exhibits over 50-fold variations in enzyme activity, associated in part with single nucleotide polymorphisms and copy number variations. 15 Thus, it is important to identify the contributions of the individual SULT isoforms to the sulfation of MF stereoisomers and the potential for pharmacogenetic differences in bioavailability. The data from this study demonstrate that the sulfation of MF stereoisomers is mediated by SULT1A1*1, SULT1A1*2, SULT1A3, and SULT1E1 isoforms.…”

Relationship between Genotypes Sult1a2 and Cyp2d6 and Tamoxifen Metabolism in Breast Cancer Patients

“…Although it has been established that tamoxifen and its metabolites undergo phase II conjugation reactions including glucuronidation and sulfation, few studies have examined the role of phase II sulfotransferase enzymes (SULTs) in TAM metabolism. Given that 4-OH-TAM and endoxifen are known substrates of SULT1A1 [5 and 6, respectively], different SULT enzyme activity levels could markedly influence the efficacy of TAM [5].…”

Richtwerte für Butanonoxim in der Innenraumluft

“…Männliche Ratten weisen eine deutliche höhere Sulfotransferaseaktivität auf als weibliche Ratten und Ratten eine höhe-re als Mäuse [28]. Die Aktivität der humanen Sulfotransferase 1A1 (SULT1A1) variiert um eine Vielfaches zwischen Individuen, bedingt unter anderem durch Einzelnukleotid-Polymorphismen (SNP) und Kopienanzahlvariationen (CNV) [29].…”