Pharmacogenetics of Sulfotransferase

Nagata, Kiyoshi; Yamazoe, Yasushi

doi:10.1146/annurev.pharmtox.40.1.159

Cited by 198 publications

(125 citation statements)

References 87 publications

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“…SULT1A1 bioactivates and detoxifies endogenous and exogenous compounds such as phenolic xenobiotics, iodothyronines and hydroxylated aromatic amines. [2][3][4]6 The precise way that SULT1A1 influences cancer development and whether certain SULT1A1 genotypes predispose to cancer are not clear at this time. 5,6,[12][13][14][15] In an in vitro study, Glatt et al 12 found that promutagens such as 2-nitropropane were more efficiently activated by the arg allele than by the his allele in the Salmonella or V79 system.…”

Section: Discussionmentioning

confidence: 99%

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SULT1A1 polymorphism and esophageal cancer in males

Wang

et al. 2002

Intl Journal of Cancer

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Sulfotransferase (SULT) 1A1 detoxifies and bioactivates a broad spectrum of substrates including xenobiotics. It has been suggested that the SULT1A1 his (histidine) allele, which is caused by a his for arg (arginine) substitution due to a G3 A transition at codon 213, carries a significantly higher risk for women to develop breast cancer. We investigated the association between the SULT1A1 arg/his genotype and esophageal cancer in men, 187 cases of esophageal squamous cell carcinoma and 308 controls from 3 medical centers in Taiwan. Cigarette smoking, areca chewing and alcohol consumption were the major risks for developing esophageal cancer. The frequencies of arg/his in cases and controls were 27.8% (52/187) and 11.0% (34/308), respectively (p < 0.0001). No subjects carried his/his. After adjusting for substance use and other covariates, individuals with arg/his had a 3.53-fold higher risk (95% CI ‫؍‬ 2.12-5.87) of developing esophageal cancer than those with arg/arg. Unexpectedly, this positive association was found to be even stronger (adjusted OR ‫؍‬ 4.04 -4.80) among non-smokers, non-drinkers or non-chewers. Our findings suggest that the SULT1A1 his 213 allele is important in the development of esophageal cancer in men.

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Section: Discussionmentioning

confidence: 99%

“…[1][2][3] There are at least 7 human SULT isoforms, 3 and 1 of them, SULT1A1, metabolizes or bioactivates a broad range of substrates, including phenolic xenobiotics, iodothyronines and hydroxylated aromatic amines. 4 -6 The SULT1A1 gene that encodes the SULT1A1 enzyme has been mapped to chromosome 16p12.1-p11.2; its entire sequence has been determined.…”

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confidence: 99%

SULT1A1 polymorphism and esophageal cancer in males

Wang

et al. 2002

Intl Journal of Cancer

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“…However, extensive gene sequencing studies 81 failed to identify the variant alleles represented by these cDNAs. These authors did report two cSNPs (Met 57 Thr, Glu 186 Val) with allele frequencies around 3% which have been assigned the preliminary designation * 2 and * 3, respectively, 82 ( Table 2). The SULT2A1 * 2 and * 3 allozymes showed decreased enzyme activity when expressed in COS cells.…”

Section: Sult Families 2 Andmentioning

confidence: 99%

Sulfation through the looking glass—recent advances in sulfotransferase research for the curious

2002

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Members of the cytosolic sulfotransferase (SULT) superfamily catalyse the sulfation of a multitude of xenobiotics, hormones and neurotransmitters. Humans have at least 10 functional SULT genes, and a number of recent advances reviewed here have furthered our understanding of SULT function. Analysis of expression patterns has shown that sulfotransferases are highly expressed in the fetus, and SULTs may in fact be a major detoxification enzyme system in the developing human. The X-ray crystal structures of three SULTs have been solved and combined with mutagenesis experiments and molecular modelling, they have provided the first clues as to the factors that govern the unique substrate specificities of some of these enzymes. In the future these and other studies will facilitate prediction of the fate of chemicals metabolised by sulfation. Variation in sulfation capacity may be important in determining an individual's response to xenobiotics, and there has been an explosion in information on sulfotransferase polymorphisms and their functional consequences, including the influence of SULT1A1 genotype on susceptibility to colorectal and breast cancer. Finally, the first gene knockout experiments with SULTs have recently been described, with the generation of estrogen sulfotransferase deficient mice in which reproductive capacity is compromised. Our improved understanding of these enzymes will have significant benefits in such diverse areas as drug design and development, cancer susceptibility, reproduction and development.

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“…Since the late 1980s, nearly a hundred ST cDNAs have been cloned, including cytosolic and membrane enzymes (5,14). One difficulty soon realized was the lack of overall amino acid sequence homology between the cytosolic and membrane STs.…”

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confidence: 99%

Structure and Function of Sulfotransferases

Negishi

Pedersen

Petrotchenko

et al. 2001

Archives of Biochemistry and Biophysics

307

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Sulfotransferases (STs) catalyze the transfer reaction of the sulfate group from the ubiquitous donor 3 -phosphoadenosine 5 -phosphosulfate (PAPS) to an acceptor group of numerous substrates. This reaction, often referred to as sulfuryl transfer, sulfation, or sulfonation, is widely observed from bacteria to humans and plays a key role in various biological processes such as cell communication, growth and development, and defense. The cytosolic STs sulfate small molecules such as steroids, bioamines, and therapeutic drugs, while the Golgi-membrane counterparts sulfate large molecules including glucosaminylglycans and proteins. We have now solved the X-ray crystal structures of four cytosolic and one membrane ST. All five STs are globular proteins composed of a single ␣/␤ domain with the characteristic five-stranded ␤-sheet. The ␤-sheet constitutes the core of the Paps-binding and catalytic sites. Structural analysis of the PAPS-, PAP-, substrate-, and/or orthovanadate (VO 4 3؊ )-bound enzymes has also revealed the common molecular mechanism of the transfer reaction catalyzed by sulfotransferses. The X-ray crystal structures have opened a new era for the study of sulfotransferases.

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Pharmacogenetics of Sulfotransferase

Cited by 198 publications

References 87 publications

SULT1A1 polymorphism and esophageal cancer in males

SULT1A1 polymorphism and esophageal cancer in males

Sulfation through the looking glass—recent advances in sulfotransferase research for the curious

Structure and Function of Sulfotransferases

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