Sulfotransferase (SULT) 1A1 Polymorphic Variants *1, *2, and *3 Are Associated with Altered Enzymatic Activity, Cellular Phenotype, and Protein Degradation

Nagar, Swati; Walther, Susan E.; Blanchard, Rebecca

doi:10.1124/mol.105.019240

Cited by 133 publications

(101 citation statements)

References 37 publications

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“…It has been reported that SULT1A1 recombinant allozymes have variable thermal stability and spe- cific activity toward p-nitrophenol, catechol estrogens, and dietary flavonoids (31,47,48). The SULT1A1*2 variant was associated with low enzyme activity and thermal stability (45,47,48). Although SULT1A1*3 had compatible thermal stability to wild type enzyme, its specific activities for SULT1A1 substrates were usually lower than that of wild type (48).…”

Section: Discussionmentioning

confidence: 99%

“…The SULT1A1*2 variant was associated with low enzyme activity and thermal stability (45,47,48). Although SULT1A1*3 had compatible thermal stability to wild type enzyme, its specific activities for SULT1A1 substrates were usually lower than that of wild type (48).…”

Section: Discussionmentioning

confidence: 99%

“…Despite the low frequency of SULT1A1*3 in Caucasians, it has an allelic frequency of 0.229 in African Americans (46). It has been reported that SULT1A1 recombinant allozymes have variable thermal stability and spe- cific activity toward p-nitrophenol, catechol estrogens, and dietary flavonoids (31,47,48). The SULT1A1*2 variant was associated with low enzyme activity and thermal stability (45,47,48).…”

Section: Discussionmentioning

confidence: 99%

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Detoxication of Benzo[a]pyrene-7,8-dione by Sulfotransferases (SULTs) in Human Lung Cells

Zhang

Huang

Blair

et al. 2012

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Detoxication of Benzo[a]pyrene-7,8-dione by Sulfotransferases (SULTs) in Human Lung Cells

Zhang

Huang

Blair

et al. 2012

Journal of Biological Chemistry

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“…It has been repeatedly reported that human SULT1A1*2 allele, a SNP in exon 7 of the SULT1A1 gene resulting in the substitution of a histidine for an arginine at position 213 of the translated protein, produces an enzyme with impaired catalytic activity and decreased thermal stability (20,21). Although relatively little has been reported about the functional significance of SULT1A1*3, possibly because of its low allele frequency in Caucasians and Asians, two earlier studies consistently showed that the SULT1A1*3 variant exhibits a higher affinity for the cofactor PAPS than the SULT1A1*1 and SULT1A1*2 variants (21, 34).…”

Section: Discussionmentioning

confidence: 99%

“…19). The allelic variants of SULT1A1 have been associated with altered enzyme activity and thermal stability of the enzyme, with the SULT1A1*2 allele being associated with low enzyme activity and thermal stability (20,21).…”

Section: Introductionmentioning

confidence: 99%

Association of Human Cytochrome P450 1A1 (CYP1A1) and Sulfotransferase 1A1 (SULT1A1) Polymorphisms with Differential Metabolism and Cytotoxicity of Aminoflavone

Zheng

Sha

Liu

et al. 2010

Molecular Cancer Therapeutics

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Aminoflavone (AF), a clinically investigational novel anticancer agent, requires sequential metabolic activation by CYP1A1 and SULT1A1 to exert its antitumor activities. The purpose of this study was to determine the functional significance of common polymorphisms of human CYP1A1 and SULT1A1 on the metabolism and cytotoxicity of AF. To this end, Chinese Hamster V79 cells were genetically engineered to stably express human CYP1A1*1 (wild-type), CYP1A1*2C (I462V), or CYP1A1*4 (T461N) and coexpress human CYP1A1*1 with human SULT1A1*1 (wild-type), SULT1A1*2 (R213H), or SULT1A1*3 (M223V). The metabolism and cytotoxicity of AF were evaluated in these cellular models. All common variants of CYP1A1 and SULT1A1 were actively involved in the metabolic activation of AF, but with a varying degree of activity. Whereas CYP1A1 I462V variant exhibited a superior activity (mainly caused by a significantly higher V max ) for hydroxylations of AF, expression of different CYP1A1 variants did not confer cell differential sensitivity to AF. The cells coexpressing CYP1A1*1 with SULT1A1

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Sulfotransferases

Ma¹,

Schrag²

2012

Encyclopedia of Drug Metabolism and Interactions

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The sulfotransferases (SULTs) are a family of phase II enzymes that catalyze the transfer of a sulfonate group (‐SO 3− ) from the cofactor 3′‐phosphoadenosine‐5′‐phosphosulfate (PAPS) to an acceptor molecule or substrate. Since these enzymes can conjugate with a wide variety of xenobiotics and endogenous substrates, they function not only as drug‐metabolizing enzymes but also modulators of physiological activities through conjugations of endogenous molecules such as steroids, catecholamines, and thyroid hormones. This chapter aims to provide drug metabolism scientists with an introductory overview on various aspects of SULTs along with challenges and complications associated with SULT‐mediated biotransformations, particularly encountered during the drug discovery and development process. In recent years, commercially available hepatocyte preparations and recombinant SULT enzymes facilitate the determination of SULT involvement for compounds of interest. However, significant challenges do remain. For example, when conducting reaction‐phenotyping experiments for SULT‐catalyzed conjugations, there is currently a lack of well‐characterized isoform‐specific probe substrates and inhibitors, in addition to a lack of well‐established in vitro incubation conditions. Kinetic experiments, too, often require careful interpretation, as profound substrate inhibition is rather common for sulfation reactions. From the toxicology stand‐point, sulfation may pose liability concerns due to the potential formation of reactive electron‐deficient metabolite species. It is recommended that investigators should take the time to explore and understand the properties of SULT‐mediated conjugations and their implications.

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Sulfotransferase (SULT) 1A1 Polymorphic Variants ^1, ^2, and ^*3 Are Associated with Altered Enzymatic Activity, Cellular Phenotype, and Protein Degradation

Abstract: The superfamily of sulfotransferase (SULT) enzymes catalyzes the sulfate conjugation of several pharmacologically important endo-and xenobiotics.

Cited by 133 publications

References 37 publications

Detoxication of Benzo[a]pyrene-7,8-dione by Sulfotransferases (SULTs) in Human Lung Cells

Detoxication of Benzo[a]pyrene-7,8-dione by Sulfotransferases (SULTs) in Human Lung Cells

Association of Human Cytochrome P450 1A1 (CYP1A1) and Sulfotransferase 1A1 (SULT1A1) Polymorphisms with Differential Metabolism and Cytotoxicity of Aminoflavone

Sulfotransferases

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