Sulfotransferases

Jakoby, William B.; Sekura, Ronald D.; Lyon, Ellen Sue; Marcus, Carol J.; Wang, Jun-Lan

doi:10.1016/b978-0-12-380002-2.50017-8

Cited by 63 publications

(35 citation statements)

References 73 publications

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“…The cytosolic enzymes also play an important role in the second-phase metabolism of xenochemicals such as therapeutic drugs, synthetic and naturally occurring toxins, and carcinogens. Since the sulfated metabolites are readily eliminated, the sulfation can be considered to be a cellular defense mechanism against toxicity and/or carcinogenicity of xenochemicals (12). In some cases, however, procarcinogenic and protoxic xenochemicals are sulfated to form active metabolites that attack macromolecules such as DNA (13).…”

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confidence: 99%

Structure and Function of Sulfotransferases

Negishi

Pedersen

Petrotchenko

et al. 2001

Archives of Biochemistry and Biophysics

307

231

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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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mentioning

confidence: 99%

Structure and Function of Sulfotransferases

Negishi

Pedersen

Petrotchenko

et al. 2001

Archives of Biochemistry and Biophysics

307

231

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“…In terms of steroids, hydroxyl groups at positions 3, 21, and 17 of the steroid nucleus are the most common locations for sulfoconjugation (Strott 1996). With the addition of the sulfate group, the polarity of the steroid conjugate is greatly enhanced, causing an increase in water solubility (Jakoby et al 1980). Therefore, sulfoconjugation of hydroxysteroids has been regarded as a major mechanism for their metabolism and excretion (Strott 2002).…”

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confidence: 99%

Molecular cloning and regulation of porcine SULT2A1: relationship between SULT2A1 expression and sulfoconjugation of androstenone

Sinclair

Gilmore²,

Lin³

et al. 2006

Journal of Molecular Endocrinology

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Hydroxysteroid sulfotransferase (SULT2A1) is a key enzyme in the testicular and hepatic metabolism of 5 -androstenone, which is a major component of the off-odor and off-flavor in pork known as boar taint. The goals of this study were to determine the role of testicular and hepatic SULT2A1 activity on plasma 5 -androstenone sulfate levels, the accumulation of 5 -androstenone in adipose tissue, and to gain insight into the regulatory control of SULT2A1. Testicular SULT2A1 activity was negatively correlated (r= −0·57; P,0·01) with 5 -androstenone concentrations in fat. The differences observed in SULT2A1 activity warranted investigation into potential genetic variation within porcine SULT2A1. The cDNA sequence of porcine Sult2A1 was determined to be .82% homologous to the human, mouse, and rat Sult2A1 genes. A single nucleotide polymorphism was detected within the coding region of the Sult2A1 from individual testes and liver samples; however, this did not affect the amino acid sequence of the enzyme. Western blot analysis determined that animals with high concentrations of 5 -androstenone in fat and low SULT2A1 activity had corresponding low levels of SULT2A1 protein compared with animals with low levels of 5 -androstenone in fat. Real-time PCR analysis indicated that Sult2A1 mRNA was increased 2·8-fold in animals with high levels of the protein relative to animals with low levels of the protein. Furthermore, we demonstrated the positive role of the nuclear receptors constitutive androstane receptor and pregnane X receptor, as well as the possible role of farnesoid X receptor in the regulation of testicular SULT2A1 activity. Together, the results of this study suggest that differences in SULT2A1 expression can influence 5 -androstenone accumulation in fat.

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“…The DHEA ST purified in this study is likely to correspond to hydroxysteroid ST I, as classified by Jakoby et al [41], since it was contained within the earliest eluting peak of DHEA ST activity recovered from the DEAE-Sepharose column (not shown) and therefore is also likely to represent the cDNA (STa) isolated by Ogura et al [13]. It is possible that the enzyme purified here corresponds to the androsterone ST purified recently by Matsui's group [lo], since our antibody preparation strongly inhibited the sulfation of androsterone.…”

Section: Discussionmentioning

confidence: 98%

“…It is possible that the enzyme purified here corresponds to the androsterone ST purified recently by Matsui's group [lo], since our antibody preparation strongly inhibited the sulfation of androsterone. The substrate specificity of this enzyme is not limited to DHEA, since it has also been reported that it can sulfate testosterone, P-estradiol, certain alcohols such as isoamyl alcohol [41], and it has been implicated in the bioactivation of methylated polycyclic aromatic hydrocarbons [B].…”

Section: Discussionmentioning

confidence: 99%

Immunochemical characterisation of a dehydroepiandrosterone sulfotransferase in rats and humans

Sharp

Barker

Coughtrie

et al. 1993

European Journal of Biochemistry

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A member of the rat liver hydroxysteroid sulfotransferase (ST) enzyme family metabolising dehydroepiandrosterone (DHEA) was purified from female rats and used to raise rabbit polyclonal antibodies. Characterisation of this antibody preparation demonstrated that it was specific for DHEA ST, and recognised a single 30-kDa protein on immunoblot analysis of rat liver cytosol which was expressed preferentially in female rat liver, and immunohistochemical localisation of the protein in female rat liver determined that DHEA ST was distributed homogeneously in the cytoplasm of hepatocytes. Examination of the extrahepatic expression of this protein showed it to be located predominantly in the liver, although a small amount of enzyme activity was found in the kidney which was not apparently subject to the same sex difference as the hepatic activity. Immunological analysis suggested that this activity was not due to the action of DHEA ST, but to another, unidentified ST isozyme. The antibody cross-reacted strongly with adult human liver DHEA ST, recognising a protein of 35 kDa on immunoblotting. Using this antibody preparation, the distribution of DHEA ST in mid-trimester human fetal tissues was examined, and it was shown that the enzyme is expressed in the adrenal and liver, but not to any significant extent in the kidney or lung. This antibody therefore provides a powerful tool for investigating the function of DHEA ST.Sulfation is an important pathway of metabolism for a host of xenobiotics (e.g. drugs, carcinogens, environmental chemicals) and endogenous compounds (e.g. steroid hormones, bile acids, neurotransmitters and small peptides j, which in general (though not always) reduces the biological activity of compounds through the attachment of a polar sulfate group to various hydroxyl and amine groups [l, 21. These reactions are catalysed by a family of sulfotransferase isozymes (ST), present in the cytosolic fraction of the liver and other tissues. In rats, a number of subfamilies of ST have been discovered, which exhibit enzyme activities towards different classes of substrate, including phenol ST, hydroxysteroid ST and estrone ST, and it is believed, based on protein-purification experiments and the sex differences in the expression of the different activities, that each of these subfamilies comprises a number of different ST enzymes with distinct but overlapping substrate specificities Abbreviations. DHEA, dehydroepiandrosterone ; DHEA-S, dehydroepiandrosterone sulfate ; ST, sulfotransferase; PAdoPS, 3'-phosphoadenosine 5'-phosphosulfate; FITC, fluorescein isothiocyanate; PAdoP, adenosine 3',5'-diphosphate. Dehydroepiandrosterone (DHEA) is an important steroid hormone, and its sulfate ester (DHEA-S) is the major circulating steroid. The exact physiological role(s) of DHEA (and DHEA-S) still remains unclear, although it has been established that DHEA-S is a good substrate for steroid biosynthesis [18-201, and much speculation has appeared regarding the observed anticancer [21], anti-obesity [22] and antidiabetic [2...

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Sulfotransferases

Cited by 63 publications

References 73 publications

Structure and Function of Sulfotransferases

Structure and Function of Sulfotransferases

Molecular cloning and regulation of porcine SULT2A1: relationship between SULT2A1 expression and sulfoconjugation of androstenone

Immunochemical characterisation of a dehydroepiandrosterone sulfotransferase in rats and humans

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