Human gastrointestinal sulfotransferases: identification and distribution☆

doi:10.1016/S0041-008X(02)00073-X

Toxicology and Applied Pharmacology

Volume 187, Issue 3, 15 March 2003, Pages 186-197

https://doi.org/10.1016/S0041-008X(02)00073-X Get rights and content

Abstract

Sulfotransferases (STs) catalyze the sulfation of many structurally diverse molecules. Enzymatic assays and Western blots have been used to identify and characterize STs in the human gastrointestinal tract. Sulfation activities for 2-naphthol, dopamine, estradiol, and dehydroepiandrosterone (DHEA) from 23 donors were measured in cytosol prepared from stomach, duodenum, segments of small intestine, and colon and were compared to levels in human liver cytosol. Stomach and colon had low 2-naphthol and dopamine sulfation activities and almost no estradiol and DHEA sulfation activity. For all four substrates, small intestine has higher activities than both stomach and colon. Human small intestine 2-naphthol sulfation specific activity is approximately half that of human liver. Human small intestine dopamine sulfation activity is three times as high as that of human liver. While estrogen sulfation activity is about the same for both human intestine and human liver, human liver DHEA sulfation activity is about five times as high as that of human small intestine. The distribution of ST activities along the length of the small intestine was very different among different donors. Some donors had higher activity in the proximal segments of the small intestine, whereas other donors had higher activity in the distal segments of the small intestine. Our results also demonstrated high variation of small intestine sulfation activities compared with human liver activities among different donors. The Western blot results agreed with the enzymatic assay results. These results suggest that xenobiotics may regulate human small intestinal STs.

Section snippets

Materials

[2,4,6,7-³H(N)]Estradiol ([³H]E₂, 72Ci/mmol) and [1,2,6,7,-³H(N)]dehydroepiandrosterone ([³H]DHEA, 60Ci/mmol) were purchased from NEN (Boston, MA). 2-Naphthol, dopamine, and PAPS were purchased from Sigma Chemical Co (St. Louis, MO). SuperSignal West Femto Maximum Sensitive Substrate for Western blotting was purchased from Pierce (Rockford, IL). Anti-rabbit IgG horseradish peroxidase secondary antibody was obtained from Gentest (Woburn, MA). NuPAGE Bis–Tris and Tricine gels were from Novex (San

Results

At least four human STs have been relatively well characterized. These include two phenol STs, simple phenol-sulfating ST (P-PST or SULT1A1) and M-PST or SULT1A3; EST or SULT1E1; and hydroxysteroid ST (DHEA-ST or SULT2A1). P-PST is the phenol ST that has high activity for simple phenols Falany et al 1990, Heroux et al 1989. While M-PST also has activity for simple phenolic molecules, it has high specific activity for some monoamines, such as dopamine, which distinguishes M-PST from P-PST, the

Discussion

The results presented here demonstrate that human small intestine has ST activities comparable to those of human liver and that these activities are located mainly in the small intestine. Human liver cytosols have higher P-PST and DHEA-ST specific activity than human intestine. Human liver cytosols and human intestine cytosols have about the same specific activity for EST. In contrast, human intestine cytosols have much higher dopamine sulfation activities than human liver cytosols. Human

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^☆: This investigation was supported in part by NIH Grants GM59873 (G.C.), DK51971, DK49715, and DK56226 (A.R.P.).

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Regular articleHuman gastrointestinal sulfotransferases: identification and distribution☆☆

Abstract

Section snippets

Materials

Results

Discussion

Biochem. Biophys. Res. Commun.

Brain Res. Bull.

Mol. Cell. Endocrinol.

J. Virol. Methods

J. Steroid Biochem. Mol. Biol.

Arch. Biochem. Biophys.

J. Steroid Biochem. Mol. Biol.

Environ. Toxicol. Pharmacol.

J. Biol. Chem.

J. Steroid Biochem. Mol. Biol.

Anal. Biochem.

Steroids

Biochim. Biophys. Acta

J. Steroid Biochem. Mol. Biol.

J. Steroid Biochem.

Mar. Environ. Res.

Biochem. Pharmacol.

Differential distribution of phenol and catechol sulphotransferases in human liver and intestinal mucosa

Pharmacology

Enzyme- and sex-specific differences in the intralobular localizations and distributions of aryl sulfotransferase IV (tyrosine-ester sulfotransferase) and alcohol (hydroxysteroid) sulfotransferase a in rat liver

Drug Metab. Disp.

Photoaffinity labeling probe for the substrate binding site of human phenol sulfotransferase (SULT1A1)7-azido-4-methylcoumarin

Prot. Sci.

Immunological characterization of dehydroepiandrosterone sulfotransferase from human liver and adrenal

Mol. Pharmacol.

Regular article
Human gastrointestinal sulfotransferases: identification and distribution☆☆