Human dehydroepiandrosterone sulfotransferase. Purification, molecular cloning, and characterization.
Human tissues possess at least four distinct forms of cytosolic ST, three of which are involved in the sulfation of steroids. DHEA-ST is responsible for the majority of hydroxysteroid and bile acid sulfation in human tissues and abundant levels of the enzyme are present in human liver and adrenal tissues. In the adult human adrenal, DHEA-ST has been localized immunologically to the zona reticularis of the adrenal cortex. No age- or gender-related differences in the expression of DHEA-ST activity in adult human liver cytosols have been reported. The cDNA encoding DHEA-ST has been isolated from a human liver cDNA library and expressed in both mammalian COS cells and E. coli. Purification and molecular characterization studies suggest a single form of DHEA-ST in human tissues. The properties of DHEA-ST expressed in either mammalian or bacterial cells are very similar to those of the native enzyme. DHEA-ST can also bioactivate a number of procarcinogens to reactive electrophilic forms. Hydroxymethyl PAHs are sulfated and bioactivated at a relatively rapid rate by DHEA-ST, whereas 1'-hydroxysafrole and N-hydroxy-2-acetylaminofluorene are bioactivated to a lesser extent.
Falany
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Department of Pharmacology and Toxicology, University of Alabama at Birmingham 35294, USA.
Comer
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Dooley
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Glatt
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D000311:Adrenal Glands / Q000201:enzymology; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D015239:Arylsulfotransferase / Q000737:chemistry; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate; D006801:Humans; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D051381:Rats; D016415:Sequence Alignment; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D015238:Sulfotransferases; C019998:dehydroepiandrosterone sulfotransferase; D015239:Arylsulfotransferase; C020122:estrone sulfotransferase