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人脱氢表雄酮硫酸转移酶。纯化、分子克隆及特性分析。

Human dehydroepiandrosterone sulfotransferase. Purification, molecular cloning, and characterization.

作者信息

Falany C N, Comer K A, Dooley T P, Glatt H

机构信息

Department of Pharmacology and Toxicology, University of Alabama at Birmingham 35294, USA.

出版信息

Ann N Y Acad Sci. 1995 Dec 29;774:59-72. doi: 10.1111/j.1749-6632.1995.tb17372.x.

DOI:10.1111/j.1749-6632.1995.tb17372.x
PMID:8597484
Abstract

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.

摘要

人体组织至少拥有四种不同形式的胞质硫酸转移酶(ST),其中三种参与类固醇的硫酸化作用。硫酸脱氢表雄酮硫酸转移酶(DHEA - ST)负责人体组织中大部分羟基类固醇和胆汁酸的硫酸化,人体肝脏和肾上腺组织中存在大量该酶。在成年人体肾上腺中,DHEA - ST已通过免疫定位到肾上腺皮质的网状带。尚未有关于成年人体肝脏胞质中DHEA - ST活性表达存在年龄或性别相关差异的报道。编码DHEA - ST的cDNA已从人肝脏cDNA文库中分离出来,并在哺乳动物COS细胞和大肠杆菌中表达。纯化和分子特性研究表明人体组织中DHEA - ST为单一形式。在哺乳动物或细菌细胞中表达的DHEA - ST的特性与天然酶非常相似。DHEA - ST还可将多种前致癌物生物活化为具有反应活性的亲电形式。羟甲基多环芳烃可被DHEA - ST以相对较快的速度硫酸化并生物活化,而1'-羟基黄樟素和N -羟基 - 2 -乙酰氨基芴的生物活化程度较低。

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