Coughtrie M W H
Department of Molecular & Cellular Pathology, University of Dundee, Ninewells Hospital & Medical School, Dundee, Scotland, UK.
Pharmacogenomics J. 2002;2(5):297-308. doi: 10.1038/sj.tpj.6500117.
Members of the cytosolic sulfotransferase (SULT) superfamily catalyse the sulfation of a multitude of xenobiotics, hormones and neurotransmitters. Humans have at least 10 functional SULT genes, and a number of recent advances reviewed here have furthered our understanding of SULT function. Analysis of expression patterns has shown that sulfotransferases are highly expressed in the fetus, and SULTs may in fact be a major detoxification enzyme system in the developing human. The X-ray crystal structures of three SULTs have been solved and combined with mutagenesis experiments and molecular modelling, they have provided the first clues as to the factors that govern the unique substrate specificities of some of these enzymes. In the future these and other studies will facilitate prediction of the fate of chemicals metabolised by sulfation. Variation in sulfation capacity may be important in determining an individual's response to xenobiotics, and there has been an explosion in information on sulfotransferase polymorphisms and their functional consequences, including the influence of SULT1A1 genotype on susceptibility to colorectal and breast cancer. Finally, the first gene knockout experiments with SULTs have recently been described, with the generation of estrogen sulfotransferase deficient mice in which reproductive capacity is compromised. Our improved understanding of these enzymes will have significant benefits in such diverse areas as drug design and development, cancer susceptibility, reproduction and development.
胞质磺基转移酶（SULT）超家族的成员催化多种外源性物质、激素和神经递质的硫酸化反应。人类至少有10个功能性SULT基因，本文综述的一些最新进展加深了我们对SULT功能的理解。对表达模式的分析表明，磺基转移酶在胎儿中高度表达，事实上SULTs可能是发育中的人类主要的解毒酶系统。三种SULT的X射线晶体结构已被解析，结合诱变实验和分子建模，它们为一些酶独特底物特异性的决定因素提供了初步线索。未来，这些研究及其他研究将有助于预测经硫酸化代谢的化学物质的命运。硫酸化能力的差异可能对确定个体对外源性物质的反应很重要，关于磺基转移酶多态性及其功能后果的信息激增，包括SULT1A1基因型对结直肠癌和乳腺癌易感性的影响。最后，最近描述了首次使用SULTs的基因敲除实验，培育出了雌激素磺基转移酶缺陷型小鼠，其生殖能力受到损害。我们对这些酶的深入理解将在药物设计与开发、癌症易感性、生殖和发育等多个领域带来显著益处。
