Glatt Hansruedi, Meinl Walter
Department of Toxicology, German Institute of Human Nutrition (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Potsdam-Rehbrücke, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2004 Jan;369(1):55-68. doi: 10.1007/s00210-003-0826-0. Epub 2003 Nov 5.
Soluble sulfotransferases (SULTs) transfer the sulfo group from the cofactor 5'-phosphoadenosine-3'-phosphosulfate (PAPS) to nucleophilic sites of relatively small acceptor molecules including various hormones and numerous xenobiotics. Sulfo conjugation of xenobiotics can lead to the formation of polar, excretable products as well as reactive, potentially mutagenic and carcinogenic metabolites. Ten SULT genes encoding 11 proteins have been identified in the human. They differ in substrate specificity and tissue distribution. Genetic polymorphisms have been detected in all human SULT genes. The functional significance of any polymorphisms that do not affect the amino acid sequence has not yet been studied. Non-synonymous single-nucleotide exchanges have been observed in SULT1A1, 1A2, 1B1, 1C1, 1C2 and 2A1. Functional consequences have primarily been explored using cDNA-expressed alloenzymes. Furthermore, an Arg213His polymorphism in SULT1A1 has a strong influence on the level of enzyme protein and activity in platelets, which have been widely used for phenotyping. Compared to other xenobiotic-metabolizing enzymes, only few studies have been conducted on associations of SULT genotypes with diseases and other health-related parameters. Statistically significant associations were observed between the SULT1A1 genotype (Arg213His) and age, obesity and certain neoplasias (mammary, pulmonary, esophageal and urothelial cancer). However, these findings require corroboration and specification. The association with neoplasias appears to be complex and varies between subgroups. This is not surprising, as SULTs are involved in the activation of some carcinogens, in the inactivation of other carcinogens, and the regulation of many hormones. It is important to study these functions of SULTs in more detail and to take into account the corresponding environmental and endogenous exposures in epidemiological studies.
可溶性磺基转移酶（SULTs）将辅因子5'-磷酸腺苷-3'-磷酸硫酸酯（PAPS）中的磺基转移至相对较小的受体分子的亲核位点，这些受体分子包括各种激素和众多外源性物质。外源性物质的磺基结合可导致形成极性的、可排泄的产物以及具有反应活性的、潜在诱变和致癌的代谢物。已在人类中鉴定出10个编码11种蛋白质的SULT基因。它们在底物特异性和组织分布上存在差异。在所有人类SULT基因中均检测到基因多态性。尚未对任何不影响氨基酸序列的多态性的功能意义进行研究。在SULT1A1、1A2、1B1、1C1、1C2和2A1中观察到非同义单核苷酸交换。主要使用cDNA表达的同工酶来探究其功能后果。此外，SULT1A1中的Arg213His多态性对血小板中酶蛋白水平和活性有强烈影响，血小板已广泛用于表型分析。与其他外源性物质代谢酶相比，关于SULT基因型与疾病及其他健康相关参数的关联的研究较少。在SULT1A1基因型（Arg213His）与年龄、肥胖症和某些肿瘤（乳腺癌、肺癌、食管癌和尿路上皮癌）之间观察到具有统计学意义的关联。然而，这些发现需要进一步证实和明确。与肿瘤的关联似乎很复杂，且在亚组之间有所不同。这并不奇怪，因为SULTs参与某些致癌物的激活、其他致癌物的失活以及多种激素调节。更详细地研究SULTs的这些功能，并在流行病学研究中考虑相应的环境和内源性暴露，这很重要。
