Lindsay Julian, Wang Lin-Lin, Li Yong, Zhou Shu-Feng
Division of Pharmacy, School of Life Sciences, Queensland University of Technology, Brisbane, Australia.
Curr Drug Metab. 2008 Feb;9(2):99-105. doi: 10.2174/138920008783571819.
The sulfotransferase (SULTs) catalyzes the sulfonation of a multitude of xenobiotics, hormones and neurotransmitters. This review has summarised the SULT family in detail, the structure of the twelve known enzymes, in their four known groups (SULT1, SULT2, SULT4, and SULT6) and the substrates for each respective SULT. Hepatic sulfonation is a common phase II metabolic mechanism for increasing molecular hydrophilicity in preparation for biliary excretion or efflux across the hepatic basolateral membrane for subsequent renal clearance. To date, a total of 13 human cytosolic SULT genes have been identified which spread across four families; SULT1, SULT2, SULT4, and SULT6. The established structures of SULTs provide evidence for both enzyme/substrate and enzyme/cofactor binary complexes, consistent with a random bi-bi mechanism and ruling out an ordered mechanism in which binding of substrate requires binding of cofactor (or vice versa). Members of the SULT1 family have demonstrated the ability to sulfonate simple (small planar) phenols including estradiol, thyroid hormones, environmental xenobiotics and drugs. The SULT2 family members catalyze sulfonation of hydroxyl groups of steroids, such as androsterone, allopregnanolone, and dehydroepiandrosterone. As yet, no known substrate or function has been identified for the SULT4 family, and the SULT6B1 gene, expressed in the testis of primates, has neither the protein nor its enzymatic activity characterized. The extent of nucleotide variation found in members of the SULT gene family is similar to that observed for other groups of human genes. Substrate inhibition was observed for most substrates with a trend in maximum velocity (V(max)) of *1>*3>*2. There does appear to be an inter-ethnic/inter-racial difference in the incidence of the various SULT1A1 alleles also. There is mounting evidence to suggest that further research and understanding in the area of phase II metabolism and the SULT enzyme will have a great benefit in a clinical setting. Already research in the field is finding links with cancer and sulfonation-related disease, promising to deliver great advances in clinical practice in the future.
磺基转移酶（SULTs）催化多种外源性物质、激素和神经递质的磺化反应。本综述详细总结了SULT家族、已知的12种酶的结构、它们所属的4个已知类别（SULT1、SULT2、SULT4和SULT6）以及每种SULT各自的底物。肝脏磺化是一种常见的II相代谢机制，用于增加分子亲水性，为胆汁排泄或通过肝基底外侧膜流出以随后经肾清除做准备。迄今为止，总共已鉴定出13个人类胞质SULT基因，它们分布在四个家族中：SULT1、SULT2、SULT4和SULT6。SULTs已确定的结构为酶/底物和酶/辅因子二元复合物提供了证据，这与随机双底物机制一致，并排除了底物结合需要辅因子结合（反之亦然）的有序机制。SULT1家族成员已证明能够磺化简单（小平面）酚类，包括雌二醇、甲状腺激素、环境外源性物质和药物。SULT2家族成员催化类固醇羟基的磺化反应，如雄酮、别孕烯醇酮和脱氢表雄酮。迄今为止，尚未确定SULT4家族的已知底物或功能，并且在灵长类动物睾丸中表达的SULT6B1基因，其蛋白质及其酶活性均未得到表征。在SULT基因家族成员中发现的核苷酸变异程度与在其他人类基因群体中观察到的相似。大多数底物都观察到底物抑制现象，最大反应速度（V(max)）的趋势为*1>*3>*2。在各种SULT1A1等位基因的发生率上似乎也存在种族间差异。越来越多的证据表明，在II相代谢和SULT酶领域的进一步研究和理解将在临床环境中带来巨大益处。该领域的研究已经发现了与癌症和磺化相关疾病的联系，有望在未来的临床实践中取得重大进展。
