Sulfonation of curcuminoids: Characterization and contribution of individual SULT enzymes
Sulfonation of curcuminoids: Characterization and contribution of individual SULT enzymes
复制标题
类姜黄素的磺化：各个 SULT 酶的表征和贡献。
DOI：
10.1002/mnfr.201400493
复制
发表时间：
2015-04-01
影响因子：
5.2
通讯作者：
Meng, Shengnan
中科院分区：
文献类型：
--
作者：
Lu, Xiaoyue;Jiang, Kunyu;Meng, Shengnan
作用域
姜黄素口服生物利用度低限制了其在体内的广泛应用，其中一个主要原因是其在体内的快速代谢。磺基转移酶的磺化反应是这类化合物的重要代谢途径。本研究的目的是测定特定代谢指纹图谱、组织特异性速率和反应动力学曲线，以描述姜黄素磺化反应的特征和贡献。
方法和结果
用9种表达的姜黄素异构体和4种混合的人体组织S9组分研究了姜黄素的磺化反应。结果表明，人体小肠是导致姜黄素磺化的主要组织。SULT1A3是催化姜黄素和去甲氧基姜黄素磺化反应的主要异构体，但不催化双脱甲氧基姜黄素磺化反应。SULT1B1只负责姜黄素的磺化反应。虽然SULT1C4和1E1对这三种化合物的硫酸盐结合都有很高的催化作用，但与人小肠S9组分的相关性要弱得多(R(2)=0.100-0.482)。几乎所有姜黄素亚型的动力学曲线都表现为底物抑制动力学。
结论
本研究有助于从分子水平和不同器官水平阐明姜黄素类化合物的代谢和解毒机制。
SCOPE
Poor oral bioavailability of curcuminoids limited their various applications, and one of the main reasons is their rapid metabolism in vivo. Sulfonation via sulfotransferases (SULTs) is an important metabolic pathway for such compounds. The objective of this study is to determine the SULT-isoform-specific metabolic fingerprint, tissue-specific rate, and reaction kinetic profiles to describe the characterization and contribution of curcuminoids sulfonation.
METHODS AND RESULTS
Sulfonation of curcuminoids was investigated by using nine expressed SULT isoforms and four pooled human tissue S9 fractions. The results showed that human small intestine is the predominant tissue responsible for sulfonation of curcuminoids. SULT1A3 is a major isoform catalyzing sulfonation of curcumin and demethoxycurcumin, but not for bisdemethoxycurcumin. SULT1B1 is only responsible for sulfonation of curcumin. Although SULT1C4 and 1E1 could highly catalyze the sulfate conjugations toward all the three compounds, the correlativities with human small intestine S9 fractions were much weaker (R(2) = 0.100-0.482). Almost all the kinetic profiles of the SULT isoforms for curcuminoids exhibited substrate inhibition kinetics.
CONCLUSION
This investigation contributed to elucidate the SULT-mediated metabolism and detoxication of curcuminoids at molecular levels and in different organs.