標題: Mechanism of sulfotransferase pharrnacogenetics in altered xenobiotic metabolism
作者: Chen, Bo-Han
Wang, Chen-Chu
Hou, You-Hua
Mao, Yi-Chih
Yang, Yuh-Shyong
生物科技學系
Department of Biological Science and Technology
關鍵字: single-nucleotide polymorphism;substrate selectivity;sulfotransferase;xenobiotic metabolism
公開日期: 1-Jul-2015
摘要: Introduction: Cytosolic sulfotransferases (SULTs), one of the vital enzymes of detoxication, catalyze the sulfation of native and exogenous hydrophobic molecules. Xenobiotic accumulation can induce a variety of diseases, including cancers. Sulfation facilitates the solubilization and removal of xenobiotics. However, sulfation may activate the pharmacological-activities of xenobiotics. Areas covered: The purpose of this review was to correlate the sequence, structure and function of SULTs. We focused on understanding the sulfation mechanisms of SULT through its sequence variation. We selectively reviewed SULT drug substrates, explained the enzyme-catalyzed sulfation reaction and its kinetic mechanisms, and the effect of amino acid sequence variation, such as single-nucleotide polymorphism, on the enzyme function. Expert opinion: A wealth of information is available in the literature for understanding the detailed mechanisms underlying xenobiotic sulfation. We reviewed information regarding the sequence, structure and reaction mechanism of SULTs and explained how SULT activities altered. In addition to revealing the SULT kinetics, the mRNA expression of specific SULTs in tissues that revealed their distribution in tissues also affects overall SULT activities. Understanding of the structure-function relationship and the reaction mechanism of SULTs is valuable for understanding, preventing and treating diseases.
URI: http://dx.doi.org/10.1517/17425255.2015.1045486
http://hdl.handle.net/11536/127866
ISSN: 1742-5255
DOI: 10.1517/17425255.2015.1045486
期刊: EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
Volume: 11
起始頁: 1053
結束頁: 1071
Appears in Collections:Articles