title: Mechanism of sulfotransferase pharmacogenetics in altered xenobiotic metabolism.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Chiao Tung University, Department of Biological Science and Technology , 75 Po-Ai Street, Hsinchu , Taiwan +886 3 573 1983 ; +886 3 572 9288 ; ysyang@mail.nctu.edu.tw.
authors.forename: Bo-Han
authors.initials: BH
authors.lastname: Chen
authors.forename: Chen-Chu
authors.initials: CC
authors.lastname: Wang
authors.forename: You-Hua
authors.initials: YH
authors.lastname: Hou
authors.forename: Yi-Chih
authors.initials: YC
authors.lastname: Mao
authors.forename: Yuh-Shyong
authors.initials: YS
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D015262:Xenobiotics / Q000009:adverse effects / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D015262:Xenobiotics; D015238:Sulfotransferases
keywords: single-nucleotide polymorphism; substrate selectivity; sulfotransferase; xenobiotic metabolism