UDP-glucuronosyltransferases (UGTs) and their related metabolic cross-talk with internal homeostasis: A systematic review of UGT isoforms for precision medicine. (July 2017)

• Record Type: Journal Article
• Authors: Yang, Na; Sun, Runbin; Liao, Xiaoying; Aa, Jiye; Wang, Guangji
• Is Part Of: Pharmacological research. Volume 121(2017:Jul.)
• Page Start: 169
• Page End: 183
• Publication Date: 2017-07
• Subjects: UGT UDP glucuronosyltransferases -- DDIs drug-drug interactions -- DMEs drug metabolizing enzymes -- LC–MS/MS liquid chromatography coupled with tandem mass spectrometry -- UDPGA uridine diphosphate glucuronic acid -- AA arachidonic acid -- HETEs hydroxyeicosatetraenoic acids -- PG prostaglandin -- SNPs single nucleotide polymorphisms -- BaP benzo(a)pyrene -- Nrf2 nuclear factor erythroid 2-related factor 2 -- AhR aryl hydrocarbon receptor -- CAR constitutive androstane receptor -- PXR pregnane X receptor -- PPARα peroxisome proliferator-activated receptor -- AREs antioxidant response elements -- XREs xenobiotic response elements -- TCDD 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin -- TCPOBOP 1, 4-bis[2-(3, 5-dichloropyridyloxy)]benzene -- PCN pregnenolone-16α-carbonitrile -- CLFB clofibrate -- OPZ oltipraz -- SN-38 7-ethyl-10-hydroxycampothecin -- HNF hepatocyte nuclear factor -- NASH nonalcoholic steatohepatitis -- NAFLD nonalcoholic fatty liver disease -- LPS lipopolysaccharide -- TNBS trinitrobenzene sulfonic acid -- ROS reactive oxygen species -- JNK c-Jun N-terminal kinase -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells -- TNFα tumor necrosis factorα -- IL-1β interleukin-1β -- IL-6 interleukin-6 -- PhIP 2-amino-1-methyl-6-phenylimidazo(4, 5-b)pyridine; UDP-glucuronosyltransferases -- Glucuronidation -- Homeostasis -- Diseases risk -- Toxicity -- Precision medicine; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2017.05.001
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: UDP-glucuronosyltransferases (UGTs) are the primary phase II enzymes catalyzing the conjugation of glucuronic acid to the xenobiotics with polar groups for facilitating their clearance. The UGTs belong to a superfamily that consists of diverse isoforms possessing distinct but overlapping metabolic activity. The abnormality or deficiency of UGTs in vivo is highly associated with some diseases, efficacy and toxicity of drugs, and precisely therapeutic personality. Despite the great effects and fruitful results achieved, to date, the expression and functions of individual UGTs have not been well clarified, the inconsistency of UGTs is often observed in human and experimental animals, and the complex regulation factors affecting UGTs have not been systematically summarized. This article gives an overview of updated reports on UGTs involving the various regulatory factors in terms of the genetic, environmental, pathological, and physiological effects on the functioning of individual UGTs, in turn, the dysfunction of UGTs induced disease risk and endo- or xenobiotic metabolism-related toxicity. The complex cross-talk effect of UGTs with internal homeostasis is systematically summarized and discussed in detail, which would be of great importance for personalized precision medicine.