Zhou J, Zhang J, Xie W
Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, 656 Salk Hall, Pittsburgh, PA 15261, USA.
Curr Drug Metab. 2005 Aug;6(4):289-98. doi: 10.2174/1389200054633853.
UDP-glucuronosyltransferases (UGTs) belong to the Phase II drug metabolizing enzymes. UGTs mediate the transfer of glucuronic acid, from UDP glucuronic acid to predominantly hydrophobic xeno- and endobiotic chemicals, thus facilitating their detoxification and excretion. Deficiency in the expression and/or activity of UGTs may lead to genetic and acquired diseases such as Crigler-Najjar syndrome and jaundice. UGT genes are classified into UGT1A and UGT2B subfamily, and each subfamily and each isoform shows tissue-specific distribution pattern. The underlying mechanisms for this tissue specificity are not fully understood. Emerging evidence have demonstrated that nuclear receptors (NR), such as pregnane X receptor (PXR), constitutive androstane receptor (CAR), peroxisome proliferator-activated receptor (PPAR), can regulate UGTs and this NR-mediated regulation may contribute to the tissue-specific expression pattern of UGTs. The regulations are believed to be both receptor- and UGT isoform-specific. In addition, UGTs are also subject to the regulation by aryl hydrocarbon receptor (AhR) and other tissue-specific transcription factors. Based on their capacity to catalyze the glucuronidation of xenobiotics and endobiotics, UGTs play an important role in hormonal homeostasis, energy metabolism, bilirubin clearance, and xenobiotic detoxification. Therefore, elucidating UGT regulation by nuclear receptors has broader significance in understanding UGT's function in various physiological and patho-physiological conditions.
尿苷二磷酸葡萄糖醛酸转移酶（UGTs）属于Ⅱ相药物代谢酶。UGTs介导葡萄糖醛酸从尿苷二磷酸葡萄糖醛酸转移至主要为疏水性的外源性和内源性化学物质，从而促进它们的解毒和排泄。UGTs表达和/或活性的缺乏可能导致诸如克里格勒-纳贾尔综合征和黄疸等遗传性和获得性疾病。UGT基因分为UGT1A和UGT2B亚家族，每个亚家族和每个同工型都表现出组织特异性分布模式。这种组织特异性的潜在机制尚未完全了解。新出现的证据表明，核受体（NRs），如孕烷X受体（PXR）、组成型雄烷受体（CAR）、过氧化物酶体增殖物激活受体（PPAR），可以调节UGTs，这种NR介导的调节可能有助于UGTs的组织特异性表达模式。据信这些调节是受体和UGT同工型特异性的。此外，UGTs也受到芳烃受体（AhR）和其他组织特异性转录因子的调节。基于它们催化外源性和内源性物质葡萄糖醛酸化的能力，UGTs在激素稳态、能量代谢、胆红素清除和外源性物质解毒中发挥重要作用。因此，阐明核受体对UGTs的调节在理解UGTs在各种生理和病理生理条件下的功能方面具有更广泛的意义。
