Regulation of Sulfotransferase and UDP-Glucuronosyltransferase Gene Expression by the PPARs

Figure 1

Example reactions catalyzed by PPAR-regulated SULT and UGT enzymes. The upper panel shows the SULT2A1- and SULT2B1b-catalyzed 3-sulfonation of the prototype substrates, dehydroepiandrosterone and cholesterol, respectively. Human SULT2A1 is transcriptionally regulated by PPAR𝛼 in human hepatocytes, while SULT2B1b is regulated by PPAR𝛼, PPAR𝛿 and PPAR𝛾 in keratinocytes. The lower panel shows the glucuronidation of bilirubin, 𝑝-nitrophenol and hyodeoxycholic acid, which are prototype substrates for UGT1A1, UGT1A6, and UGT2B4, respectively. UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, and UGT2B4 have all been identified as PPAR target genes. PAPS, 3^′-phosphoadenosine-5^′-phosphosulfate; UDP-GA, uridine-5^′-diphospho-𝛼-D-glucuronic acid.