{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have unveiled a novel PPARα‐dependent bile acid sulfotransferase in mouse liver, originally designated mL‐STL, which is upregulated during fasting. This enzyme exhibits narrow sulfonating activity specifically toward 7α‐hydroxylated primary bile acids (e.g., cholic acid, chenodeoxycholic acid, and α‐muricholic acid), suggesting that it plays a central role in detoxifying bile acids during periods of energy deprivation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n \nStructural and mechanistic investigations of mouse bile acid sulfotransferases have further refined our understanding of 7α‐OH–specific sulfonation. Detailed mutational analyses and crystallographic studies of SULT2A8 have identified unique catalytic residues, such as His48 (and Leu99 in one study), as well as Lys44 and Glu237, that are critical for positioning the bile acid substrate in a configuration distinct from the human 3α‐OH–sulfating enzyme. These findings elucidate a unique substrate‐binding mode in mouse SULT2A8 that underpins the species‐specific sulfation at the 7α position."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": "\n \nPhysiologically, SULT2A8 has been demonstrated to be a male‐predominant, liver‐specific enzyme essential for maintaining bile acid and cholesterol homeostasis during energy deprivation. In vivo studies using Sult2a8‐haplodeficient mice revealed a significant drop in 7α‐OH sulfonating activity under fasting conditions, which corresponded with altered bile acid profiles and decreased plasma cholesterol levels, highlighting its therapeutic potential for modulating metabolic diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lu Feng, Yee-Lok Yuen, Jian Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of a novel PPARα-regulated and 7α-hydroxyl bile acid-preferring cytosolic sulfotransferase mL-STL (Sult2a8)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M074302"}], "href": "https://doi.org/10.1194/jlr.M074302"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28442498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28442498"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Takehiko Shimohira, Katsuhisa Kurogi, Ming-Cheh Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The critical role of His48 in mouse cytosolic sulfotransferase SULT2A8 for the 7α-hydroxyl sulfation of bile acids."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Biotechnol Biochem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/09168451.2018.1464897"}], "href": "https://doi.org/10.1080/09168451.2018.1464897"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29685090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29685090"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kai Wang, Yan-Chun Chan, Pui-Kin So, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of mouse cytosolic sulfotransferase SULT2A8 provides insight into sulfonation of 7α-hydroxyl bile acids."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jlr.2021.100074"}], "href": "https://doi.org/10.1016/j.jlr.2021.100074"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33872606"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33872606"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Takamasa Teramoto, Takeaki Nishio, Katsuhisa Kurogi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The crystal structure of mouse SULT2A8 reveals the mechanism of 7α-hydroxyl, bile acid sulfation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2021.04.113"}], "href": "https://doi.org/10.1016/j.bbrc.2021.04.113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34030040"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34030040"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kai Wang, Martin Yan-Chun Chan, Jian Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Male-biased fasting-induced changes in hepatic tauro-cholic acid and plasma cholesterol in Sult2a8-haplodeficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transgenic Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11248-020-00215-w"}], "href": "https://doi.org/10.1007/s11248-020-00215-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33029720"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33029720"}]}]}]}