JLR Commentaries
Hepatic thyroid hormone receptor β1 agonism: good for lipids, good for bile?
Hepatic bile formation plays an essential role in lipid digestion and absorption, cholesterol homeostasis, and excretion of lipid soluble metabolites and xenobiotics. Bile is a complex, lipid-rich micellar solution composed primarily of water, inorganic solutes, and organic solutes such as amphipathic conjugated bile acids (BAs), the membrane phospholipid phosphatidylcholine (PC), cholesterol, bile pigments, and endogenous metabolites (1). The major organic solutes, BAs, phospholipids, and cholesterol are termed “biliary lipids” and their secretion into bile is mediated by three distinct canalicular membrane ABC transporters, ABCB11(BSEP), ABCB4 (MDR3) (Abcb4/Mdr2 in rodents), and ABCG5/ABCG8, respectively (1).Will the real bile acid sulfotransferase please stand up? Identification of Sult2a8 as a major hepatic bile acid sulfonating enzyme in mice
This year marks the 50th anniversary of the publication by Robert Palmer (1, 2) recognizing the formation of bile acid sulfates as a mechanism for bile acid elimination in humans. Like steroids, bile acids undergo sulfonation in liver and other tissues [reviewed by Alnouti in (3)]. This important phase II detoxification reaction transfers a sulfonate group (SO3−) from the universal donor, 3′-phosphoadenosine 5′-phosphosulfate (PAPS), to a hydroxyl, amine, or carboxylic acid group of a substrate.
