Bile acids: Chemistry, physiology, and pathophysiology

Abstract

The family of bile acids includes a group of molecular species of acidic steroids with very peculiar physical-chemical and biological characteristics. They are synthesized by the liver from cholesterol through several complementary pathways that are controlled by mechanisms involving fine-tuning by the levels of certain bile acid species. Although their best-known role is their participation in the digestion and absorption of fat, they also play an important role in several other physiological processes. Thus, genetic abnormalities accounting for alterations in their synthesis, biotransformation and/or transport may result in severe alterations, even leading to lethal situations for which the sole therapeutic option may be liver transplantation. Moreover, the increased levels of bile acids reached during cholestatic liver diseases are known to induce oxidative stress and apoptosis, resulting in damage to the liver parenchyma and, eventually, extrahepatic tissues. When this occurs during pregnancy, the outcome of gestation may be challenged. In contrast, the physical-chemical and biological properties of these compounds have been used as the bases for the development of drugs and as pharmaceutical tools for the delivery of active agents.

Organic anion transporting polypeptide 1a/1b–knockout mice provide insights into hepatic handling of bilirubin, bile acids, and drugs

“…Bile acids play an important role in several physiological processes and they are therefore subject to strict homeostasis (34). Bile acids are synthesized from cholesterol in the liver and undergo extensive enterohepatic circulation, a process in which Na + taurocholate cotransporting polypeptide (NTCP), bile acid export pump (BSEP/ABCB11), apical sodium bile acid transporter (ASBT), and organic solute transporter (OST α /OST β ) play important roles (reviewed in refs.…”

Bile acid regulates MUC2 transcription in colon cancer cells via positive EGFR/PKC/Ras/ERK/CREB, PI3K/Akt/IκB/NF-κB and p38/MSK1/CREB pathways and negative JNK/c-Jun/AP-1 pathway

“…Secondary bile acids, such as DCA, which have been implicated in tissue injury and colorectal carcinogenesis have also been reported to cause altered expression of mucins such as MUC2, a major goblet cell mucin, in colon cancer cells (15,16). Bile acids have been reported to have diverse effects on the cells in the liver and gastrointestinal tract, such as oxidative stress, apoptosis and cell proliferation mediated by various cell signaling pathways (8,27).…”

“…Bile acids are amphiphilic molecules that promote the processing of dietary fat absorption (8). Primary bile acids such as cholic acid and chenodeoxycholic acid are synthesized and conjugated by amino acids in the liver and are secreted in the bile into the intestinal lumen where they are hydrolyzed to secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid by the action of bacterial enzymes in the colon (8).…”

“…Primary bile acids such as cholic acid and chenodeoxycholic acid are synthesized and conjugated by amino acids in the liver and are secreted in the bile into the intestinal lumen where they are hydrolyzed to secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid by the action of bacterial enzymes in the colon (8). The secondary bile acids have been reported to be more toxic to colonic epithelial cells than the primary bile acids and also have been reported to be a tumor promoter in the animal models (9,10).…”

The association between HSD3B7 gene variant and Parkinson's disease in ethnic Chinese

“…When combining the finding from a pathway‐based association study, there is a potential contribution of rs9938550 to HSD3B7 on PD (Song & Lee, 2013). In the classical pathway, HSD3B7 catalyzes the second step of bile acid formation (Monte, Marin, Antelo, & Vazquez‐Tato, 2009), and its mutations may reduce the synthetic capability (Cheng et al., 2003). Interestingly, when the main product, chenodeoxycholic acid (CDCA), converts into a β‐configuration ursodeoxycholic acid (UDCA) and its taurine‐conjugated form (TUDCA), the anti‐apoptotic effect is demonstrated (Ackerman & Gerhard, 2016; Amaral, Viana, Ramalho, Steer, & Rodrigues, 2009; Hirano, Masuda, & Oda, 1981).…”