Biosynthesis and biotransformation of bile acids

Sarenac, M Tanja; Mikov, Momir

doi:10.5937/hpimj1701469s

Cited by 3 publications

(6 citation statements)

References 18 publications

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“…Some other enzymes are also involved in this pathway, consisting of a cascade of 14 steps (Chiang, 2004). In physiological conditions, the classic pathway may be the main pathway, constituting about 90% and 75% in human and mice, respectively, in the total contribution (Šarenac and Mikov, 2017).…”

Section: The Classic Ba Biosynthetic Pathwaymentioning

confidence: 99%

“…UDCA, 3α,7β-dihydroxy-5β-cholanic acid), is an acidic steroid that is synthesized from cholesterol in hepatocytes (Wang and Wu, 2017). Among all the BAs, only UDCA was approved by the US Food and Drug Administration (FDA) for the treatment of PBC (Šarenac and Mikov, 2017). UDCA is widely utilized in the treatment of various diseases related to liver injury.…”

Section: Introductionmentioning

confidence: 99%

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Ursodeoxycholic acid: a systematic review on the chemical and biochemical properties, biosynthesis, sources and pharmacological activities

Raunsai

Elfahmi

Chahyadi

et al. 2021

CRBB

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Background: Background: Ursodeoxycholic acid (UDCA), a secondary bile acid, is an acidic steroid synthesized from cholesterol in hepatocytes. UDCA is widely used for the treatment of various diseases related to liver injury. The use of UDCA to treat non-liver diseases has also been developed recently, such as neurodegenerative diseases, cancer, and obesity. Due to the important role of UDCA on human health, numerous studies in understanding its chemical and pharmacological properties have been published. Methods: Literature sources were obtained from online databases such as Science Direct, Google Scholar, Scopus and PubMed using keywords relating to the purpose of study. Critical analysis and review were performed for all literatures. Results: UDCA is a steroid compound with pharmacological properties. Seventeen enzymes are involved in its biosynthesis, which has been proposed in four pathways: classic, alternative, the Yamazaki, and 25-hydroxylation pathways. UDCA can be isolated from bovine bile, bear bile or all Ursidae, human, rabbit, cow, rat, hamster, sheep, pig, and plant. UDCA has been used in the treatment of several diseases such as primary biliary cirrhosis, intrahepatic cholestasis of pregnancy, hepatolithiasis associated with Caroli syndrome gallstones, cystic fibrosis, hepatitis C virus, chronic heart failure, neurodegenerative diseases, and obesity, as well as in the prevention of cancer. Conclusion: UDCA has a wide range of the pharmacological properties. Further investigations on its efficacy and safety on humans are required before it could be used for several indications. All genes which are responsible for UDCA biosynthesis have been elucidated. That said, further genetic engineering studies in order to find other prospective sources of UDCA could be a challenge for the future research.

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Section: The Classic Ba Biosynthetic Pathwaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ursodeoxycholic acid: a systematic review on the chemical and biochemical properties, biosynthesis, sources and pharmacological activities

Raunsai

Elfahmi

Chahyadi

et al. 2021

CRBB

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“…lithocholic acid (LCA). Other changes in the structure of BAs include oxidation of hydroxyl groups into oxo groups, epimerization of C 3 , C 7 or C 12 hydroxyl groups and isomerization of the compound between rings A / B (Sarenac and Mikov, 2017 ). It results in the epimerization of the 7α-hydroxyl group of CDCA to the 7β-epimer of UDCA with properties favorable to both the host organ and the intestinal bacteria (Mikov et al, 2007 ) (Scheme 1 ).…”

Section: Intestinal Phase Of Biotransformation Of Basmentioning

confidence: 99%

“…Alternatively, less than 10% of the total amount of BAs is synthesized. The alternative pathway is thought to be significantly more active in childhood, while later on in the course of life, the classical pathway becomes significant in the contribution to the composition of bile acid pool (Scheme 1 ; Sarenac and Mikov, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

“…This process is catalyzed by the enzyme (BACS) and bile acid–CoA: amino acid N acetyl transferase. The amide link increases the ionization constant of BAs (pKa~ 5), so that the conjugates of glycine have a pKa value of about 3 (at concentrations below CMC), while the presence of the sulphuric group of taurine provides pKa < 2(Sarenac and Mikov, 2017 ). By the conjugation process, there is a possibility of reducing the precipitation of bile salts, as well as increasing hydrophilicity of molecules with consequently reduced potential for passing through the cell membrane and reduced cytotoxic and membranolytic properties (Kevresan et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

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Bile Acid Synthesis: From Nature to the Chemical Modification and Synthesis and Their Applications as Drugs and Nutrients

2018

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Bile acids (BAs) are amphiphilic molecules with 24 carbon atoms and consist of a hydrophobic and a rigid steroid nucleus, to which are attached a hydrophilic hydroxyl group and a flexible acidic aliphatic side chain. The steroidal core of BAs constitutes a saturated cyclopentanoperhydrophenanthrene skeleton, consisting of three six-membered (A, B, and C) and one five-membered ring (D). Primary BAs are produced in the hepatocytes, while secondary BAs are formed by modifying the primary BAs in the intestinal lumen, i.e., by the reactions of 7α-dehydroxylation and deconjugation of cholic acid (CA) and chenodeoxycholic acid (CDCA). The most important secondary BAs are deoxycholic acid (DCA) and lithocholic acid (LCA). The BAs realize their effects through nuclear farnesoid X receptors (FXRs) and membrane TGR5 receptors. It has been found that BAs are also associated with other receptors such as the vitamin D receptor (VDR), from which the most significant ligand is calcitriol, as well as with pregnane X receptor (PXR) and potentially with the constitutive androstane receptor (CAR), whose ligands are numerous, structurally different xenobiotics that show greater affinity to BAs. The BAs as therapeutic agents (drugs) have the potential to produce beneficial effects in cases of sexually transmitted diseases, primary biliary cirrhosis (PBC), primary sclerosing cholangitis, gallstones, digestive tract diseases, cystic fibrosis, and cancer. Ursodeoxycholic acid (UDCA) was the only drug approved by the US Food and Drug Administration (FDA) for the treatment of PBC. In this paper, the different pathways of bile acid biosynthesis are explained as well as chemical modifications and the synthesis of different keto derivatives of BAs. Also, the effects of BAs on digestion of nutrients, their role as drugs, and, in particular, the emphasis on the hypoglycemic properties of 7α, 12α-dihydroxy−12–keto−5β-cholanic acid in the treatment of diabetes mellitus are examined in detail.

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Bile Acids and Microbiota Interplay in Pancreatic Cancer

Malhotra

Palanisamy

Caparrós-Martín

et al. 2023

Cancers

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Evidence suggests the involvement of the microbiota, including oral, intra-tumoral and gut, in pancreatic cancer progression and response to therapy. The gut microbiota modulates the bile acid pool and is associated with maintaining host physiology. Studies have shown that the bile acid/gut microbiota axis is dysregulated in pancreatic cancer. Bile acid receptor expression and bile acid levels are dysregulated in pancreatic cancer as well. Studies have also shown that bile acids can cause pancreatic cell injury and facilitate cancer cell proliferation. The microbiota and its metabolites, including bile acids, are also altered in other conditions considered risk factors for pancreatic cancer development and can alter responses to chemotherapeutic treatments, thus affecting patient outcomes. Altogether, these findings suggest that the gut microbial and/or bile acid profiles could also serve as biomarkers for pancreatic cancer detection. This review will discuss the current knowledge on the interaction between gut microbiota interaction and bile acid metabolism in pancreatic cancer.

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Biosynthesis and biotransformation of bile acids

Cited by 3 publications

References 18 publications

Ursodeoxycholic acid: a systematic review on the chemical and biochemical properties, biosynthesis, sources and pharmacological activities

Ursodeoxycholic acid: a systematic review on the chemical and biochemical properties, biosynthesis, sources and pharmacological activities

Bile Acid Synthesis: From Nature to the Chemical Modification and Synthesis and Their Applications as Drugs and Nutrients

Bile Acids and Microbiota Interplay in Pancreatic Cancer

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