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

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...

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Autores principales: Šarenac, Tanja M., Mikov, Momir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168039/
https://www.ncbi.nlm.nih.gov/pubmed/30319399
http://dx.doi.org/10.3389/fphar.2018.00939
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author Šarenac, Tanja M.
Mikov, Momir
author_facet Šarenac, Tanja M.
Mikov, Momir
author_sort Šarenac, Tanja M.
collection PubMed
description 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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spelling pubmed-61680392018-10-12 Bile Acid Synthesis: From Nature to the Chemical Modification and Synthesis and Their Applications as Drugs and Nutrients Šarenac, Tanja M. Mikov, Momir Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2018-09-25 /pmc/articles/PMC6168039/ /pubmed/30319399 http://dx.doi.org/10.3389/fphar.2018.00939 Text en Copyright © 2018 Šarenac and Mikov. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Šarenac, Tanja M.
Mikov, Momir
Bile Acid Synthesis: From Nature to the Chemical Modification and Synthesis and Their Applications as Drugs and Nutrients
title Bile Acid Synthesis: From Nature to the Chemical Modification and Synthesis and Their Applications as Drugs and Nutrients
title_full Bile Acid Synthesis: From Nature to the Chemical Modification and Synthesis and Their Applications as Drugs and Nutrients
title_fullStr Bile Acid Synthesis: From Nature to the Chemical Modification and Synthesis and Their Applications as Drugs and Nutrients
title_full_unstemmed Bile Acid Synthesis: From Nature to the Chemical Modification and Synthesis and Their Applications as Drugs and Nutrients
title_short Bile Acid Synthesis: From Nature to the Chemical Modification and Synthesis and Their Applications as Drugs and Nutrients
title_sort bile acid synthesis: from nature to the chemical modification and synthesis and their applications as drugs and nutrients
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168039/
https://www.ncbi.nlm.nih.gov/pubmed/30319399
http://dx.doi.org/10.3389/fphar.2018.00939
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