BIOSYNTHESIS AND CHEMICAL SYNTHESIS OF BILE ACIDS AND THEIR BIOMEDICAL APPLICATIONS

Tanja Šarenac* and Momir Mikov

ABSTRACT

Bile acids are amphiphilic molecules consisting of a hydrophobic and a rigid steroid nucleus, which they are attached a hydrophilic hydroxyl groups and a flexible acidic aliphatic side chain. The steroidal core of bile acids constitutes a saturated cyclopentanoperhydrophenanthrene skeleton, consisting of three six-membered (A, B and C) and one five-membered ring (D). The primary bile acids include cholic and chenodeoxycholic acid. They arise as result of chemical transformation of cholesterol by the effect of various enzymatic reactions in hepatocytes of the liver. Secondary bile acids, which include deoxycholic and lithocholic acid, are formed by the reactions of 7−dehydroxylation and deconjugation of cholic and chenodeoxycholic acid. The aim of this paper is the discussion of biosynthesis and various chemical synthesis of bile acids, as well as the explanation of their biomedical applications. Bile acids, as signaling molecules are involved in the regulation of glucose and lipid metabolism, thermogenesis, inflammatory and immunomodulatory processes, antibacterial protection of the intestinal tract. The most of their effects, bile acids are mediated through nuclear receptor, such as FXR receptors and membrane TGR5 receptors. There are a various possibility for the development of semi−synthetic derivatives of bile acids and synthetic compounds of the nonsteroidal structure, which will have a greater affinity for these receptors, better selectivity and improved pharmacokinetic properties. These therapeutic agents would offer new pharmacotherapeutic possibilities in various metabolic disorders, but also in malignant diseases.

Keywords: Biosynthesis of Bile Acids, Chemical Synthesis, Biomedical Applications of Bile Acids.