Bile acids are a group of biochemical substances that belong to the large family of steroids, molecules that have acquired a bad reputation over the last century due to their association with cardiovascular diseases, sports doping or uncontrolled intake of hormones or corticosteroid-type drugs.

However, steroids, with cholesterol as the main component, are absolutely essential for the proper functioning of cells, as their functions as a chemical substance are many and varied: regulatory, structural, mediating, emulsifying, precursors of other important molecules, etc.

As fine chemical suppliers, in this article we will briefly introduce their characteristics and properties, as this is a broad field of study and further in-depth study requires the consultation of a specialised bibliography.

Structure of bile acids

As mentioned above, bile acids are steroids and, therefore, their molecule contains the 4-fused ring system of the cyclopentane-perhydrophenanthrene (also called “gonane” or “sterane”).

The carbon skeleton of sterane, the simplest steroid in existence. The numbering of the carbon skeleton is shown, following IUPAC recommendations.

The A and B rings are usually fused in cis-configuration, although the A ring can opt for a chair (more stable) or ship (less stable) conformation. On the other hand, the remaining rings, B/C and C/D, are fused in a trans configuration.

Structure of 5a-cholanic acid (left) and 5b-cholanic acid (right), showing the effect of the A/B cis and A/B trans conformations on the structure.

In terms of functionality, as fine chemical suppliers we can state that the hydroxyl group is common and can be found in the A, B and C rings, and in particular, it is usually present in the C3, C6, C7, C12  and C23 positions. It is also common to find methyl groups in the C10 and C13 positions.

The stereochemistry of steroids is very important. Based on the methyl chemical at C19, the hydrogens at C5 and C8 have cis-isomerism, while those at C9 and C14 have trans-isomerism.

Cholesterol structure with carbon skeleton numbering.

Finally, as fine chemical suppliers, it is common to find an aliphatic chain at the C17 position with varying degrees of functionality. The length and functionality of this chain, the presence of methyl and hydroxyl groups and the stereochemistry of the molecule are the main characteristics of this chemical that differentiate a particular steroid from others.

Biosynthesis and classification

In nature, the basic bile acid is cholanic acid, from which the various bile acids are obtained by the hydroxylation of various positions of the carbon skeleton. However, this acid is hardly found in mammals.

In fact, the main source of bile acids is cholesterol, a highly hydrophobic molecule despite its alcohol function, which is a major constituent of cell membranes. However, when the end of the aliphatic chain is oxidised, we obtain a bile acid, and this is the function performed by liver cells, providing what are known as the primary bile acids: cholic acid and chenodeoxycholic acid:

These acids pass into the digestive tract via the bile bladder, specifically into the duodenum, where there is a relatively acidic pH (5-6.5). However, the pKa of these acids is lower, between 3 and 5. As fine chemical suppliers, we know that this is a problem because under these conditions the acids will be mostly protonated, making them very poorly soluble in aqueous media. That is why, before being released into the intestine, the liver conjugates these acids with glycine or taurine, so that an ionic pair is formed which makes them soluble in aqueous media.

Later, the intestinal flora comes into play by breaking down this ionic pair and transforming these acids into new ones, the secondary bile acids, mainly by dehydroxylation of the C7 position. The intestinal flora can go further and undergo other transformations such as epimerisation or conjugation with N-acetylglucosamine, resulting in tertiary bile acids.

Finally, these acids can be recovered from the gut and returned to the liver to be reused again. This is known as enterohepatic circulation:

Functions of bile acids

Bile acids have surface-active properties when they are in a neutral or basic medium, with the aliphatic end, containing the carboxyl group, as the hydrophilic part, while the rest of the molecule is quite lipophilic. Therefore, its main function is to emulsify fats and non-polar substances into aggregates known as micelles, allowing them to be absorbed by the small intestine and remain soluble in the blood. This facilitates the work of lipases, enzymes that will degrade lipids to free fatty acids and glycerol.

In addition to their emulsifying function, these chemicals also act as chemical mediators, as they bind to various cell receptors in order to trigger important biochemical processes (cell signalling). They are even involved in mechanisms that regulate tissue inflammation.

Thus, among other functions, they are known to be involved in calcium mobilisation, activation of protein C kinase, synthesis of cyclic AMP and secretion of pro-inflammatory cytokines. They are also involved in oxidative processes in the mitochondria and are even involved in insulin receptor signalling. In addition, they regulate cholesterol levels or are involved in the elimination of catabolites such as bilirubin.

In short, bile acids have many functions, and although it may seem paradoxical today, we have seen that the presence of cholesterol is essential for the body to function properly. Provided, of course, that it is present in the right quantities then the problem is reduced to controlling the intake of this steroid. 




  • Kuhajda, K. et al, “Structure and origin of bile acids: an overview”, European Journal of Drug Metabolism and Pharmacokinetics 2006, Vol. 31, No.3, pp. I3S-143
  • Chiang, J.Y.L., “Bile acids: regulation of synthesis”, Journal of Lipid Research, Volume, 50, 2009, 1955-66.
  • Singh, J. et al., “A Review on Bile Acids: Effects of the Gut Microbiome, Interactions with Dietary Fiber, and Alterations in the Bioaccessibility of Bioactive Compounds”, J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.8b07306