The human body uses cholesterol to synthesize bile acids, which are important for the digestion of fats. The primary bile acid, cholic acid, is very similar in structure to cholesterol. Cholic acid is missing the double bond in the second ring, has two more hydroxyl (OH) groups attached to the steroid ring structure, and has a shortened hydrocarbon tail, the ending of which has been converted to a carboxyl (COOH) group.
Bile Acids Are Emulsifying Agents
Bile acids are amphipathic. This means that they have both water-soluble and water-insoluble (or fat-soluble) parts. Emulsifying agents are amphipathic molecules that are able to mix fats with water. For example, eggs contain an amphipathic substance called lecithin that makes them useful as emulsifying agents in baking.
In order for the human digestive system to digest fats, they must be emulsified into the digestive juices, because the enzymes that break them down are water-soluble.
In bile acids, the hydroxyl (OH) groups are water-soluble, and the methyl (CH3) groups are fat-soluble. The hydroxyl groups all face one direction — for example, toward you from the picture above — while the methyl groups face the opposite direction — for example, away from you from the picture above — making one side of the bile acid water-soluble and the other side fat-soluble.
This characteristic allows bile salts to break up large globs of fat, connecting to the fat on one side, and connecting to the water on the other, thus mixing the fats and water together.
Synthesis and Storage of Bile Acids
Bile acids are synthesized from cholesterol in the liver. First, hydroxyl (OH) groups are inserted at several points, shown in the above picture; second, the second ring of cholesterol loses its double-bond; finally, the hydrocarbon tail is shortened by three carbons, and a carboxyl group is added to the end.
The bile salt shown above is called cholic acid, which contains three hydroxyl groups. The other primary bile acid is called chenodeoxycholic acid, which contains only two hydroxyl groups. These are the "primary" bile acids, although there are other "secondary" bile acids synthesized from primary bile acids by intestinal bacteria as well.
Bile acid synthesis is up-regulated by cholesterol and down-regulated by cholic acid. This means that the higher the cholesterol to cholic acid ratio is, the faster bile acids will be produced. As bile acids are produced, and the concentration of cholesterol lowers and the concentration of cholic acid rises, bile acid synthesis slows down.
Bile Acids are Precursors to Bile Salts
Before bile acids leave the liver, they are converted to bile salts. This involves the replacement of the hydrogen on the end of the carboxyl group with either the amino acid glycine or the amino acid taurine. There are four primary bile salts formed from this reaction:
At the pH (a measure of acidity determined by the concentration of hydrogen ions in a solution) normally present in intestinal digestive juices, the glycine and taurine completely separate from the bile acids within the bile salts. On the other hand, bile acids alone, if not converted to bile salts, will contain a hydrogen ion that tends to stick to the carboxyl group.
Since the carboxyl group is more water-soluble when the hydrogen ion or amino acid is separated from it, bile salts, which have amino acids that completely separate from the carboxyl group, are more water-soluble than bile acids, which have a hydrogen ion that likes to stick to the carboxyl group.
This makes bile salts more effective than bile acids at mixing fats with water. Thus, bile salts are more effective at mixing fats with the water-soluble enzymes that digest them.
Glycine forms of bile salts outnumber taurine forms of bile salts by 3 to 1. After bile salts are produced in the liver, they either flow through the bile duct into the duodenum, which is the first of three sections of the small intestine, to be used immediately for digestion, or they are stored in the gall bladder, where they are saved for future digestive requirements.
Circulation of Bile Salts
Bile salts are produced in the liver, and secreted through the bile duct into the duodenum, the first section of the small intestine. 95% of bile salts are reabsorbed through the ileum, the third and final part of the small intestine, where they travel through the blood, attached to a blood protein called "albumin," back to the liver. This circulation is called enterohepatic circulation.
About 15 to 30 grams of bile salts are circulated through this sequence each day, while about 0.5 grams are lost in the feces and about 0.5 grams are synthesized anew by the liver.
You can peruse the references, share this article, or leave a comment below.
Read more about the author, Chris Masterjohn, PhD, here.
Harvey et al., Biochemistry: 3rd Edition, Baltimore: Lippincott Wiliams and Wilkins, 2005, pp. 222-223.