Bile acids are detergent substances, that is, capable of dispersing water insoluble lipids in aqueous solution. For this reason bile acids play a leading role in the processes of digestion and absorption of lipids.
Bile acids are produced by the liver from cholesterol and - together with their conjugates and their salts - are the main constituents of bile.
Primary bile acids (produced by the liver)
The 7-α-hydroxylase enzyme starts the series of biochemical transformations that, starting from cholesterol, lead to the synthesis of primary bile acids: cholic acid and chenodeoxycholic acid (or simply chenico).
7-α-hydroxylase represents the limiting enzyme in bile acid synthesis.
Conjugated bile acids
In bile, cholic and chenodeoxycholic acids are mostly conjugated with two amino acids, glycine and taurine (with a ratio of about 3: 1), and as such they are called glycocolic, taurocolic (more abundant), glycochene-dioxycholic acids and taurochenodeoxicolici . This conjugation increases the water solubility of bile acids.
Bile salts
Since bile is an alkaline liquid rich in sodium and potassium, it is believed that primary bile acids and their conjugates are largely present in the form of salts (mainly sodium).
Bile functions
In the interdigestive phase, bile - synthesized by the liver - is concentrated in the gall bladder. Once poured into the intestine as needed, thanks to the primary bile salts and other amphipathic substances (phospholipids and lecithins), bile facilitates the digestion and absorption of fats and fat-soluble vitamins. With its alkalinity, bile neutralizes the frankly acidic pH of gastric secretions (HCl); it also stimulates intestinal peristalsis and exerts an antiseptic action against the bacterial flora, inhibiting putrefactive phenomena. The products deriving from the degradation of hemoglobin (bilirubin), substances with toxic or pharmacological action and others of an endogenous nature (thyroid hormones, estrogens, etc.) are also removed from the body through bile.
Secondary bile acids (produced by intestinal bacterial flora)
At the intestinal level the bile acids are partly deconjugated and dehydroxylated by the enzyme 7-α-dehydroxylase produced by the bacterial flora of the intestine. The products of these reactions are called secondary bile acids and are mainly represented by desoxycholic acid and lithocolic acid, respectively derived from cholic acid and chenodeoxycholic acid.
In total, the majority (94-98%) of bile acids present in the intestine are reabsorbed and returned to the liver via the portal circle. In the small intestine and in the colon there is a passive reabsorption which becomes active only in the terminal ileum (conclusive portion of the small intestine). Only a small part of the bile acids is eliminated with the faeces; this quota is mainly represented by lithocolic acid, which is scarcely reabsorbed.
The bile acids, once reabsorbed, reach the hepatic level where they are recycled and secreted again into the bile (enterohepatic circulation of bile acids). Furthermore, their concentration influences the ex-novo synthesis of bile acids, which is the more stimulated the lower the proportion of recyclable bile acids (the secondary ones reabsorbed in the intestine), and vice versa.
Resins sequestering bile acids (see cholestyramine)
As mentioned in the previous paragraph, a drug capable of limiting the intestinal reabsorption of bile acids stimulates the synthesis from scratch of the same. Since this process uses cholesterol present in the body, these drugs lower cholesterolemia.
Bile acids in the blood, high bile acids
The bile salts escaped from liver uptake determine the concentrations present in the blood; for this reason hepatocellular damage prematurely reduces the hepatic uptake of bile acids (in particular from the blood coming from the intestine). High blood levels of bile acids, and in particular secondary ones, are therefore recorded in the presence of hepatitis A, hepatitis B, infectious mononucleosis, cirrhosis, liver tumors and drug or alcohol liver diseases.
The levels of bile acids in the blood, and in particular the primary ones, typically increase in cholestasis, such as when - for example - a calculation prevents the outflow of bile into the intestine. The same condition occurs in some women during pregnancy, due to the characteristic hormonal changes that accompany it.
