In this article we will discuss about:- 1. Variety and Chemistry of Bile Salts 2. Synthesis of Bile Salts 3. Enterohepatic Circulation and Fate 4. Functions.
Variety and Chemistry of Bile Salts:
In the human bile there are two bile salts almost in equal proportion.
1. Sodium taurocholate.
2. Sodium glycocholate.
These are the sodium salts of taurocholic and glycocholic acids respectively.
Four bile acids, cholic acid (C23H39O3.COOH), desoxycholic acid, chenodesoxycholic acid, and lithocholic acid are present in human bile. They are formed from cholesterol, the site of synthesis being liver mitochondrial system. They are also present in the bile in free form. Cholic acid forms soluble compounds with many insoluble substances such as fatty acids, higher alcohols, etc. Upon this property depends the hydrotropic action of bile salts?
Synthesis of Bile Salts:
Site for Synthesis:
Evidence accumulated so far, indicates that liver is the site for the synthesis of bile salts. When bile duct is tied, the bile salts appear in the blood. But when liver is removed no accumulation takes place. When function of liver is depressed by injury or by the establishment of Eck’s fistula (Portal vein is connected with inferior vena cava, so that portal blood does not go through liver), the output of bile salts is reduced by 50%.
These evidences show that synthesis of bile salts takes place probably only in the liver. When cholic acid is administered, along with enough taurine and glycine the concentration of bile salts in the bile increases. With a high protein diet the amount of bile salts increases. With carbohydrate, their concentration is lowered.
Mechanism of Synthesis:
Glycine is a simple amino acid which is synthesised in the body. Taurine is derived from sulphur-containing amino acid, cysteine. Glycocholic and taurocholic acids are formed by the combination of glycine and taurine with cholic acid respectively.
The reaction is represented as follows:
1. Cholic acid + CoA + ATP → Cholyl CoA + AMP + PPi
2. Cholyl CoA + Glycine → Cholyl glycine conjugate + CoA.
The second enzyme similarly catalyses conjugation with taurine forming cholyl taurine conjugate. Because of the alkalinity of bile a major part of the conjugated bile acids forms salts with sodium or potassium, the glycocholates or taurocholates.
Enterohepatic Circulation and Fate of Bile Salts:
When all bile from the common bile duct is collected by a cannula, it is seen that bile salts given by mouth can be quantitatively recovered from the bile in six hours. From these observations it is clear that bile salts are mostly (80 – 90%) reabsorbed from the intestine and are re-excreted in the bile.
A number of other substances are excreted in the bile along with bile salts and most of them act as choleretics. This cyclical migration of the bile salts is called enterohepatic circulation. At each cycle a small part is lost in the faeces, which makes about 10 – 20% of the total amount. Normally, liver synthesises only this lost amount to keep up the usual quantity.
Functions of Bile Salts:
Most of the important functions of bile are due to the presence of bile salts. It will be seen that, as the bile salts run in the enterohepatic circulation, they serve some important functions at each step.
The functions may be summarised as follows step by step:
1. While Present in Bile (i.e., in Liver and Bile Channels):
Bile salts keep insoluble cholesterol in solution (by hydrotropic action). The normal ratio between cholesterol and bile salts in the bile, varies from 1: 20 to 1 : 30. When this ratio falls to 1:13 cholesterol is precipitated and forms gall-stones (Best and Taylor). Others put the ratio at a much lower figure, viz., 1 : 8, which is actually found to be the ratio between cholesterol and bile acids in samples of bile, containing gall-stones. The ratio in normal bile is usually above this (Thorpe). Biliary stasis and infection of gall-bladder are the factors contributing the formation of gall-stone.
2. While Present in the Intestine:
They subserve the following function:
a. Digestion of Fats:
Digestion of fats and to some extent of other foodstuffs. This is done in three ways – first, by reducing surface tension of water, fat is emulsified, thus rendering larger surface area for the enzymes to act; secondly, by activating the lipases directly and thus increasing their actions; and thirdly, due to their presence, bile acts as a good solvent for the otherwise insoluble substances, viz., fatty acid and water-insoluble soaps, and in this way, acts as a suitable medium facilitating the interaction between fats and the fat-splitting enzymes.
b. Absorption of:
(a) Fats and partly other foodstuffs;
(b) Iron, calcium and probably other minerals, and also of
(c) The fat soluble vitamins -A, D, E and K; and pro-vitamin carotene.
c. Increase Peristalsis:
Increase peristalsis of both small and large intestine and thus acts as a laxative.
d. Impairment of Fat:
Impairment of fat digestion results impairment of digestion of other food substances, since fat, covering the food particles, prevents enzymes from attacking them. Under these conditions, the intestinal bacteria cause much putrefaction and production of gas.
e. While Being Reabsorbed from the Intestine:
They exert hydrotropic action upon the insoluble substances and thus help their absorption. The insoluble fatty acid is absorbed as fatty acid bile-salt complex (choleic acid).
f. While Inside the Epithelium:
After entering the epithelium, the conjugated compounds break down and the bile salts become free. A part of it goes back to the surface of the epithelium to carry further loads of fat. In this way this part of bile salts remains within the epithelium and moves like a shuttle carrying fresh loads of fatty acids repeatedly. But the main part enters the portal circulation and is carried back to liver.
g. While Back to Liver:
The bile salts act as the strongest cholagogues and thus stimulate bile secretion.