What are Bile Salts: Structure, Synthesis and Types

Bile salts are essential for ensuring optimal lipid digestion and absorption. Bile salts are among the components present in the greenish-yellow fluid known as bile. Bile gets secreted by the liver using the classic, neutral, or acidic pathway, and is subsequently stored in the gallbladder. Bile salts also help absorb fat-soluble vitamins like A, D, E, and K and remove toxic substances.

• Bile acids undergo numerous cycles of recycling each day through the enterohepatic circulation.
• A deficiency of bile salts causes several health issues in human beings.
• Impaired bile salt transport by hepatocytes results in the condition called cholestasis.
• Bile-acid diarrhea develops as a result of a heightened presence of bile acids in the colon.
• It also boosts the risk of forming gallstones, kidney stones, and irritable bowel syndrome.
• Inadequate production and storage of bile salts may cause diarrhea, trapped gas, noxious-smelling gas, stomach cramps, unpredictable bowel movements, weight loss, and pale-colored stools.

Key Terms: Bile, Bile Salts, Liver, Gallbladder, Hepatic Duct, Cholesterol, Bilirubin, Enterohepatic Circulation, Lipid Digestion, Emulsification

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What is Bile?

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Bile is a greenish-yellow fluid substance secreted by the liver and stored in the gallbladder. It is composed of different substances like bile salts, bile acids, conjugated bilirubin, phospholipids, cholesterol, water, and some electrolytes. The bile enters the gallbladder through the common hepatic duct. The primary function of bile juice is to help in the digestion of lipids (emulsification of lipids).

Bile

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What are Bile Salts?

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Bile salts form an essential ingredient in bile fluid. Bile salts help in the digestion of fats, and absorption of fat-soluble vitamins like A, D, E, and K. Bile acids and taurine or glycine binding lead to the generation of bile salts in vertebrates.

• The role of bile salts extends to hepatobiliary functions, intestinal digestion, and maintaining homeostasis.
• Cholesterol is transformed into primary bile salts within the liver through enzymatic reactions.
• Secondary and tertiary bile salts arise as primary bile salts undergo modifications.

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Structure of Bile Salts

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The bile salts have a central steroid nucleus with hydroxyl or other substituents. They may also have an aliphatic side chain of varied lengths. In vertebrate animals, the carbon backbone is usually 24 carbons long. In non-vertebrate animals, the carbon backbone is 25-27 carbons long.

Structure of Bile Salts

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Synthesis of Bile Salts

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Synthesis of bile salts occurs in the liver's hepatocytes, converting cholesterol through the classic or neutral pathway. It is formed from cholesterol using up to 17 enzymes in the cell organelles like the endoplasmic reticulum, mitochondria, peroxisomes, and cytosol. The rate-controlling stage of the classic pathway is the 7α-hydroxylation of cholesterol, managed by microsomal cytochrome P-450 monooxygenase.

• The alternative pathway for bile salt synthesis is called the acidic pathway.
• This is initiated by a mitochondrial enzyme called 27-hydroxylase. Cholate (C) and chenodeoxycholate (CDC) are the main primary outcomes of bile production.
• The primary bile salt (dehydroxylation at C-7 of C or CDC) is modified with bacterial enzymes to form secondary bile salts called deoxycholate (DC) and lithocholic (LC).
• The C7 position of CDC will be epimerized to form tertiary bile salts called ursodeoxycholate (UDC).

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Types of Bile Salts

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The primary bile salts are cholate (C) and chenodeoxycholate (CDC). The secondary bile salts are deoxycholate (DC) and lithocholate (LC). The tertiary bile salts are ursodeoxycholate (UDC).

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Chemical Properties of Bile Salts

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In the bile, bile salts are available at the physiological pH as the pKa of glycine-conjugated salts commonly ranges from 4-5; taurine-conjugated salts are 1. UDC is the most hydrophobic bile salt followed by C, CDC, DC, and LC in bile. Taurine-linked bile salts exhibit higher hydrophilicity compared to those conjugated with glycine.

Enterohepatic circulation of the bile acids

The human body produces around 800 mg of cholesterol every day. Half (almost 400mg) of the amount is utilized for bile acid production. 

• 12-18 g of bile acids are secreted in the intestines after eating. 
• The total amount of bile acids in the pool is merely 4-6 grams.
•  Recycling processes for bile acids take place several times daily.
• Almost 95% of the bile acids are actively absorbed in the ileum region, recycled, and sent back to the liver. 
• The term used to describe this process is the enterohepatic circulation of bile acids.

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The function of Bile Salts

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Here are the key functions of bile salts:

Lipid Digestion

Due to the hydrophobic and hydrophilic properties of bile salts, micelles are at the lipid-water interface. Bile salts are not reabsorbed in the small intestine due to their highly soluble nature. 

• Consequently, there is an Accumulation of bile acids/salts in the small intestine. 
• This helps in the solubilization of lipid molecules. 
• The micelles help the lipases in the digestion of lipids.
• The digested lipids that come close to the intestinal brush border get absorbed.

Lipid Digestion

Excretion

The bile salts help in the removal of toxic substances. Toxins that are secreted into the bile are eliminated through feces. A lack of bile salts builds up toxins in the body.

Other Functions

• Elimination of cholesterol from the body
• Elimination of certain catabolites.
• Absorption of fat-soluble vitamins through emulsification
• Acts as a medium for the motility of bacterial flora in the intestinal tract
• Regulation of the activity of some enzymes and ion channels

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Clinical Significance

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• Cholestasis: When hepatocytes encounter difficulties in transporting bile salts, it results in cholestasis. It results in reduced bile flow and retention of biliary constituents in the liver and serum. This is manifested in biochemical and morphological changes in the body.
• Bile-acid diarrhea: A high concentration of bile acids in the colon leads to bile-acid diarrhea. This is due to the malabsorption of bile acid in the ileum. It can be surgically removed.
• Kidney stones: Bile salt deficiency may increase the risk of forming kidney stones and gallstones, Crohn’s disease, and irritable bowel syndrome.
• Other Complications: Inadequate bile salt production and storage could result in symptoms including diarrhea, trapped gas, odorous gas, stomach cramps, irregular bowel movements, weight loss, and pale-colored stools.

Bile salts are the primary components of bile. Bile salts are stored in the gallbladder. They are helpful in fat digestion and absorption of fat-soluble vitamins. Bile salt deficiency leads to various kinds of digestive problems.

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Things to Remember

• Bile is a greenish-yellow fluid substance secreted by the liver and stored in the gallbladder.
• The primary function of bile juice is to help in the digestion of lipids.
• Bile salts also help in the absorption of fat-soluble vitamins like A, D, E, and K.
• The bile salts have a central steroid nucleus with hydroxyl or other substituents.
• The bile salts are synthesized through the classic or neutral pathway. The acidic pathway is referred to as the alternate route.
• Through the enterohepatic circulation process, bile acids experience multiple rounds of recycling daily.
• Bile salts help in the removal of toxic substances.
• Cholestasis is characterized by the compromised transport of bile salts by hepatocytes.
• Bile-acid diarrhea develops as a result of a heightened existence of bile acids in the colon.
• Bile salt deficiency may increase the risk of forming kidney stones and gallstones, Crohn’s disease, and irritable bowel syndrome.
• The absence of proper bile salt production and storage could contribute to issues like diarrhea, trapped gas, malodorous gas, stomach cramps, erratic bowel movements, weight loss, and pale stools.

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