Digestion of lipids- Lecture notes

Introduction

Lipids are a heterogeneous group of water-insoluble organic molecules that can be extracted from tissues by non-polar solvents. They are the major source of energy for the body.

Dietary fat Composition

More than 95% are triglycerides, the other are -Cholesteryl esters, phospholipids, and unesterified fatty acids.

Dietary sources of Lipids

a) Animal Sources

• Dairy products- Milk, butter, ghee
• Meat, fish, pork, and eggs

b) Vegetable Sources

• Cooking oils- Sunflower oil, Mustard oil, Groundnut oil
• Fats from other vegetable sources.

 Enzymes of lipid digestion

• Lipases- for the digestion of triglycerides
• Phospholipase A2- for the digestion of Phospholipids
• Cholesterol esterase-For the digestion of Cholesteryl esters

Lipases

Three main lipases

• Lingual
• Gastric and
• Pancreatic

 The general reaction catalyzed by lipase

Triglycerides are degraded by lipases to form free fatty acids and glycerol. The reaction proceeds in a stepwise manner (figure-1).

Figure-1-Triglycerides are degraded by lipases to form free fatty acids and glycerol

A) Digestion in Mouth

Hydrolysis of triacylglycerols is initiated by lingual and gastric lipases, which attack the sn-3 ester bond-forming 1,2-diacylglycerols and free fatty acids, aiding emulsification.

Lingual lipase:

Characteristics

• Secreted by dorsal surface of the tongue
• Active at low pH (pH 2.0 – 7-5)
• Optimum pH 4.0-4.5
• Ideal substrate-Short chain TGS
• Milk fat contains short-chain fatty acids which are esterified at -3 position, thus it is the best substrate for lingual lipase
• Enzymatic action continues in the stomach
• Short-chain fatty acids, released are absorbed directly from the stomach wall and enter the portal vein.

B) Digestion in Stomach

• Gastric Lipase is secreted in small quantities
• More effective at alkaline pH (vaerage p H 7.8)
• Requires the presence of Ca⁺⁺
• Less effective in stomach due to acidic pH except when intestinal contents are regurgitated into the gastric lumen
• Not effective for long-chain fatty acids, most effective for short and medium-chain fatty acids
• Milk, egg yolk and fats containing short-chain fatty acids are suitable substrates for its action

Role of fats in gastric emptying

• Fats delay the rate of emptying of the stomach
• Action is brought about by secretion of Enterogastrone
• Enterogastrone inhibits gastric motility and retards the discharge of bolus of food from the stomach.
• Thus fats have a high satiety value.

Significance of Lingual and Gastric Lipases

• Play an important role in lipid digestion in neonates since milk is the main source of energy
•  Important digestive enzymes in pancreatic insufficiency such as Cystic fibrosis or other pancreatic disorders
•  Lingual and gastric lipases can degrade triglycerides with short and medium-chain fatty acids in  patients  with pancreatic disorders despite a near or complete absence of pancreatic lipase

Emulsification and digestion

• Lipids are hydrophobic, and thus are poorly soluble in the aqueous environment of the digestive tract. 
•  The digestive enzyme, lipase, is water-soluble and can only work at the surface of fat globules. 
• Digestion is greatly aided by emulsification, the breaking up of fat globules into much smaller emulsion droplets.
• Triacylglycerol digestion occurs at lipid-water interfaces
•  Rate of TAG digestion depends on the surface area of this interface which is increased by churning peristaltic movements of the intestine,
• combined with the emulsifying action of bile salts
• The critical process of emulsification takes place in the duodenum.

C) Digestion in the small intestine

• The major site of fat digestion
•  Effective digestion due to the presence of Pancreatic lipase and bile salts.
•  Bile salts act as effective emulsifying agents for fats
•  Secretion of pancreatic juice is stimulated by-

•  Passage of acid gastric contents into the duodenum
• By secretion of Secretin, Cholecystokinin and Pancreozymin, the gastrointestinal hormones

Gastro-Intestinal hormones

• Secretin- increases the secretion of electrolytes and fluid components of pancreatic juice
• Pancreozymin of CCK -PZ stimulates the secretion of the pancreatic enzymes
• Cholecystokinin of CCK-PZ- causes the contraction of the gall bladder and discharges the bile into the duodenum.
• Hepatocrinin- Released by the intestinal mucosa, it stimulates more bile formation which is relatively poor in bile acid content.

Contents of Pancreatic Juice

• Pancreatic Lipase- For the digestion of triglycerides
•  Phospholipase A2- for the digestion of Phospholipids
• Cholesterol esterase-For the digestion of Cholesteryl esters

 Role of Bile Salts

• Bile salts are required for the proper functioning of the pancreatic lipase enzyme
• Bile salts help in a combination of lipase with two molecules of a small protein called Colipase. This combination enhances the lipase activity.
•  Bile salts also help in the emulsification of fats
• Bile salts are synthesized in the liver and stored in the gall bladder
•  They are derivatives of cholesterol
•  They consist of a sterol ring structure with a side chain to which a molecule of glycine or Taurine is covalently attached by an amide linkage(figure-2).

Figure-2- Bile salts are derivatives of cholesterol contain a sterol ring structure with a side chain to which a molecule of glycine or Taurine is covalently attached by an amide linkage.

• Bile salts are formed from bile acids
• The primary bile acids are cholic acid (found in the largest amount) and chenodeoxycholic acid.
• The primary bile acids enter the bile as glycine or taurine conjugates.
• In the alkaline bile, the bile acids and their conjugates are assumed to be in a salt form—hence the term “bile salts.“

Enterohepatic circulation of Bile salts

The bile salts present in the body are not sufficient to fully process the fats in a typical meal, thus they need to be recycled.  This is achieved by the enterohepatic circulation.  Specific transporters in the terminal ileum move bile salts from the lumen of the digestive tract to the intestinal capillaries. They are then transported directly to the liver via the hepatic portal vein.  Hepatocytes take up bile salts from the blood and increase the secretion of bile salts into the bile canaliculi, small passageways that convey bile into the larger bile ducts.  95% of the bile that is released to the small intestine is recycled via the enterohepatic circulation, while 5% of the bile salts are lost in the feces (figure-3).

Emulsification by bile salts

Bile salts as emulsifying agents interact with the dietary lipid particles and the aqueous duodenal contents, thereby stabilizing the lipid particles as they become smaller, and preventing them from coalescing (figure-4).

Triacyl glycerol degradation by pancreatic lipase(figure-5)

• Pancreatic lipase is specific for the hydrolysis of primary ester linkages(Fatty acids present at position 1 and 3)
• It cannot hydrolyze the ester linkages of position -2
• Digestion of Triglycerides proceeds by the removal of a terminal fatty acid to produce an α,β
• The other terminal fatty acid is then removed to produce β
• The last fatty acid is linked by secondary ester group, hence cannot be hydrolyzed by pancreatic lipase.
•  β- Mono acyl glycerol can be converted to α- Mono acyl glycerol by isomerase enzyme and then hydrolyzed by Pancreatic lipase.
• The primary product of hydrolysis are β- Mono acyl glycerol (78%), α- Mono acyl glycerol (6%) with free fatty acids and glycerol (14%).

 

Figure-3-Enterohepatic circulation of bile salts              

Figure-4- Role of bile salts in emulsification

Figure-5- Triglyceride digestion by pancreatic lipase.

Summary of Emulsification and Digestion of Triglycerides

Figure-6- steps of emulsification and digestion of dietary triglycerides.

Significance of Pancreatic lipase

• The enzyme is present in high concentrations in the pancreas. Only very severe pancreatic deficiency such as cystic fibrosis results in malabsorption of fats due to impaired digestion.
•  Orlistat, an anti-obesity drug inhibits gastric and pancreatic lipases, thereby decreasing fat digestion and absorption resulting in weight loss.

Cholesteryl ester degradation

• Dietary cholesterol is mainly present in the free (Non-esterified) form
• Only 10-15% is present in the esterified form
• Cholesteryl esters are hydrolyzed by pancreatic Cholesteryl esterase (Cholesterol ester Hydrolase) to produce cholesterol and free fatty acid
• The enzymatic activity is greatly increased in the presence of bile salts.

 

Figure-7- degradation of cholesteryl esters.

Phospholipid degradation

• The enzyme – Phospholipase A₂ requires bile salts for optimum activity.
• Removes one fatty acid from carbon 2 of Phospholipid to form lysophospholipid.
• The remaining fatty acid at position 1  can be removed by lysophospholipase, leaving a glyceryl phosphoryl base that may be excreted in the feces, further degraded or absorbed.

Figure-7- Degradation of Phospholipids.