Localization and conditions of lipid digestion
Human lipid digestion begins exclusively in the lumen of the small intestine. Fat hydrolysis practically does not occur in the oral cavity and stomach because the conditions for lipolytic enzymes are absent: lipids are insoluble in water, and the gastric environment is acidic. Two key conditions are created in the small intestine — alkaline pH and fat emulsification.
The alkaline environment is maintained by bicarbonate ions secreted by the pancreas. Bicarbonates neutralize protons coming from the stomach via the reaction: H⁺ + HCO₃⁻ → H₂CO₃ → H₂O + CO₂. Carbon dioxide is eliminated, and the medium pH shifts toward the alkaline side, which is optimal for pancreatic enzymes.
Emulsification of fats by bile acids
The liver synthesizes and secretes bile acids and their salts as part of bile, which enter the duodenum. Bile acids perform several functions:
- emulsify dietary fats by breaking them down into small droplets and drastically increasing the contact surface area with the enzyme;
- activate colipase, a protein cofactor of pancreatic lipase;
- are incorporated into mixed micelles, which ensure the transport of hydrolysis products to enterocytes.
Without emulsification, the efficiency of lipolysis drops sharply, since lipase is able to work only at the water–lipid interface.
Action of pancreatic lipase
The main enzyme for the hydrolysis of dietary triacylglycerols is pancreatic lipase. For its activity to manifest, it requires an alkaline pH and binding to colipase, which anchors the enzyme to the surface of the emulsion droplet and prevents its inhibition by bile acids.
Pancreatic lipase selectively hydrolyzes ester bonds at positions 1 and 3 of the triacylglycerol molecule, without affecting the bond at the 2nd position. As a result, the following are formed:
- 2-monoacylglycerol (β-monoacylglycerol) — the main product;
- two free fatty acids;
- diacylglycerol as an intermediate product.
Formation of mixed micelles
Hydrolysis products, together with bile acids, spontaneously form mixed micelles — water-soluble supramolecular structures. The composition of a mixed micelle includes:
- 2-monoacylglycerols and free fatty acids;
- bile acids as surface-active components;
- cholesterol;
- fat-soluble vitamins — A, D, E, K.
Biological role of fat-soluble vitamins: A is a component of the visual pigment, D is a regulator of calcium and phosphorus metabolism, E is an antioxidant that inhibits lipid peroxidation, and K is a cofactor for γ-carboxylation of blood clotting factors.
Mixed micelles deliver hydrophobic components to the brush border of enterocytes, where they disintegrate, and lipid molecules enter the cells. Bile acids are mostly absorbed in the ileum and returned to the liver as part of the enterohepatic circulation.
Activation of fatty acids in enterocytes
Before being used in biosynthesis, fatty acids undergo obligatory activation. The reaction is catalyzed by the enzyme acyl-CoA synthetase and is coupled with the cleavage of two high-energy ATP bonds (ATP → AMP + PPi):
R–COOH + HS-CoA + ATP → R–CO~S-CoA (acyl-CoA) + AMP + PPi
The resulting thioester bond between the fatty acid residue and coenzyme A is high-energy and provides the energy for subsequent acylation reactions.
Resynthesis of triacylglycerols and formation of chylomicrons
In enterocytes, fat resynthesis takes place from the absorbed components. Two acyl-CoA residues are sequentially attached to the 2-monoacylglycerol molecule with the release of free HS-CoA; ultimately, triacylglycerol is formed.
Crucially, the resynthesized triacylglycerols differ from dietary ones in their fatty acid composition: they incorporate fatty acids characteristic of the human body. Thus, "adaptation" of dietary fats to one's own metabolism occurs.
Resynthesized triacylglycerols, along with cholesterol, phospholipids, and apoproteins, are packaged into chylomicrons — large transport lipoproteins. Chylomicrons are secreted into the lymph, then pass through the thoracic lymphatic duct into the bloodstream and deliver exogenous lipids to tissues.
Key points
- Lipid digestion is localized in the small intestine and requires an alkaline pH maintained by pancreatic bicarbonates.
- Bile acids emulsify fats, activate colipase, and form mixed micelles.
- Pancreatic lipase complexed with colipase hydrolyzes bonds at positions 1 and 3 of triacylglycerol to form 2-monoacylglycerol and two fatty acids.
- Cholesterol and fat-soluble vitamins A, D, E, K are also absorbed as part of mixed micelles.
- Activation of fatty acids is catalyzed by acyl-CoA synthetase with the expenditure of two high-energy ATP bonds.
- Triacylglycerols resynthesized in enterocytes differ in composition from dietary fats.
- The transport of exogenous lipids from the intestine to tissues is carried out by chylomicrons via the lymphatic system.