Digestion and absorption of lipids

Preparation for hydrolysis: emulsification

Up to 90% of dietary lipids are triacylglycerols (TAGs). Since fats are hydrophobic and enzymes operate in an aqueous environment, lipids must be prepared. The initial stage of assimilation is emulsification.

Under the influence of peristalsis and bile acids, large fat droplets are broken down into a finely dispersed emulsion. This massively increases the surface area of the fat-water interface, creating optimal conditions for the efficient action of digestive enzymes.

Action of pancreatic lipase

The main stage of digestion takes place in the intestinal lumen under the action of pancreatic lipase. Lipase on its own is unable to firmly attach to the surface of the emulsified fat droplet. It requires a cofactor protein for this — colipase.

Colipase is synthesized in the pancreas in an inactive form and activated in the intestine via partial proteolysis. It acts as a link between the enzyme and the micelle, significantly accelerating hydrolysis.

Pancreatic lipase cleaves ester bonds strictly at the 1st and 3rd positions of TAGs. The reaction yields 2-monoacylglycerol (2-MAG) and two fatty acid molecules. Operating in parallel is phospholipase A2 (activated by trypsin), which hydrolyzes dietary phospholipids, converting them into amphiphilic compounds capable of being absorbed.

Micelle formation and absorption

Lipid hydrolysis products cannot simply dissolve and be absorbed. To cross the aqueous layer of the intestinal mucosa, they assemble into mixed micelles.

These structures comprise:

• 2-monoacylglycerols and fatty acids;
• Bile acids;
• Cholesterol;
• Fat-soluble vitamins.

Mixed micelles deliver lipids to the surface of the intestinal mucosal cells (enterocytes). At the cell membrane, the micelles break down: hydrophobic components diffuse into the enterocyte, while bile acids remain in the intestinal lumen.

Fat resynthesis in enterocytes

Once inside the cell, hydrolysis products do not go straight into the bloodstream. Enterocytes use them as building blocks to assemble their own, body-specific TAG molecules — a process called resynthesis.

1. Fatty acid activation: The enzyme acyl-CoA synthetase attaches coenzyme A to a fatty acid at the expense of an ATP molecule. The active form, acyl-CoA, is formed.
2. TAG assembly: Acyltransferase enzymes sequentially attach Acyl-CoA molecules to 2-MAG.

An important feature of resynthesis is that the cell can use not only dietary fatty acids, but also endogenous ones (synthesized by the body itself). Because of this, the composition of new TAGs always differs from the composition of ingested fats.

Disorders of fat digestion

Impaired lipid digestion most commonly arises from two causes:

• Decreased pancreatic lipase activity (e.g., in pancreatitis).
• Impaired emulsification due to bile deficiency (in cholelithiasis).

The main symptom of lipid malabsorption is steatorrhea (the presence of undigested fats in feces). Prolonged malabsorption inevitably leads to a deficiency of fat-soluble vitamins. Thus, a shortage of vitamin K causes reduced blood clotting speed and bleeding, while vitamin A deficiency leads to night blindness — impaired vision in dim light.

Tissue fat hydrolysis

Resynthesized fats are packaged into chylomicrons and sent into the bloodstream. The breakdown of TAGs within chylomicrons and VLDLs occurs in the capillaries of adipose, muscle, and cardiac tissue.

Here, another enzyme operates — lipoprotein lipase (LPL), located on the endothelium. It is activated by the apoC-II protein and cleaves TAGs into glycerol and three fatty acids. Fatty acids are immediately captured by cells for storage as droplets or oxidation to generate energy.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Stages of chylomicron formation and exocytosis from enterocytes
• Hormonal regulation of TAG lipase in adipocytes
• Mechanism of trypsin-mediated phospholipase A2 activation
• Chemical reactions of the monoacylglycerol pathway of TAG synthesis

Other topics in the «Lipid metabolism» section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.