Cholesteryl ester degradation primarily occurs in the free form, with a small portion being in the esterified form. The pancreatic enzyme cholesteryl ester hydrolase, also known as cholesterol esterase, breaks down cholesteryl esters, resulting in the production of cholesterol and free fatty acids. Bile salts significantly enhance the activity of this enzyme.

The degradation of phospholipids is facilitated by the proenzyme of phospholipase A2 found in pancreatic juice. Similar to cholesteryl ester hydrolase, phospholipase A2 requires bile salts for optimal activity and is activated by trypsin. This enzyme removes a fatty acid from carbon 2 of a phospholipid, leaving a lysophospholipid. The predominant phospholipid, phosphatidylcholine, is transformed into lysophosphatidylcholine. The remaining fatty acid at carbon 1 can be removed by lysophospholipase, resulting in a glycerylphosphoryl base such as glycerylphosphorylcholine, which can be excreted in the feces, further degraded, or absorbed.

The release of hydrolytic enzymes involved in lipid digestion in the small intestine is hormonally regulated. Cholecystokinin (CCK), produced by cells in the mucosa of the lower duodenum and jejunum, is stimulated by the presence of lipids and partially digested proteins. CCK induces the contraction of the gallbladder, leading to the release of bile into the small intestine. Additionally, CCK stimulates the exocrine cells of the pancreas to secrete digestive enzymes. It also reduces gastric motility, resulting in a slower release of gastric contents into the small intestine. Secretin, another peptide hormone produced by intestinal cells, is released in response to the low pH of chyme from the stomach entering the intestine. Secretin prompts the pancreas to secrete a bicarbonate-rich solution, which helps neutralize the pH of the intestinal contents, creating an appropriate environment for pancreatic enzyme activity.

In the jejunum, the primary products of lipid digestion are free fatty acids, free cholesterol, and 2-MAG. These, along with bile salts and fat-soluble vitamins (A, D, E, and K), form mixed micelles. These micelles, which consist of amphipathic lipids, are soluble in the watery environment of the intestinal lumen. They approach the brush border membrane of the enterocytes, where the majority of lipid absorption takes place. The brush border membrane, which is rich in microvilli, is separated from the liquid contents of the intestine by an unstirred water layer. The hydrophilic surface of the micelles aids in transporting the hydrophobic lipids through this layer to the brush border membrane for absorption. Bile salts are absorbed in the terminal ileum, with less than 5% being eliminated in the feces. It is worth noting that compared to other dietary lipids, cholesterol is poorly absorbed by enterocytes. Drug therapy, such as the use of ezetimibe, can further decrease cholesterol absorption in the small intestine. Short- and medium-chain fatty acids, being water-soluble, do not require mixed micelles for absorption by the intestinal mucosa.
Cholesteryl ester degradation: Most dietary cholesterol is present in the free (nonesterified) form, with 10%–15% present in the esterified form. Cholesteryl esters are hydrolyzed by pancreatic cholesteryl ester hydrolase (cholesterol esterase), which produces cholesterol plus FFA (see Fig. 15.2). Activity of this enzyme is greatly increased in the presence of bile salts.
3.
Phospholipid degradation: Pancreatic juice is rich in the proenzyme of phospholipase A2 that, like procolipase, is activated by trypsin and, like cholesteryl ester hydrolase, requires bile salts for optimum activity. Phospholipase A2 removes one FA from carbon 2 of a phospholipid, leaving a lysophospholipid. For example, phosphatidylcholine (the predominant phospholipid of digestion) becomes lysophosphatidylcholine. The remaining FA at carbon 1 can be removed by lysophospholipase, leaving a glycerylphosphoryl base (for example, glycerylphosphorylcholine, see Fig. 15.2) that may be excreted in the feces, further degraded, or absorbed.
4. Control: Pancreatic secretion of the hydrolytic enzymes that degrade dietary lipids in the small intestine is hormonally controlled (Fig. 15.4). Cells in the mucosa of the lower duodenum and jejunum produce the peptide hormone cholecystokinin (CCK), in response to the presence of lipids and partially digested proteins entering these regions of the upper small intestine. CCK acts on the gallbladder (causing it to contract and release bile, a mixture of bile salts, phospholipids, and free cholesterol) and on the exocrine cells of the pancreas (causing them to release digestive enzymes). It also decreases gastric motility, resulting in a slower release of gastric contents into the small intestine (see p. 353). Other intestinal cells produce another peptide hormone, secretin, in response to the low pH of the chyme entering the intestine from the stomach. Secretin causes the pancreas to release a solution rich in bicarbonate that helps neutralize the pH of the intestinal contents, bringing them to the appropriate pH for digestive activity by pancreatic enzymes.
E. Absorption by enterocytes
FFA, free cholesterol, and 2-MAG are the primary products of lipid digestion in the jejunum. These, plus bile salts and fat-soluble vitamins (A, D, E, and K), form mixed micelles (that is, disc-shaped clusters of a mixture of amphipathic lipids that coalesce with their hydrophobic groups on the inside and their hydrophilic groups on the outside). Therefore, mixed micelles are soluble in the aqueous environment of the intestinal lumen (Fig. 15.5). These particles approach the primary site of lipid absorption, the brush border membrane of the enterocytes. This microvilli-rich apical membrane is separated from the liquid contents of the intestinal lumen by an unstirred water layer that mixes poorly with the bulk fluid. The hydrophilic surface of the micelles facilitates the transport of the hydrophobic lipids through the unstirred water layer to the brush border membrane where they are absorbed. Bile salts are absorbed in the terminal ileum, with <5% being lost in the feces. [Note: Relative to other dietary lipids, cholesterol is only poorly absorbed by the enterocytes. Drug therapy (for example, with ezetimibe) can further reduce cholesterol absorption in the small intestine.] Because short-and medium-chain FA are water soluble, they do not require the assistance of mixed micelles for absorption by the intestinal mucosa.