Digestion and Transport of Dietary Lipids

Triacylglycerols are the major fat in the human diet, consisting of three fatty acids esterified to a glycerol backbone. Limited digestion of these lipids occurs in the mouth (lingual lipase) and stomach (gastric lipase) because of the low solubility of the substrate. In the intestine, however, the fats are emulsified by bile salts that are released from the gallbladder. This increases the available surface area of the lipids for pancreatic lipase and colipase to bind and to digest the triglycerides. Degradation products are free fatty acids and 2-monoacylglycerol. When partially digested food enters the intestine, the hormone cholecystokinin is secreted by the intestine, which signals the gallbladder to contract and release bile acids, and the pancreas to release digestive enzymes.

In addition to triacylglycerols, phospholipids, cholesterol, and cholesterol esters (cholesterol esterified to fatty acids) are present in the foods we eat. Phospholipids are hydrolyzed in the intestinal lumen by phospholipase A2, and cholesterol esters are hydrolyzed by cholesterol esterase. Both of these enzymes are secreted from the pancreas.

The products of enzymatic digestion (free fatty acids, glycerol, lysophospholipids, and cholesterol) form micelles with bile acids in the intestinal lumen. The micelles interact with the enterocyte membrane and allow diffusion of the lipid-soluble components across the enterocyte membrane into the cell. The bile acids, however, do not enter the enterocyte at this time. They remain in the intestinal lumen, travel farther down, and are then reabsorbed and sent back to the liver by the enterohepatic circulation. This allows the bile salts to be used multiple times in fat digestion.

The intestinal epithelial cells resynthesize triacylglycerol from free fatty acids and 2-monoacylglycerol and package them with a protein, apolipoprotein B-48, phospholipids, and cholesterol esters into a soluble lipoprotein particle known as a chylomicron. The chylomicrons are secreted into the lymph and eventually end up in the circulation, where they can distribute dietary lipids to all tissues of the body.

Once they are in the circulation, the newly released (“nascent”) chylomicrons interact with another lipoprotein particle, high-density lipoprotein (HDL), and acquire two apolipoproteins from HDL, apolipoprotein CII (apoCII) and apolipoprotein E (apoE). This converts the nascent chylomicron into a “mature” chylomicron. The apoCII on the mature chylomicron activates the enzyme lipoprotein lipase (LPL), which is located on the inner surface of the capillary endothelial cells of muscle and adipose tissue. The LPL digests the triglyceride in the chylomicron, producing free fatty acids and glycerol. The fatty acids enter the adjacent organs either for energy production (muscle) or for fat storage (adipocyte). The glycerol that is released is metabolized in the liver.

As the chylomicron loses triglyceride, its density increases and it becomes a chylomicron remnant, which is taken up by the liver by receptors that recognize apoE. In the liver, the chylomicron remnant is degraded into its component parts for further disposition by the liver.


Will S. has had several episodes of mild back and lower extremity pain over the last year, probably caused by minor sickle cell crises. He then developed abdominal pain in the right upper quadrant. He states that the pain is not like his usual crisis pain. Intractable vomiting began 12 hours after the onset of these new symptoms and he then went to the emergency department.

On physical examination, his body temperature is slightly elevated and his heart rate is rapid. The whites of his eyes (the sclerae) are slightly jaundiced (or icteric, a yellow discoloration caused by the accumulation of bilirubin pigment). He is exquisitely tender to pressure over his right upper abdomen.

The emergency department physician suspects that Will S. is not in sickle cell crisis but instead has acute cholecystitis (gallbladder inflammation). His hemoglobin level is low at 7.6 mg/dL (reference range, 12 to 16 mg/dL), but is unchanged from his baseline 3 months earlier. His serum total bilirubin level is 2.3 mg/dL (reference range, 0.2 to 1.0 mg/dL), and his direct (conjugated) bilirubin level is 0.9 mg/dL (reference range, 0 to 0.2 mg/dL).

Intravenous fluids were started, he was not allowed to take anything by mouth and symptomatic therapy was started for pain and nausea. He was sent for an ultrasonographic (ultrasound) study of his upper abdomen.

Al M. has continued to drink alcohol and to eat poorly. After a particularly heavy intake of vodka, a steady severe pain began in his upper midabdomen. This pain spread to the left upper quadrant and eventually radiated to his midback. He began vomiting nonbloody material and was brought to the hospital emergency department with fever, a rapid heartbeat, and a mild reduction in blood pressure. On physical examination, he was dehydrated and tender to pressure over the upper abdomen. His vomitus and stool were both negative for occult blood.

Blood samples were sent to the laboratory for a variety of hematologic and chemical tests, including a measurement of serum lipase, one of the digestive enzymes that is normally secreted from the exocrine pancreas through the pancreatic ducts into the lumen of the small intestine.

I. Digestion of Triacylglycerols

Triacylglycerols are the major fat in the human diet because they are the major storage lipid in the plants and animals that constitute our food supply. Triacylglycerols contain a glycerol backbone to which three fatty acids are esterified (Fig. 29.1). The main route for digestion of triacylglycerols involves hydrolysis to fatty acids and 2-monoacylglycerol in the lumen of the intestine. However, the route depends to some extent on the chain length of the fatty acids. Lingual and gastric lipases are produced by cells at the back of the tongue and in the stomach, respectively. These lipases preferentially hydrolyze short- and medium-chain fatty acids (containing 12 or fewer carbon atoms) from dietary triacylglycerols. Therefore, they are most active in infants and young children who drink relatively large quantities of cow’s milk, which contains triacylglycerols with a high percentage of short- and medium-chain fatty acids.

FIGURE 29.1 Structure of a triacylglycerol. The glycerol moiety is highlighted, and its carbons are numbered.

A. Action of Bile Salts

Dietary fat leaves the stomach and enters the small intestine, where it is emulsified (suspended in small particles in the aqueous environment) by bile salts (Fig. 29.2). The bile salts are amphipathic compounds (containing both hydrophobic and hydrophilic components), synthesized in the liver (see Chapter 32 for the pathway) and secreted via the gallbladder into the intestinal lumen. The contraction of the gallbladder and secretion of pancreatic enzymes are stimulated by the gut hormone cholecystokinin, which is secreted by the intestinal cells when stomach contents enter the intestine. Bile salts act as detergents, binding to the globules of dietary fat as they are broken up by the peristaltic action of the intestinal muscle. This emulsified fat, which has an increased surface area compared with unemulsified fat, is attacked by digestive enzymes from the pancreas (Fig. 29.3).

FIGURE 29.2 Structure of a bile salt. The bile salts are derived from cholesterol and retain the cholesterol ring structure. They differ from cholesterol in that the rings in bile salts contain more hydroxyl groups and a polar side chain and lack a C5–C6 double bond.

FIGURE 29.3 Digestion of triacylglycerols in the intestinal lumen. Prior to reaching the intestine, lingual lipase (mouth) and gastric lipase (stomach) have begun digestion of the triacylglycerol. 2-MG, 2-monoacylglycerol; bs, bile salts; FA, fatty acid; TG, triacylglycerol.

B. Action of Pancreatic Lipase

The major enzyme that digests dietary triacylglycerols is a lipase produced in the pancreas. Pancreatic lipase is secreted along with another protein, colipase, in response to the release of cholecystokinin from the intestine. The peptide hormone secretin is also released by the small intestine in response to acidic materials (such as the partially digested materials from the stomach, which contains HCl) entering the duodenum. Secretin signals the liver, pancreas, and certain intestinal cells to secrete bicarbonate. Bicarbonate raises the pH of the contents of the intestinal lumen into a range (pH ~6) that is optimal for the action of all of the digestive enzymes of the intestine.

Bile salts inhibit pancreatic lipase activity by coating the substrate and not allowing the enzyme access to it. The colipase binds to the dietary fat and to the lipase, relieving the bile salt inhibition and allowing triglyceride to enter the active site of the lipase. This enhances lipase activity. Pancreatic lipase hydrolyzes fatty acids of all chain lengths from positions 1 and 3 of the glycerol moiety of the triacylglycerol, producing free fatty acids and 2-monoacylglycerol—that is, glycerol with a fatty acid esterified at position 2 (Fig. 29.4). The pancreas also produces esterases that remove fatty acids from compounds (such as cholesterol esters) and phospholipase A2 (which is released in its zymogen form and is activated by trypsin) that digests phospholipids to a free fatty acid and a lysophospholipid (see Fig. 29.4B and C).

FIGURE 29.4 Action of pancreatic enzymes on fatty acid digestion. A. Action of pancreatic lipase. FAs are cleaved from positions 1 and 3 of the triacylglycerol, and a monoacylglycerol with a fatty acid at position 2 is produced. B. Action of pancreatic cholesterol esterase. C. Action of phospholipase A2. FA, fatty acid.

II. Absorption of Dietary Lipids

The fatty acids and 2-monoacylglycerols produced by digestion are packaged into micelles, tiny microdroplets that are emulsified by bile salts (see Fig. 29.3). For bile salt micelles to form, the concentration of bile salts in the intestinal lumen must reach 5 to 15 mM (the critical micelle concentration [CMC]). Below this concentration the bile salts are soluble; above it, micelles will form. Other dietary lipids, such as cholesterol, lysophospholipids, and fat-soluble vitamins, are also packaged in micelles. The micelles travel through a layer of water (the unstirred water layer) to the microvilli on the surface of the intestinal epithelial cells, where the fatty acids, 2-monoacylglycerols, and other dietary lipids are absorbed, but the bile salts are left behind in the lumen of the gut.

The bile salts are extensively resorbed when they reach the ileum. Greater than 95% of the bile salts are recirculated, traveling through the enterohepatic circulation to the liver, which secretes them into the bile for storage in the gallbladder and ejection into the intestinal lumen during another digestive cycle (Fig. 29.5).

FIGURE 29.5 Recycling of bile salts. Bile salts are synthesized in the liver, stored in the gallbladder, secreted into the small intestine, resorbed in the ileum, and returned to the liver via the enterohepatic circulation. Under normal circumstances, 5% or less of luminal bile acids are excreted in the stool.

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Aug 7, 2022 | Posted by in BIOCHEMISTRY | Comments Off on Digestion and Transport of Dietary Lipids
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