14.4 The Digestion of Lipids Is Complicated by Their Hydrophobicity

As we eat our pizza, we may notice that the box has greasy stains. These stains are caused by the lipids in our meal. The main sources of lipids in the pizza are the meat and the cheese, which, as already noted, are sources of protein as well. Most lipids are ingested in the form of triacylglycerols and must be degraded to fatty acids for absorption across the intestinal epithelium. Lipid digestion presents a problem because, unlike carbohydrates and proteins, lipids are not soluble in water. Recall that lipids are highly reduced molecules. This high degree of reduction accounts both for their high energy content and for their poor solubility in water (Chapter 11). How can the lipids be degraded to fatty acids if the lipids are not soluble in the same medium as the degradative enzymes are? Moreover, the lipid-digestion products—fatty acids—also are not water soluble; so, when digestion has taken place, how does fatty acid transport happen?

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Figure 14.7: Glycocholate. Bile salts, such as glycocholate, facilitate lipid digestion in the intestine.

Lipids are prepared for digestion in the stomach. The grinding and mixing that takes place in the stomach converts lipids into an emulsion, a mixture of lipid droplets and water. Common emulsions include mayonnaise and shaken oil-and-vinegar salad dressing. After the lipids leave the stomach, emulsification is enhanced with the aid of bile salts, amphipathic molecules synthesized from cholesterol in the liver and secreted from the gall bladder in response to cholecystokinin (Figure 14.7). These molecules insert into the lipid droplets, making the triacylglycerols more readily digested. Triacylglycerols are degraded to free fatty acids and monoacylglycerol by enzymes secreted by the pancreas called lipases (Figure 14.8), which attach to the surface of a lipid droplet. Pancreatic lipases are also released into the intestine as zymogens that are subsequently activated. The final digestion products, free fatty acids and monoacylglycerol, are carried in micelles to the plasma membrane of the intestinal epithelial cells where they will subsequently be absorbed. Micelles are globular structures formed by small lipids in aqueous solutions (Figure 14.9). In a micelle, the polar head groups of the fatty acids and monoacylglycerol are in contact with the aqueous solution and the hydrocarbon chains are sequestered in the interior of the micelle. Micelle formation is also facilitated by bile salts. If the production of bile salts is inadequate due to liver disease, large amounts of fats (as much as 30 g per day) are excreted in the feces. This condition is referred to as steatorrhea, after stearic acid, a common fatty acid.

Figure 14.8: The action of pancreatic lipases. Lipases secreted by the pancreas convert triacylglycerols into fatty acids and monoacylglycerol for absorption into the intestine.
Figure 14.9: A diagram of a section of a micelle. Ionized fatty acids generated by the action of lipases readily form micelles.

The fatty acids and monoacylglycerol are transported into the intestinal cells by membrane proteins such as the fatty-acid-binding protein (FABP) (Figure 14.10). Once inside the cell, fatty-acid-transport proteins (FATP) ferry them to the cytoplasmic face of the smooth endoplasmic reticulum (SER), where the triacylglycerols are resynthesized from fatty acids and monoacylglycerol. After transport into the lumen of the SER, the triacylglycerols associate with specific proteins and a small amount of phospholipid and cholesterol to form lipoprotein transport particles called chylomicrons, stable particles approximately 2000 Å (200 nm) in diameter. These particles are composed of 98% triacylglycerols with the proteins and phospholipid on the surface. The chylomicrons are released into the lymph system and then into the blood (Chapter 29).

Figure 14.10: Chylomicron formation. Free fatty acids and monoacylglycerols are absorbed by intestinal epithelial cells. Triacylglycerols are resynthesized and packaged with other lipids and proteins to form chylomicrons, which are then released into the lymph system.

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!quickquiz! QUICK QUIZ

Explain why a person who has a trypsinogen deficiency will suffer from more digestion difficulties than will a person lacking most other zymogens.

After a meal rich in lipids, the blood appears milky because of the high content of chylomicrons. These particles bind to membrane-bound lipoprotein lipases, primarily at adipose tissue and muscle, where the triacylglycerols are once again degraded into free fatty acids and monoacylglycerol for transport into the tissue. The triacylglycerols are then resynthesized and stored. In the muscle and other tissues, they can be oxidized to provide energy, as will be discussed in Chapter 27. Chylomicrons also function in the transport of fat-soluble vitamins and cholesterol.

Figure 14.11: A rattlesnake poised to strike. Rattlesnakes inject digestive enzymes into their prospective meals.

!bio! BIOLOGICAL INSIGHT: Snake Venoms Digest from the Inside Out

Most animals ingest food and, in response to this ingestion, produce enzymes that digest the food. Many venomous snakes, on the other hand, do the opposite. They inject digestive enzymes into their prospective meals to begin the digestion process from the inside out, before they even consume the meals.

Snake venom, a highly modified form of saliva, consists of 50 to 60 different protein and peptide components that differ among species of snake and possibly even among individual snakes of the same species. Consider rattlesnakes (Figure 14.11). Rattlesnake venom contains a host of enzymes that digest the tissues of the victim. Phospholipases digest cell membranes at the site of the snakebite, causing a loss of cellular components. The phospholipases also disrupt the membranes of red blood cells, destroying them (a process called hemolysis). Collagenase digests the protein collagen, a major component of connective tissue, whereas hyaluronidase digests hyaluronidate, a glycosaminoglycan component of connective tissue. The combined action of both collagenase and hyaluronidase is to destroy tissue at the site of the bite, enabling the venom to spread more readily throughout the victim.

Various proteolytic enzymes in the venom degrade basement membranes (a thin sheet of fibrous proteins, including collagen, that underlies the epithelial cells) and components of the extracellular matrix, leading to severe tissue damage. Some venoms contain proteolytic enzymes that stimulate the formation of blood clots as well as enzymes that digest blood clots. The net effect of these enzymes acting in concert may be to deplete all clotting factors from the blood, and so clots do not form. Venoms also contain various peptides that have neurotoxic activities. The neurotoxins immobilize the prey, whereas the digestive enzymes reduce the size of the prey to make swallowing easier.

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Despite the toxic nature of snake venoms, and venoms of all sorts, the study of the components of deadly concoctions have yielded a virtual pharmacopeia of clinically useful drugs. Drugs to combat hypertension (high blood pressure) have been developed following studies of venom components of the South African pit viper Bothrops jararaca. Drugs that reduce the likelihood of myocardial infarction (heart attack) resulted from the examination of the venom of the Southeastern pigmy rattlesnake Sistrurus miliarius barbouri. A component of the venom from the copperhead Agkistrodon acutus is showing promise as an anticancer drug.