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the result

of its escape from the inflamed exocrine cells of the pancreas into the surrounding pancreatic

veins. The cause of the inflammatory pancreatic process in this case was related to the toxic effect

of acute and chronic excessive alcohol ingestion.

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).

II. Absorption of Dietary LipidsThe 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. In patients such as Will S. who have severe and recurrent episodes of increased red blood

cell destruction (hemolytic anemia), greater than normal amounts of the red-cell pigment

heme must be processed by the liver and spleen. In these organs, heme (derived from hemoglobin)

is degraded to bilirubin, which is excreted by the liver in the bile.

If large quantities of bilirubin are presented to the liver as a consequence of acute hemolysis,

the capacity of the liver to conjugate it—that is, convert it to the water-soluble bilirubin

diglucuronide—can be overwhelmed. As a result, a greater percentage of the bilirubin entering the

hepatic biliary ducts in patients with hemolysis is in the less water-soluble forms. In the

gallbladder, these relatively insoluble particles tend to precipitate as gallstones that are rich in

calcium bilirubinate. In some patients, one or more stones may leave the gallbladder through the

cystic duct and enter the common bile duct. Most pass harmlessly into the small intestine and are

later excreted in the stool. Larger stones, however, may become entrapped in the lumen of the

cystic or common bile duct, where they cause varying degrees of obstruction to bile flow

(cholestasis) with associated ductal spasm, producing pain. If adequate amounts of bile salts do

not enter the intestinal lumen, dietary fats cannot readily be emulsified and digested.

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).Shortand medium-chain fatty acids (C4 to C12) do not require bile salts for their absorption. They

are absorbed directly into intestinal epithelial cells. Because they do not need to be packaged to increase

their solubility, they enter the portal blood (rather than the lymph) and are transported to the liver bound to

serum albumin.

When he was finally able to tolerate a full diet, Al M.’s stools became bulky, glistening,

yellow-brown, and foul-smelling. They floated on the surface of the toilet water. What

caused this problem?

Al M.’s stool changes are characteristic of steatorrhea (fat-laden stools caused by malabsorption of dietary fats), in this case caused by a lack of pancreatic secretions,

particularly pancreatic lipase, which normally digests dietary fat. Steatorrhea also may be caused

by insufficient production or secretion of bile salts. Therefore, Will S. might also develop this

condition.

III. Synthesis of Chylomicrons

Within the intestinal epithelial cells, the fatty acids and 2-monoacylglycerols are condensed by enzymatic

reactions in the smooth endoplasmic reticulum (ER) to form triacylglycerols. The fatty acids are activated

to fatty acyl coenzyme A (fatty acyl-CoA) by the same process used for activation of fatty acids before β-

oxidation (see Chapter 30). A fatty acyl-CoA then reacts with 2-monoacylglycerol to form diacylglycerol,

which reacts with another fatty acyl-CoA to form triacylglycerol (Fig. 29.6). The reactions for

triacylglycerol synthesis in intestinal cells differ from those in liver and adipose cells in that 2-

monoacylglycerol is an intermediate in triacylglycerol synthesis in intestinal cells, whereas phosphatidicacid is the necessary intermediate in other tissues. Triacylglycerols, owing to their insolubility in water, are packaged in lipoprotein particles. If

triacylglycerols entered the blood directly, they would coalesce, impeding blood flow. Intestinal cells

package triacylglycerols together with proteins and phospholipids in chylomicrons, which are lipoprotein

particles that do not readily coalesce in aqueous solutions (Fig. 29.7). Chylomicrons also contain

cholesterol and fat-soluble vitamins, but their major component is triglyceride derived from the diet (Fig.

29.8). The protein constituents of the lipoproteins are known as apolipoproteins.Because the fat-soluble vitamins (A, D, E, and K) are absorbed from micelles along with

the long-chain fatty acids and 2-monoacylglycerols, prolonged obstruction of the duct that

carries exocrine secretions from the pancreas and the gallbladder into the intestine (via the

common duct) could lead to a deficiency of these metabolically important substances. The major apolipoprotein associated with chylomicrons as they leave the intestinal cells is B-48. The

B-48 apolipoprotein is structurally and genetically related to the B-100 apolipoprotein synthesized in the

liver that serves as a major protein of another lipid carrier, very-low-density lipoprotein (VLDL). These

two apolipoproteins are encoded by the same gene. In the intestine, the primary transcript of this gene

undergoes RNA editing (Fig. 29.9, and see Chapter 15). A stop codon is generated that causes a protein to

be produced in the intestine that is 48% of the size of the protein produced in the liver; hence, the

designations B-48 and B-100.

The protein component of the lipoproteins is synthesized on the rough ER. Lipids, which are

synthesized in the smooth ER, are complexed with the proteins to form the chylomicrons.

Olestra is an artificial fat substitute designed to allow individuals to obtain the taste andfood consistency of fat without the calories from fat. The structure of Olestra is shown below and

consists of a sucrose molecule to which fatty acids are esterified to the hydroxyl groups.

The fatty acids attached to sucrose are resistant to hydrolysis by pancreatic lipase, so Olestra

passes through the intestine intact and is eliminated in the feces. As a result, no useful calories can

be obtained through the metabolism of Olestra, although in the mouth, the sucrose portion of the

molecule imparts a sweet taste. In addition, because Olestra has the ability to pass through the

digestive system unimpeded, it can also carry with it essential fat-soluble vitamins. Therefore,

foods prepared with Olestra are supplemented with these vitamins. Unfortunately, the side effects

of cramping and diarrhea decreased the popularity of Olestra as a food additive. IV. Transport of Dietary Lipids in the Blood

By the process of exocytosis, nascent chylomicrons are secreted by the intestinal epithelial cells into the

chyle of the lymphatic system and enter the blood through the thoracic duct. Nascent chylomicrons begin

to enter the blood within 1 to 2 hours after the start of a meal; as the meal is digested and absorbed, they

continue to enter the blood for many hours. Initially, the particles are called nascent (newborn)

chylomicrons. As they accept proteins from HDL within the lymph and the blood, they become “mature”

chylomicrons. HDLis the lipoprotein particle with the highest concentration of proteins, and lowest

concentration of triacylglycerol (see Chapter 32 for further discussion of HDLand other lipoprotein

particles found in the body).

Because of their high triacylglycerol content, chylomicrons are the least dense of the blood

lipoproteins. When blood is collected from patients with certain types of hyperlipoproteinemias (high concentrations of lipoproteins in the blood) in which chylomicron

levels are elevated, and the blood is allowed to stand in the refrigerator overnight, the

chylomicrons float to the top of the liquid and coalesce, forming a creamy layer. HDLtransfers proteins to the nascent chylomicrons, particularly apoE and apoCII (Fig. 29.10). ApoE

is recognized by membrane receptors, particularly those on the surface of liver cells, allowing apoEbearing lipoproteins to enter these cells by endocytosis for subsequent digestion by lysosomes. ApoCII

acts as an activator of LPL, the enzyme on capillary endothelial cells, primarily within muscle and

adipose tissue, that digests the triacylglycerols of the chylomicrons and VLDLin the blood.V. Fate of Chylomicrons

The triacylglycerols of the chylomicrons are digested by LPLattached to the

proteoglycans in the

basement membranes of endothelial cells that line the capillary walls (Fig. 29.11). LPLis produced by

adipose cells, muscle cells (particularly cardiac muscle), and cells of the lactating mammary gland. The

isozyme synthesized in adipose cells has a higher Km than the isozyme synthesized in muscle cells.

Therefore, adipose LPLis more active after a meal, when chylomicrons levels are elevated in the blood.

Insulin stimulates the synthesis and secretion of adipose LPL, so that after a meal, when triglyceride

levels increase in circulation, LPLhas been upregulated (through insulin release) to facilitate the

hydrolysis of fatty acids from the triglyceride.One manner in which individuals can lose weight is to inhibit the activity of pancreatic

lipase. This results in reduced fat digestion and absorption and a reduced caloric yield from

the diet. The drug orlistat is a chemically synthesized derivative of lipostatin, a natural lipase

inhibitor found in certain bacteria. The drug works in the intestinal lumen and forms a covalent

bond with the active-site serine residues of both gastric and pancreatic lipase, thereby inhibiting

their activities. Nondigested triglycerides are not absorbed by the intestine and are eliminated in

the feces. Under normal use of the drug, approximately 30% of dietary fat absorption is inhibited.

Because excessive nondigested fat in the intestines can lead to gastrointestinal distress related to

excessive intestinal gas formation, individuals who take this drug need to follow a diet with

reduced daily intake of fat, which should be evenly distributed among the meals of the day.

The fatty acids released from triacylglycerols by LPLare not very soluble in water. They become

soluble in blood by forming complexes with the protein albumin. The major fate of the fatty acids is

storage as triacylglycerol in adipose tissue. However, these fatty acids also may be oxidized for energy in

muscle and other tissues (see Fig. 29.11). The LPLin the capillaries of muscle cells has a lower Km than

adipose LPL. Thus, muscle cells can obtain fatty acids from blood lipoproteins whenever they are needed

for energy, even if the concentration of the lipoproteins is low.

The glycerol released from chylomicron triacylglycerols by LPLmay be used for triacylglycerol

synthesis in the liver in the fed state.

The portion of a chylomicron that remains in the blood after LPLaction is known as a chylomicron

remnant. The remnant has lost many of the apoCII molecules bound to the mature chylomicron, which

exposes apoE. This remnant binds to receptors on hepatocytes (the major cells of the liver), which

recognize apoE, and is taken up by the process of endocytosis. Lysosomes fuse with the endocytic

vesicles, and the chylomicron remnants are degraded by lysosomal enzymes. The products of lysosomal

digestion (e.g., fatty acids, amino acids, glycerol, cholesterol, phosphate) can be reused by the cell.

Heparin is a complex polysaccharide (a glycosaminoglycan) that is a component of proteoglycans (see Chapter 47). Isolated heparin is frequently used as an anticoagulant

because it binds to antithrombin III (ATIII), and the activated ATIII then binds factors necessary

for clotting and inhibits them from working. As LPLis bound to the capillary

endothelium through

binding to proteoglycans, heparin also can bind to LPLand dislodge it from the capillary wall.

This leads to loss of LPLactivity and an increase of triglyceride content in the blood.

CLINICAL COM M ENTS

Will S. The upper abdominal ultrasound study showed a large gallstone lodged in Will S.’s cystic

duct, with dilation of this duct proximal to the stone. Intravenous fluids were continued, he was not

allowed to take anything by mouth, antibiotics were started, and he was scheduled for a cholecystectomy.

Gallstones can also obstruct the common bile duct, which can cause bilirubin to flow back into the

venous blood draining from the liver. As a consequence, serum bilirubin levels, particularly the direct(conjugated) fraction, increase. Tissues such as the sclerae of the eye take up this pigment, which causes

them to become yellow (jaundiced, icteric). You can also see inflammation from a cystic duct obstruction

and cholecystitis causing some obstruction of the common bile duct and mild elevation of bilirubin.

Al M. Alcohol excess may produce proteinaceous plugs in the small pancreatic ducts, causing back

pressure injury and autodigestion of the pancreatic acini drained by these obstructed channels. This

process causes one form of acute pancreatitis. Al M. had an episode of acute alcohol-induced pancreatitis

superimposed on a more chronic alcohol-related inflammatory process in the pancreas—in other words,

chronic pancreatitis. As a result of decreased secretion of pancreatic lipase through the pancreatic ducts

and into the lumen of the small intestine, dietary fat was not absorbed at a normal rate, and steatorrhea

(fat-rich stools) occurred. If abstinence from alcohol does not allow adequate recovery of the enzymatic

secretory function of the pancreas, Mr. M. will have to take a commercial preparation of pancreatic

enzymes with meals that contain even minimal amounts of fat. BIOCHEM ICAL COM M ENTS

Microsomal Triglyceride Transfer Protein. The assembly of chylomicrons within the ER of the

enterocyte requires the activity of microsomal triglyceride transfer protein (MTP). The protein is

a dimer of two nonidentical subunits. The smaller subunit (57 kDa) is protein disulfide isomerase (PDI;

see Chapter 7, Section IX.A), whereas the larger subunit (97 kDa) contains the triglyceride transfer

activity. MTP accelerates the transport of triglycerides, cholesterol esters, and phospholipids across

membranes of subcellular organelles. The role of PDI in this complex is not known; the disulfide

isomerase activity of this subunit is not needed for triglyceride transport to occur. The lack of triglyceride

transfer activity leads to the disease abetalipoproteinemia. This disease affects both chylomicron

assembly in the intestine and VLDLassembly in the liver. Both particles require a B apolipoprotein for

their assembly (apoB-48 for chylomicrons, apoB-100 for VLDL), and MTP binds to the B apolipoproteins. For both chylomicron and VLDLassembly, a small apoB-containing particle is first

produced within the lumen of the ER. The appropriate apoB is made on the rough ER and is inserted into

the ER lumen during its synthesis (see Chapter 15, Section VIII). As the protein is being translated, lipid

(a small amount of triglyceride) begins to associate with the protein, and the lipid

association is catalyzed

by MTP. This leads to the generation of small apoB–containing particles; these particles are not formed in

patients with abetalipoproteinemia. Thus, it appears that MTP activity is necessary to transfer

triacylglycerol formed within the ER to the apoB protein. The second stage of particle assembly is the

fusion of the initial apoB particle with triacylglycerol droplets within the ER. The role of MTP in this

second step is still under investigation; it may be required for the transfer of triacylglycerol from the

cytoplasm to the lumen of the ER to form this lipid droplet. These steps are illustrated in Figure 29.12.The symptoms of abetalipoproteinemia include lipid malabsorption (and its accompanying symptoms

such as steatorrhea and vomiting), which can result in caloric deficiencies and weight loss. Because

lipid-soluble vitamin distribution occurs through chylomicron circulation, signs and symptoms of

deficiencies in the lipid-soluble vitamins may be seen in these patients.

MTP inhibitors have been investigated and studied for their effect on circulating lipid and cholesterol

levels. Although the inhibitors discovered to date are effective in lowering circulating lipid levels, they

also initiate severe hepatic steatosis (fatty liver), an unacceptable complication which could lead to liver

failure. The steatosis comes about by an accumulation of triglyceride in the liver owing to the inability to

form VLDLand export the triglyceride from the liver. The accumulation of triglyceride within hepatocytes

will eventually interfere with hepatic function and structure. Current research for MTP inhibitors is aimed

toward reducing the severity of fat accumulation in the liver (e.g., by specifically targeting the intestinal

MTP without affecting the hepatic MTP). KEY CONCEPTS

Triacylglycerols are the major fat source in the human diet.

Lipases (lingual lipase in the saliva and gastric lipase in the stomach) perform limited digestion of

triacylglycerol before food enters the intestine.

As food enters the intestine, cholecystokinin is released, which signals the gallbladder to release

bile acids and the exocrine pancreas to release digestive enzymes.

Within the intestine, bile salts emulsify fats, which increase their accessibility to pancreatic lipase

and colipase.

Triacylglycerols are degraded to form free fatty acids and 2-monoacylgylcerol by pancreatic lipase

and colipase.

Dietary phospholipids are hydrolyzed by pancreatic phospholipase A2 in the intestine.

Dietary cholesterol esters (cholesterol esterified to a fatty acid) are hydrolyzed by pancreatic

cholesterol esterase in the intestine.

Micelles, consisting of bile acids and the products of fat digestion, form within the intestinal lumen

and interact with the enterocyte membrane. Lipid-soluble components diffuse from the micelle into

the cell.

Bile salts are resorbed farther down the intestinal tract and are returned to the liver by the

enterohepatic circulation.

The intestinal epithelial cells resynthesize triacylglycerol and package them into nascent

chylomicrons for release into the circulation.Once they are in the circulation, the nascent chylomicrons interact with HDLparticles and acquire

two additional protein components, apoCII and apoE.

ApoCII activates LPLon capillary endothelium of muscle and adipose tissue, which digests the

triglycerides in the chylomicron. The fatty acids released from the chylomicron enter the muscle for

energy production or the fat cell for storage. The glycerol released is metabolized only in the liver.

As the chylomicron loses triglyceride, its density increases and it becomes a chylomicron remnant.

Chylomicron remnants are removed from circulation by the liver through specific binding of the

remnant to apoE receptors on the liver membrane.

Once it is in the liver, the remnant is degraded and the lipids are recycled. Table 29.1 summarizes the diseases discussed in this chapter.

REVIEW QUESTIONS—CHAPTER 29

1.Most of our dietary fats are incorporated into chylomicrons in the intestine. The most abundant

component of chylomicrons is which one of the following? A. ApoB-48

B. Triglyceride C. Phospholipid D. Cholesterol

E. Cholesterol ester

2.In order for the lipids in chylomicrons to be used by the tissues of the body, the nascent chylomicrons

need to be converted to mature chylomicrons. This conversion requires which one of the following?

A. Bile salts

B. 2-Monoacylglycerol C. LPL

D. HDL

E. Lymphatic system

3.Chylomicrons and VLDLcontain similar and different apolipoproteins. The apolipoproteins B-48and B-100 are similar with respect to which one of the following?

A. They are synthesized from the same gene.

B. They are derived by alternative spicing of the same heterogeneous nuclear RNA. C. ApoB-48 is a proteolytic product of apoB-100.

D. Both are found in mature chylomicrons. E. Both are found in VLDL.

4.Bile salts must reach a particular concentration within the intestinal lumen before they are effective

agents for lipid digestion. This is because of which one of the following?

A. The bile salt concentration must be equal to the triglyceride concentration. B. The bile salt solubility in the lumen is a critical factor.

C. The ability of bile salts to bind lipase is concentration-dependent.

D. The bile salts cannot be reabsorbed in the ileum until they reach a certain concentration.

E. The bile salts do not activate lipase until they reach a particular concentration.

5.Type III hyperlipidemia can be caused by a deficiency of apoE. Analysis of the serum of patients

with this disorder would exhibit which one of the following? A. An absence of chylomicrons after eating

B. Above-normal levels of VLDL after eating C. Normal triglyceride levels

D. Elevated triglyceride levels

E. Below-normal triglyceride levels

6.Pancreatitis can lead to a blockage of the pancreatic duct that, in turn, leads to steatorrhea. The

steatorrhea is most likely caused by the absence of which one of the following? A. Trypsin

B. Colipase C. Pepsin

D. Cholesterol esterase

E. Amylase

7.A patient has been taking an experimental drug to reduce weight. The drug leads to significant

steatorrhea and some night-blindness. A potential target of this drug is which one of the following?

A. LPL activity

B. Albumin synthesis C. Glucagon release D. Insulin release

E. Cholecystokinin release

8.A patient trying to lose weight is taking an over-the-counter “fat blocker” that supposedly blocks fat

absorption from the gastrointestinal tract. If this supplement truly blocked fat absorption, for which

vitamin below could the patient potentially develop a deficiency? A. K

B. B1 C. B3

D. B6E. C

9.The absence of which hormone listed would result in an inability to raise the pH of the partially

digested food leaving the stomach, leading to an inability to digest lipids in the intestine?

A. Pancreatic lipase

B. Intestinal cholecystokinin C. Pancreatic cholecystokinin D. Intestinal secretin

E. Pancreatic secretin

10.Shortand medium-chain fatty acids in the diet follow which one of the following digestive

sequences?

A. They are emulsified by bile acids. B. They are packaged in micelles.

C. They enter the portal blood after intestinal absorption. D. They enter the lymph after intestinal absorption.

E. They are formed by chylomicrons. ANSWERS TO REVIEW QUESTIONS

1.The answer is B. Chylomicrons transport dietary lipids, and >80% of the chylomicron is

triglyceride. All other components are present at <10%; hence, all other answers are incorrect.

2.The answer is D. HDLtransfers apolipoproteins CII and E to nascent chylomicrons to convert

them to mature chylomicrons. Bile salts are required to emulsify dietary lipid, 2-monacylglycerol

is a digestion product of pancreatic lipase, lipoprotein lipase digests triglyceride from mature

chylomicrons, and the lymphatic system delivers the nascent chylomicrons to the bloodstream.

3.The answer is A. Both apoB-48 and apoB-100 are derived from the same gene and from the same

messenger RNA (there is no difference in splicing between the two; thus, B is incorrect).

However, RNA editing introduces a stop codon in the message such that B48 stops protein

synthesis approximately 48% along the message. Thus, proteolytic cleavage is not correct. B48 is

found only in chylomicrons, and B100 is found only in VLDLparticles.

4.The answer is B. The bile salts must be above their CMC in order to form micelles with the

components of lipase digestion, fatty acids and 2-monoacylgycerol. In the absence of micelle

formation, lipid absorption would not occur. The CMC is independent of triglyceride concentration (thus, A is incorrect). Bile salts do not bind or activate lipase (thus, C and E are

incorrect). The absorption of bile salts in the ileum is not related to digestion (thus, D is

incorrect).

5. The answer is D. Nascent chylomicrons would be synthesized, which can only acquire apoCII

from HDL(thus, A is incorrect). The chylomicrons would be degraded in part by LPL, leading to

chylomicron remnant formation. However, the chylomicron remnants would remain in circulation

because of the lack of apoE (thus, B is incorrect). Because these remnant particles still contain a

fair amount of triglyceride, serum triglyceride levels will be elevated (thus, C and E are

incorrect).6. The answer is B. Lipase and colipase together are required to digest triglycerides from the diet.

Both are secreted by the exocrine pancreas through the pancreatic duct into the common duct and

then into the intestine. If colipase cannot make its way into the intestine, lipase is relatively

inactive, and triglyceride digestion will not occur. Thus, the triglycerides are eliminated via the

feces, leading to steatorrhea. The simultaneous reduction in other pancreatic exocrine secretions

leading to an inability to digest proteins (lack of trypsin; pepsin is found in the stomach), or

cholesterol esters (cholesterol esterase), or starch (amylase) does not lead to steatorrhea because

the triglycerides account for the majority of fat in the diet.

7.The answer is E. The patient, when taking the drug, is not digesting fat or absorbing fat-soluble

vitamins (the night-blindness is caused by a lack of vitamin A). This can occur because of

mutations in lipase or colipase, or an inability to release cholecystokinin. In the absence of

cholecystokinin, the digestive enzymes from the pancreas (including lipase and colipase) will not

be secreted to the intestine, nor will bile acids be secreted from the gallbladder to the intestine.

This would lead to inefficient triglyceride digestion and to loss of triglyceride and lipid-soluble

vitamins in the stools. Loss of LPL activity would lead to elevated triglyceride levels in the blood

but not the stool. Loss of albumin synthesis would lead to problems in blood volume but would

not lead to steatorrhea. Alterations in glucagon and insulin release do not affect triglyceride

digestion in the intestine.

8.The answer is A. Of those listed, only vitamin K is a fat-soluble vitamin, and the fat-soluble

vitamins are absorbed along with the lipids in the intestine. The other fat-soluble vitamins are D,

E, and A. Vitamin B1 is thiamin, B3 is niacin, and B6 is pyridoxamine. All of the B vitamins, and

vitamin C, are water-soluble, so their absorption into the intestinal epithelial cells would not be

blocked by this drug.

9.The answer is D. Intestinal cholecystokinin stimulates release of pancreatic lipase to digest

triglyceride, along with other enzymes to digest carbohydrates and proteins. Intestinal secretin

signals the liver, pancreas, and some intestinal cells to secrete bicarbonate. The pancreas does not

produce cholecystokinin or secretin.

10.The answer is C. Shortand medium-chain fatty acids do not require bile salts for their

absorption and therefore do not go into micelles or the lymph. They are absorbed directly into

intestinal epithelial cells and enter the portal blood, where they bind to serum albumin.Oxidation of Fatty Acids and Ketone

Bodies 30

For additional ancillary materials related to this chapter, please visit thePoint. Fatty acids are a major fuel for humans and supply our energy needs between meals and during periods of

increased demand, such as exercise. During overnight fasting, fatty acids become the major fuel for

cardiac muscle, skeletal muscle, and liver. The liver converts fatty acids to ketone bodies (acetoacetate

and β-hydroxybutyrate), which also serve as major fuels for tissues (e.g., the gut). The brain, which does

not have a significant capacity for fatty acid oxidation, can use ketone bodies as a fuel during prolonged

fasting.

The route of metabolism for a fatty acid depends somewhat on its chain length. Fatty acids are

generally classified as very-long-chain-length fatty acids (>C20), long-chain fatty acids (C12 to C20),

medium-chain fatty acids (C6 to C12), and short-chain fatty acids (C4).

ATP is generated from oxidation of fatty acids in the pathway of β-oxidation. Between meals and

during overnight fasting, long-chain fatty acids are released from adipose tissue triacylglycerols. They

circulate through blood bound to albumin (Fig. 30.1). In cells, they are converted to fatty acyl coenzyme

A (fatty acyl-CoA) derivatives by acyl-CoA synthetases. The activated acyl group is transported into

the mitochondrial matrix bound to carnitine, where fatty acyl-CoA is regenerated. In the pathway of β-

oxidation, the fatty acyl group is sequentially oxidized to yield reduced flavin adenine dinucleotide

(FAD[2H]), reduced nicotinamide adenine dinucleotide (NADH), and acetyl coenzyme A (acetyl-CoA).

Subsequent oxidation of NADH and FAD(2H) in the electron-transport chain, and oxidation of acetylCoA to CO2 in the tricarboxylic acid (TCA) cycle, generates adenosine triphosphate (ATP) from

oxidative phosphorylation.Many fatty acids have structures that require variations of this basic pattern. Long-chain fatty acids

that are unsaturated fatty acids generally require additional isomerization and oxidation–reduction

reactions to rearrange their double bonds during β-oxidation. Metabolism of water-soluble mediumchain-length fatty acids does not require carnitine and occurs only in the liver. Odd-chain-length fatty

acids undergo β-oxidation to the terminal three-carbon propionyl coenzyme A (propionyl-CoA), which

enters the TCA cycle as succinyl coenzyme A (succinyl-CoA).

Fatty acids that do not readily undergo mitochondrial β-oxidation are oxidized first by alternate routes

that convert them to more suitable substrates or to urinary excretion products. Excess fatty acids may

undergo microsomal ω-oxidation, which converts them to dicarboxylic acids that appear in urine. Verylong-chain fatty acids (both straight-chain and branched fatty acids such as phytanic acid) are whittled

down to size in peroxisomes. Peroxisomal α- and β-oxidation generates hydrogen peroxide (H2O2),

NADH, acetyl-CoA, or propionyl-CoA and a shortto medium-chain-length acyl-CoA. The acyl-CoA

products are transferred to mitochondria to complete their metabolism.

In the liver, much of the acetyl-CoA generated from fatty acid oxidation is converted to the ketone

bodies acetoacetate and β-hydroxybutyrate, which enter the blood (see Fig. 30.1). In other tissues,