Digestion and Absorption

Question 1

FUNCTIONS OF DIGESTION AND ABSORPTION

Answer 1

The main function of digestion is to hydrolyze large dietary components such as starch, proteins, and fats into their absorbable component parts (e.g., glucose, amino acids, fatty acids). Relatively small dietary substances such as the disaccharides lactose and sucrose are also hydrolyzed into their component simple sugars. In addition, digestion serves to release some vitamins, such as biotin and vitamin B12,
from their protein-bound forms.

including the stomach, liver, gallbladder, pancreas, small intestine, and colon, is
required for efficient digestion and absorption of the essential nutrients in foods.

The stomach produces hydrochloric acid, which denatures proteins, rendering them
more susceptible to proteolysis both by pepsin, produced by the stomach, and by
pancreas-derived proteases.

The liver produces and secretes bile salts, which are required for the digestion and absorption of triacylglycerols, which are comprised of long-chain fatty acids esterified to glycerol.

In addition to secreting numerous
digestive enzymes that act in the small intestine, ** the pancreas** secretes large amounts of sodium bicarbonate, which neutralize stomach acid, thus providing the nearly neutral pH required for the activity of pancreatic enzymes in the lumen of the small intestine.

The enterocytes that line the lumen of ** the small intestine **not only provide the surface to which disaccharidases and peptidases are attached, but are also the site where most of the small-molecular-mass products of digestion are absorbed.
The ileum is an integral element of the enterohepatic circulation that accounts for the recycling of bile salts and the absorption of essential nutrients such as vitamin B12. In addition, the small intestine is the body’s largest endocrine organ, as it produces a variety of hormones that regulate digestion and energy balance.

The colon is a major site of absorption of water and sodium and chloride ions. The colon is also the site of absorption of some of the metabolic by-products of colonic bacteria, particularly lactate, short-chain fatty acids such as propionate and butyrate, and ammonia, which is generated by hydrolysis of urea by bacterial urease.

Question 2

DIGESTION AND ABSORPTION OF CARBOHYDRATES

Answer 2

Dietary Carbohydrates
Digestion of Starch
Digestion of Oligosaccharides

Question 3

DIGESTION AND ABSORPTION OF CARBOHYDRATES
Dietary Carbohydrates

Answer 3

The major dietary carbohydrates are starch, sucrose, and lactose.

Starch, the polymeric form of glucose stored in plants, is a mixture of two macromolecular structures:
amylose and amylopectin (Fig. 3-1).

Amylose is a straight-chain polymer in which the glucose units are attached to one another through a-l,4 linkages. Amylopectin is a branched structure with branches formed by a- 1,6 glycosidic linkages to the a- 1,4 chains.

Animal foods contain small quantities of glycogen, a glucose polymer that is
similar to amylopectin but is more highly branched. Cellulose, the structural glucose polymer of plants, contains p-1,4 glycosidic bonds which are not hydrolyzed by human digestive enzymes. Cellulose is thus a dietary fiber rather than a bioavailable source of carbohydrate for the body.

Sucrose and lactose are disaccharides; that is, they are composed of two sugar units in glycosidic linkage (Fig. 3-2).

**Sucrose ** (table sugar), commonly extracted from sugarcane or sugar beets, consists of glucose (Glc) and fructose (Fru) and has the structure alpha-Glc(1 -> 2)beta-Fru.

Lactose is the sugar found in milk and is comprised of P-galactose linked to C4 of glucose [beta-Gal( 1 -> 4)GlcI.

Fructose and glucose are
also present as monosaccharides in honey and many fruits.
Most common monosaccharides and disaccharides are reducing sugars since they have a free aldehyde or ketone group. In an alkaline solution, a reducing sugar will reduce cupric ion (Cu2+) to cuprous ion (Cu+). By contrast, sucrose is not a reducing sugar.

Question 4

DIGESTION AND ABSORPTION OF CARBOHYDRATES
Dietary Carbohydrates
Digestion of Starch

Answer 4

Salivary and pancreatic amylases are both endoglycosidases that randomly hydrolyze internal alpha-1,4 glycosidic bonds of amylose and amylopectin to form smaller polysaccharides called dextrins.

Hydrolysis of the glucose polymers is initiated by salivary amylase (ptyalin), which hydrolyzes as much as 40% of dietary starch before the enzyme is inactivated by the low pH in the stomach.

Pancreatic a-amylase continues the starch digestion process in the small intestine, producing maltose [a-Glc(1-> 4)Glc], isomaltose [a-Glc( 1-> 6)Glc], and limit dextrins, which are a mixture
of oligosaccharides comprised of three to eight glucose units, including occasional
a- 1,6 branches

Question 5

DIGESTION AND ABSORPTION OF CARBOHYDRATES
Dietary Carbohydrates
Digestion of Oligosaccharides

Answer 5

The dietary disaccharides, sucrose and lactose, and the maltose, isomaltose, and
oligosaccharides produced by partial digestion of dietary starch are hydrolyzed by enzymes that are localized on the surface of the brush border of the intestinal mucosa.
Maltase
Isomaltase
Lactase
Sucrase
alpha-Dextrinase

Question 6

Dietary Carbohydrates
Digestion of Oligosaccharides
Maltase

Answer 6

Maltase is an alpha-glucosidase that hydrolyzes both maltose
(Fig. 3-3A) and maltotriose:

a-Glc( 1 -> 4)a-Glc( 1 –+ 4)Glc [maltotriose] + H20 -> maltose + glucose

a-Glc(1 -+ 4)Glc [maltose] + H20 -> 2 glucose

Question 7

Dietary Carbohydrates
Digestion of Oligosaccharides
Isomaltase.

Answer 7

Isomaltase is an alpha-glycosidase that hydrolyzes the alpha-1,6 glycosidic bond of isomaltose and limit dextrans (Fig. 3-3B):
alpha-Glc(1 -+ 6)Glc [isomaltose] + H20 -> 2 glucose

Question 8

Digestion of Starch
Digestion of Oligosaccharides
Lactase

Answer 8

Lactase is a beta-galactosidase that hydrolyzes lactose to glucose
and galactose (Fig. 3-2A):

beta-Gal(1 -+ 4)Glc [lactose] + H20 -> glucose + galactose

Question 9

Digestion of Starch
Digestion of Oligosaccharides
Sucrase.

Answer 9

Sucrase is a disaccharidase that hydrolyzes sucrose (Fig. 3-2B):

alpha-Glc(1 -> 2)beta-Fru[sucrose] + H2O -> glucose + fructose

It should be noted that the two polypeptides that have sucrase and isomaltase activity, respectively, are initially synthesized as a single polypeptide chain.

Question 10

Digestion of Starch
Digestion of Oligosaccharides
alpha-Dextrinase

Answer 10

This exoglycosidase hydrolyzes glucose alpha-1,4-glucose linkages starting at the nonreducing end of the oligosaccharide chain.
Although alpha-dextrinase has greater activity for oligosaccharides with relatively longer chains, it also hydrolyzes maltose and maltotriose.

Question 11

Absorption of Sugars
Glucose and Galactose

Answer 11

Glucose is absorbed into the cells of the
intestinal mucosa in cotransport with Na+ by GLUT1, the sodium glucose-dependent
symporter. This process is driven by the active transport of Na+ out of the cell
through the basolateral membrane, which also serves to maintain a low concentration of intracellular Na+.

Galactose binds to the glucose-binding site of GLUT1 and is transported into the mucosa by the same cotransporter. There is also a facilitative transport mechanism for glucose absorption.

Question 12

Absorption of Sugars
Fructose

Answer 12

Fructose is absorbed by facilitative diffusion, a process by which transport proteins facilitate the passage of a polar molecule across the plasma membrane.

Fructose transport is driven by the concentration gradient of fructose
across the membrane.

All of the common dietary monosaccharides leave the enterocyte through the basolateral membrane by means of facilitated diffusion.

Question 13

DIGESTION AND ABSORPTION OF DIETARY LIPIDS
Dietary Lipids

Answer 13

The major dietary lipids are triacylglycerols containing three long-chain fatty acids (usually C16-C20) esterified to glycerol (Fig. 3-4).

Animal products also contain both
free cholesterol and cholesteryl esters. Other dietary lipids include phospholipids,
vitamins A, D, E, and K, and the carotenoids.

Since lipids are hydrophobic and poorly soluble in water, they have a strong
tendency to aggregate into large lipid droplets. Efficient digestion of these droplets requires emulsification, the process by which large lipid droplets are dispersed into smaller ones, thus providing greater surface area for access by hydrolytic enzymes to their substrates.

The process of emulsification involves both the physical effects of peristaltic churning of the food and the chemical dispersion of the droplets by the
detergent action of bile salts.

Question 14

DIGESTION AND ABSORPTION OF DIETARY LIPIDS
Bile Acid and Bile Salts

Answer 14

Effective digestion and absorption of dietary lipids requires both digestive enzymes and conjugated bile acids (a.k.a. bile salts).

Bile acids are oxygenated derivatives
of cholesterol that have several hydroxyl groups on the sterol rings and a shortened hydrocarbon tail ending in a carboxyl group (Fig. 3-5). Bile acids are weak acids with a pK, value of about 6.

The term bile salts refers to conjugated bile acids which contain either glycine or taurine linked via an amide bond to the carboxyl group of a bile acid (Fig. 3-5C). Conjugation decreases the pK, of the bile salts; glycocholic acid has a pK, of about 4, whereas the pK, of taurocholic acid is about 2.

The stronger hydrophilic domains of the bile salts renders them more amphipathic than bile acids and thus more effective emulsifiers.

Question 15

Bile Acid and Bile Salts
Bile Salts Emulsify Dietary Lipids

Answer 15

The physical properties of the
bile salts enable them to emulsify lipid droplets, thereby enhancing lipid digestion.

Bile salts containing three hydroxyl groups (e.g., cholic acid) are better emulsifiers than those that have only two hydroxyl groups (e.g., deoxycholic acid).

Question 16

Bile Acid and Bile Salts
Bile Salts Stabilize Mixed Micelles

Answer 16

A second role that bile salts play
in the process of digestion and absorption of dietary lipids is the solubilization of the relatively hydrophobic products of lipid hydrolysis in the form of small aggregates called mixed micelles.

As shown in Figure 3-6, the stereochemistry of the hydroxyl
groups of the bile salts gives the planar ring structure a hydrophobic face and a
hydrophilic face. Mixed micelles have structures similar to small disks cut out of a membrane bilayer, with the bile salts stabilizing the cut edges.

Stabilization of mixed micelles by bile salts is required for the products of lipid hydrolysis to diffuse through the unstirred water layer near the surface of the intestine to the plasma membrane of the enterocyte brush border where they are absorbed.

Question 17

Hydrolysis of Dietary Lipids
Triacylglycerols

Answer 17

The enzymes that hydrolyze triacylglycerols (triglycerides) are called lipases.

The digestive lipases catalyze the partial hydrolysis of dietary fats containing long-chain fatty acids to a mixture consisting primarily of free fatty acids and 2-monoacylglycerols.

Several lipases contribute to triacylglycerol digestion, the major one being pancreatic lipase:

Catalysis by pancreatic lipases requires the presence of a second pancreatic product called colipase.

This 10-kDa nonenzyme protein reduces the surface tension at the lipid-aqueous interface, facilitating the interaction between the lipase and the lipid
droplet.

The body also produces lingual and gastric lipases. Although gastric lipase is
primarily active against substrates containing short-chain (C4-C6) and medium- chain (C8-C12) fatty acids, and is thus particularly important in the infant, it may also account for 10 to 30% of the hydrolysis of triacylglycerols, comprised of long-chain (C16-C20) fatty acids. The contribution of lingual lipase to fat digestion is normally quite low.

Interestingly, however, lingual lipase is not inactivated by the acid pH of the stomach and, in the absence of pancreatic secretion of bicarbonate, remains active in the small intestine as well. Thus, particularly in the absence of pancreatic lipase activity, lingual lipase can contribute significantly to the digestion of dietary triacylglycerols.

A neutral pH optimum, bile salt-stimulated lipase, present in human milk but not in cow’s milk, contributes substantially to triacylglycerol hydrolysis in the intestine of breast-fed infants.

Question 18

Hydrolysis of Dietary Lipids
Hydrolysis of Phospholipids

Answer 18

Pancreatic phospholipase A2 is secreted
as a zymogen (inactive proenzyme), which is activated by trypsin-catalyzed hydrol-
ysis. Phospholipase A2 catalyzes the partial hydrolysis of both dietary phospholipids and the phosphatidylcholine secreted by the liver and contained in the bile.

Pancreatic phospholipase A2 is specific for fatty acids in the 2-position of phospholipids but has a broad specificity with respect to both the phospholipid polar head groups and the chain length of the target fatty acid:

phosphatidylcholine + H20 -> 2-lysophosphatidylcholine + free fatty acid

Question 19

Hydrolysis of Cholesteryl Esters.

Answer 19

Dietary cholesterol is a mixture of
free cholesterol and cholesterol esterified with long-chain fatty acids. Pancreatic juice also contains a cholesterol esterase or cholesteryl ester hydrolase which catalyzes the following reaction:

cholesteryl ester + H20 -+ cholesterol + free fatty acid

Question 20

Absorption of Dietary Lipids and Chylomicron Formation

Answer 20

The products of lipid digestion include a mixture of partially hydrolyzed lipids
(primarily monoacylglycerols and lysophospholipids), free fatty acids, cholesterol, fat-soluble vitamins, and other lipophilic molecules (e.g., carotenoids).

All the products of lipid digestion ultimately become solubilized by bile salts to form small mixed micelles that diffuse from the lumen of the intestine toward the apical surface of the epithelium of the duodenum and jejunum, where the dietary lipids are absorbed.

Whereas absorbed glucose can readily be transported as such to the liver and other
tissues in the bloodstream, this process is not suitable for free fatty acids, because of both their limited solubility and their detergent properties, which could disrupt cell membranes and inhibit enzymes. Although free fatty acids released from adipocytes are transported in plasma bound to serum albumin, the higher concentrations of free fatty acids present after a meal would overwhelm this transport system.

Instead, the absorbed fatty acids are reesterified into less polar products for transport in the form of large lipoprotein aggregates called chylornicrons (Fig. 3-7).
The hydrophobic core of the chylomicrons consists primarily of triacylglycerol
molecules. It also contains cholesteryl esters and other absorbed lipophilic molecules, such as fat-soluble vitamins. The chylomicron particle is surrounded by a surface layer of phospholipids, free cholesterol, and proteins, primarily apoprotein B48 (apo B48) and apo Al.

After assembly, the chylomicrons are secreted from the enterocytes into
the lymphatic circulation, from whence they eventually enter the blood via the thoracic duct. The subsequent hydrolysis of the triacylglycerols of circulating chylomicrons is discussed in Chapter 12.

Resynthesis of Triacylglycerol
Reesterification of Other Absorbed Lipids
Absorption of Bile Acids
Digestion and Absorption of Triacylglycerols Containing Medium-Chain Fatty Acids

Question 21

Resynthesis of Triacylglycerol

Answer 21

In enterocytes, synthesis of triacyl-
glycerol occurs through the sequential action of monoacylglycerol acyltransferase
and diacylglycerol acyltransferase, for a net reaction

2-monoacylglycerol+ 2 fatty acyl-CoA -> triacylglycerol + 2CoASH

This pathway is distinct from the triacylglycerol synthesis pathway in other cells, such as hepatocytes and adipocytes, which utilizes glycerol 3-phosphate as the acceptor of acyl groups.

The conversion of free fatty acids to fatty acyl-CoA in enterocytes utilizes the ubiquitous fatty acyl-CoA synthetase reaction

fatty acid + ATP + CoASH -> acyl-CoA + AMP + PPi

Question 22

Absorption of Dietary Lipids and Chylomicron Formation
Absorption of Bile Acids

Answer 22

Bile salts are not absorbed together with
the products of hydrolysis of dietary triglycerides, phospholipids, and cholesteryl esters, and they are not incorporated into chylomicrons.

Instead, bile salts remain in the intestinal lumen until they reach the distal ileum (Fig. 3-8), where most are absorbed by an active transport mechanism that utilizes a Na+-bile salt cotransport system.

The bile salts are transported through the portal vein to the liver, where they
are extracted from the circulation by hepatocytes and then secreted back into bile.

Specific transporters on both ileal and hepatic cells are required for this process.

This enterohepatic circulation results in the secretion and reabsorption of the same pool of bile salts some 4 to 10 times a day, thus enabling the bile salts to be efficient promoters of fat digestion and absorption.

Those bile salts that are not reabsorbed in the ileum pass to the large intestine,
where they are deconjugated through the hydrolytic removal of glycine or taurine.
Bacterial metabolism also produces secondary bile acids, which have one less hydroxyl group than that of their respective primary bile acids. Some of these secondary bile acids are reabsorbed from the large intestine and returned to the liver, where they are reconjugated and reutilized. The remainder of the bile salts, approximately
0.8 glday, is excreted in the feces.

Question 23

Digestion and Absorption of Triacylglycerols Containing
Medium-Chain Fatty Acids.

Answer 23

The digestion and absorption of triacylglycerols containing short- and medium-chain fatty acids differs in several ways from that of the more common triacylglycerols that contain long-chain fatty acids.

First, additional lipases are available for the hydrolysis of the shorter-chain fatty acids. Gastric lipase preferentially hydrolyzes triacylglycerols in breast milk and some tropical oils (e.g., coconut) that contain large amounts of medium-chain fatty acids.

Nonhydrolyzed triacylglycerols containing medium-chain (C6-C12) fatty acids are also absorbed intact into cells of the intestinal mucosa, where they are hydrolyzed by a mucosal lipase.

Collectively, gastric- and mucosal-catalyzed lipolysis permits utilization of
medium-chain triglycerides as a dietary lipid in persons who produce insufficient
amounts of pancreatic lipase (e.g., patients with cystic fibrosis).

Medium-chain triacylglycerols, such as those in coconut oil and human milk, can also be digested and absorbed in the absence of bile salts, although the presence of bile salts does enhance
their absorption.

Since short- and medium-chain fatty acids are more soluble than C16 and C18
fatty acids, they can be transported as free fatty acids in the portal blood and are
not reesterified and incorporated into chylomicrons.

Thus, people with a reduced capacity for hydrolyzing triacylglycerols in circulating chylomicrons are sometimes prescribed diets in which triacylglycerols that contain medium-chain fatty acids are used in place of common dietary fats.

Question 24

DIGESTION AND ABSORPTION OF PROTEINS

Answer 24

1. Substrates for Protein Digestion
2. Enzymes That Contribute to Protein Digestion
3. Absorption of Components of Dietary Protein

Question 25

DIGESTION AND ABSORPTION OF PROTEINS
Substrates for Protein Digestion

Answer 25

The proteases of the digestive tract hydrolyze both exogenous or dietary proteins and endogenous proteins. Endogenous proteins include the proteases themselves as well
as the proteins derived from the lining of the gastrointestinal tract. In fact, the amino acids absorbed by an average person are derived almost equally from endogenous protein (70 glday) and dietary protein (60 to 90 glday).

Question 26

DIGESTION AND ABSORPTION OF PROTEINS
Enzymes That Contribute to Protein Digestion

Answer 26

1. Proteases
2. Carboxypeptidases
3. Aminopeptidases

Question 27

DIGESTION AND ABSORPTION OF PROTEINS
Enzymes That Contribute to Protein Digestion
1. Proteases

Answer 27

Proteases hydrolyze internal peptide bonds of polypeptides, producing smaller peptides and polypeptides (Fig. 3-9). The proteases involved in digestion are relatively specific for the amino acid side chain, designated R’ in Figure 3-9.

Pepsin, which is secreted by the stomach and active at acidic pH, is a relatively
nonspecific protease that recognizes the R group of many different amino acids,
including those that are dicarboxylic (Asp, Glu), aromatic (Phe, Tyr), or contain
large, bulky side groups (Leu, Met). Pepsin can digest as much as 10 to 20% of
the protein in a meal. Hydrolysis of dietary collagen by pepsin also facilitates the
subsequent access of pancreatic proteases to proteins in ingested meats.

The pancreas secretes several proteases, each with its own particular substrate
specificity. Trypsin cleaves peptide bonds on the C-terminal side of the basic amino
acids Arg and Lys, whereas chymotrypsin cleaves peptide bonds on the C-terminal
side of Leu, Met, Asn, and the aromatic amino acids Phe and Tyr. Elastase cleaves
on the C-terminal side of amino acids that have a small side chain, such as Ala, Gly,
and Ser.

Activation of Proteases. Pepsin is secreted in its zymogen form, pepsinogen, and
is then converted to the active protease by HC1. Once activated, pepsin can hydrolyze other molecules of pepsinogen to generate additional molecules of pepsin.

Pancreatic trypsinogen is activated by the hydrolytic action of enteropeptidase,
a protease that is synthesized by the brush-border cells of the small intestine. Once activated, trypsin can activate additional molecules of trypsinogen as well as other pancreatic enzymes:

trypsinogen + trypsin
chymotrypsinogen + chymotrypsin
proelastase + elastase

In all cases, activation of the proenzyme involves hydrolysis of one or more
peptide bonds, which results in the release of a segment of the polypeptide chain and permits the enzyme to assume a three-dimensional conformation that has a correctly configured active site.

Pancreatic Rypsin Inhibitor. The pancreas also secretes a small (6-kDa) protein
called pancreatic trypsin inhihitor that binds very tightly to the active site of trypsin.

Pancreatic trypsin inhibitor blocks the activity of any trypsin that may have resulted from premature conversion of trypsinogen to trypsin. This inhibitor thus acts to prevent a few active trypsin molecules from activating the full range of pancreatic digestive enzymes, which would otherwise damage the pancreas or pancreatic ducts.

Question 28

DIGESTION AND ABSORPTION OF PROTEINS
Enzymes That Contribute to Protein Digestion
2. Carboxypeptidases
3. Aminopeptidases

Answer 28

Carboxypeptidases

Pancreatic juice also contains carboxypeptidases A and B, which are zinc-dependent exopeptidases that cleave peptide bonds and release amino acids one at a time from the C-terminal end of peptides.

Both enzymes are secreted as zymogens and activated by trypsin.

Carboxypeptidase A is specific
for amino acids with hydrophobic side chains (e.g., valine, phenylalanine), whereas carboxypeptidase B is specific for basic amino acids (e.g., lysine, arginine).

Aminopeptidases.

Cells of the intestinal mucosa produce a number of intra- and extracellular aminopeptidases which release amino acids one at a time from the N-terminal end of peptide chains.

Question 29

DIGESTION AND ABSORPTION OF PROTEINS
Absorption of Components of Dietary Protein

Answer 29

Enterocytes of the small intestine absorb both amino acids and oligopeptides, par-
ticularly dipeptides and tripeptides. Indeed, oligopeptides may account for as much as two-thirds of the absorbed amino acids. There are numerous transport systems on the apical surface of the enterocyte for amino acids and peptides.

Many but not all of these transport systems require cotransport of sodium. Once inside the enterocytes, the peptides are hydrolyzed to free amino acids by intracellular aminopeptidases. Free
amino acids are then transported across the basolateral membrane and enter the blood.

Question 30

DIGESTION AND ABSORPTION OF MICRONUTRIENTS

Answer 30

**Fat-Soluble Vitamins **

Vitamins A (retinol), D (cholecalciferol), E (a-tocopherol), and K (phylloquinone
and menaquinone) are lipids with limited solubility in water. In the gastrointestinal
tract they are solubilized by bile salts, incorporated into mixed micelles along with the products of lipid digestion, and internalized by the intestinal mucosa.

Once inside the enterocytes, the fat-soluble vitamins are incorporated into chylomicrons for transport through the lymph into the blood and eventually to the liver. Thus, conditions that impair the digestion and absorption of dietary lipids, particularly the absence of bile salts, will also compromise the absorption of fat-soluble vitamins to an extent that
could lead to deficiencies of these vitamins.

p-Carotene and related retinoids are also lipids and require bile salts and mixed
micelle formation for absorption. Once inside the enterocyte, p-carotene is cleaved by 151 5’-carotene dioxygenase to two molecules of all-trans-retinal, which are then reduced by NADPH-dependent retinol dehydrogenase to all-trans-retinol and incorporated into chylomicrons for transport throughout the body (Fig. 3- 10).

**Absorption of Zinc and Copper Ions **
Levels of Zn2+ and Cu2+ in the body are regulated primarily by the extent of their
absorption from the gut. Digestion of proteins is required to release both of these divalent cations from protein-bound dietary sources.

Once inside the enterocytes, Zn2+ is initially bound to cysteine-rich intestinal
proteins (CRIPs), which serve as intracellular binding proteins for divalent cations.

Increased plasma concentrations of zinc lead to increased synthesis of thionein, a
low-molecular weight, cysteine-rich protein that binds zinc and other divalent cations.

The resulting Zn2+-thionein complex (metallothionein) sequesters Zn2 within the enterocyte and limits its transport across the basolateral membrane into the plasma.

At the end of their lifespan, enterocytes are sloughed, returning the Zn2+ to the lumen of the intestine, where it is eventually excreted in the feces. This process serves to prevent absorption of excess zinc by the body.

Thionein also binds absorbed Cu2+ ions and prevents excess absorption of copper.

Since zinc ions induce synthesis of thionein, excess dietary or pharmaceutical intakes of zinc increase the sequestration of copper ions within the enterocytes, which can lead to copper deficiency.

Question 31

REGULATION OF DIGESTION

Answer 31

The gastrointestinal (GI) tract is a major endocrine organ. The overall function of
the hormones secreted by the gut is to optimize digestion and absorption of nutrients from the gut by regulating GI motility and secretory processes. Following is a brief description of the role that some of these hormones play in digestion and absorption.

Gut Hormones

** Gastrin. **

Gastrin regulates HCI secretion by the stomach and has a growth promoting effect on the gastric mucosa. Histamine and acetylcholine also promote
HC1 secretion by ligand receptor-dependent mechanisms.

**Cholecystokinin (CCK). **

Cholecystokinin stimulates secretion of pancreatic enzymes as well as contraction of the gallbladder, which enhances bile flow. It is secreted by endocrine cells located mainly in the duodenum.

Secretin.

Secretin is a small polypeptide secreted by endocrine cells in the small intestine in response to a low pH (4). It stimulates secretion of pancreatic juice containing digestive enzymes and sodium bicarbonate, which neutralizes gastric
acid.

Question 32

ABNORMAL FUNCTIONING OF DIGESTION AND ABSORPTION

Answer 32

1. Lactase Deficiency
2. Celiac Disease
3. Gallstones
4. Steatorrhea
5. Hypergastrinemia
6. Parenterai Feeding

Question 33

ABNORMAL FUNCTIONING OF DIGESTION AND ABSORPTION
Lactase Deficiency

Answer 33

Lack of the enzyme lactase leads to lactose intolerance (i.e., development of diarrhea and gaseous abdominal distension following ingestion of lactose or milk sugar). Congenital lactase deficiency is a rare condition characterized by a total lack of
lactase activity.

More commonly, the inability of adults to tolerate lactose occurs due to lactase nonpersistence (a.k.a. lactose intolerance), in which a person is born producing sufficient lactase to digest milk sugar, but within the first decade of life gradually loses the ability to produce the enzyme.

Lactose nonpersistence is actually
the normal condition in humans and other mammals. Multiple occurrences of genetic mutations in the promoter region of the lactase gene enabled some members of cattle-raising populations in north-central Europe and sub-Saharan Africa to consume milk as well as meat. The mutations conveyed a powerful survival advantage and were thus subject to positive genetic selection.

Loss of lactase expression may also occur
secondary to disorders that damage the normal structure and function of the intestinal mucosa, such as acute diarrheal disease (e.g., enteritis), gastrointestinal parasites (e.g., giardiasis), enteropathies (e.g., celiac disease), and chronic inflammatory bowel disease (e.g., Crohn’s disease).

Question 34

ABNORMAL FUNCTIONING OF DIGESTION AND ABSORPTION
Celiac Disease

Answer 34

Celiac disease, also called celiac sprue, nontropical sprue, or ghiten-sensitive
enterpathy, is an autoimmune enteropathy characterized by intestinal inflammation and malabsorption following ingestion of gliadin, a component of a family of wheat proteins called glutens. In celiac disease there is villous atrophy (“flattening”), crypt hyperplasia, and accumulation of lymphocytes in the connective tissue immediately
under the intestinal epithelium.

Patients with celiac disease produce antibodies not only to gliadin but also to other proteins present in connective tissue surrounding smooth muscle cells in the intestinal wall. Loss of the intestinal villus and the enzymes associated with it deprives the gastrointestinal tract of important digestive enzymes (e.g., lactase). Impaired functioning of enterocytes also results in malabsorp-
tion of the products of digestion, especially amino acids, fatty acids, and fat-soluble vitamins, as well as minerals (e.g., copper, calcium). The disease can be treated with a gluten-free diet.

Question 35

ABNORMAL FUNCTIONING OF DIGESTION AND ABSORPTION
Gallstones

Answer 35

Gallstones are solids that form when crystals of cholesterol or bile pigments precipitate out of the liquid stored in the gallbladder. Stones that remain in the gallbladder and do not cause blockage are said to be silent. However, when the stones lodge in the ducts that carry bile from the liver to the small intestine, they can lead to inflammation of the ducts, the gallbladder, the pancreas, or the liver.

Gallstone attacks usually occur after high-fat meals but may also occur in the middle of the night. Acute inflammation can be extremely painful and chronic obstruction can lead to life-threatening pancreatic or liver disease.

Approximately 80% of gallstones are composed of cholesterol, which forms large yellow-green crystals or multiple tiny sandlike particles. They are most likely to
form when bile contains too much cholesterol or not enough bile salts, or when the gallbladder does not empty as rapidly as it should. The other 20% of gallstone cases result from formation of solid precipitates in which the major component is bilirubin, the breakdown product of hemoglobin, which gives the stool its dark color.

The most common treatment for both types of gallstones involves surgical removal of the gallbladder. Digestion of a fatty meal proceeds relatively normally even in the absence of a gallbladder, since bile flows out of the liver directly into the small intestine. Oral treatment with bile salts can dissolve small cholesterol stones, thereby obviating the need for surgery. Since bile salt therapy requires months of treatment and is often followed by reoccurrence of stones, it is reserved for persons for whom surgery is not an appropriate option.

Question 36

ABNORMAL FUNCTIONING OF DIGESTION AND ABSORPTION
Steatorrhea

Answer 36

Impaired functioning of any of the components of lipid digestion and absorption can result in steatorrhea or excretion of far in foul-smelling, bulky stools, and poor absorption of fat-soluble vitamins.

1. Impaired Hydrolysis of Triacylglycerol. Many conditions impair hydrolysis of dietary triacylglycerols. One of the most common of these conditions is
   chronic pancreatitis, which can result in decreased secretion of pancreatic lipase.
   Decreased intestinal activity of pancreatic lipase is also observed in patients with
   gastrinomas or other conditions that result in excess production of gastric HCI.

Steatorrhea is also a common side effect of the diet drug Xenical (orlistat), which inhibits pancreatic lipase activity.

2. Insufficient Secretion of Bile.

When blockage of the bile duct reduces
secretion of bile into the small intestine, the stools appear gray rather than reddish brown, reflecting the lack of excreted bile pigments. Lack of bile salts results in steatorrhea with excretion of free fatty acids rather than triacylglycerol in the stool.
This occurs because bile salts are required primarily for absorption of dietary fat and because significant hydrolysis of triacylglycerol by pancreatic lipase is possible even in the absence of bile salts. Bile salt insufficiency also results in impaired absorption of other dietary lipids, including the fat-soluble vitamins.

3. Impaired Absorption by the Intestinal Mucosa.

As indicated above, celiac disease or glutin-sensitive enteropathy results in malabsorption of dietary fat as well as other nutrients. Malabsorption of lipids may also occur as a result of mucosal inflammation, cystic fibrosis, bacterial overgrowth syndrome, and surgical resection of the small intestine.

Question 37

ABNORMAL FUNCTIONING OF DIGESTION AND ABSORPTION
Hypergastrinemia

Answer 37

Excessive secretion of gastrin (hypergastrinemia) is the cause of Zollinger-Ellison syndrome.

The hallmark of this syndrome is gastric and duodenal ulceration due to
excessive and unregulated secretion of gastric acid.

Hypergastrinemia can also be caused by gastrin-secreting tumors that develop in the pancreas or duodenum or by
infection with Helicohacter pylori, which induces mucosal inflammation.

Question 38

ABNORMAL FUNCTIONING OF DIGESTION AND ABSORPTION
Parenterai Feeding

Answer 38

There are many clinical conditions in which patients benefit from nutritional support which is parenteral, in that it completely bypasses the digestive system.

They include various severe malabsorptive syndromes, such as necrotizing colitis in infants, severe short bowel syndrome, and mechanical obstruction not immediately remediable by surgery.

Since nutrition is provided intravenously rather than via the digestive tract,
it is necessary to provide these patients with glucose rather than starch, and with
amino acids rather than protein.

By contrast, parenteral nutrition may include lipid emulsions (e.g., Intralipid, Liposyn) containing triacylglycerols stabilized by a surface layer of phospholipids. The lipid particles in these lipid emulsions are similar in size
to chylomicrons, and like chylomicrons, are hydrolyzed in the blood, releasing free
fatty acids and glycerol.

Parenteral nutrition solutions must also supply essential minerals and vitamins.