Digestion and Absorption: Carbohydrate, Lipid, Protein

Question 1

Amylose

Answer 1

• polysaccharide
• plant CHO
• storage linear chain with alpha 1,4 glycosidic bonds

Question 2

Amylopectin

Answer 2

• polysaccharide
• amylose + branches with alpha 1,6 glycosidic bonds

Question 3

Glycogen

Answer 3

• polysaccharide
• animal CHO storage
• similar to amylopectin except more branches

Question 4

Cellulose

Answer 4

• polysaccharide
• linear chain with beta 1, 4 glycosidic bonds

Question 5

Oligosaccharides

Answer 5

• 4-10 (avergage 8) glucose units
• alpha limit dextrin = branced (1 or 2 alpha 1,6 bonds)

Question 6

Early Digestion of Carbohydrates

Answer 6

• Initial hydrolysis begins with salivary (or lingual) alpha amylase
• The saliva also contains mucin, a glycoprotein that serves as a lubricant and helps disperse polysaccharides. Because this initial hydrolysis is quantitatively small, the predominant hydrolysis is catalyzed by pancreatic alpha-amylase, which is secreted in large excess, into the small intestine, relative to starch intake.

Question 7

Disaccharides and Moosaccharides

Answer 7

• Monosaccharides are carbohydrates containing at least three carbon atoms. The number of carbons is indicated by the prefix for the sugar such that hexoses contain six carbons and pentoses contain five carbons.
• glucose
• fructose
• sucrose
• lactose
• The state of the oxygen on the carbon in the 1-position determines whether a sugar can react with oxidized compounds (e.g., copper or iron).

-If the oxygen is not attached to some other structure, that sugar is a reducing sugar since the hydroxyl group (OH) on that carbon can donate electrons to reduce copper or iron. (lactose)

•Sucrose, a disaccharide of glucose and fructose, is non-reducing since the first carbon of the two sugar residues are joined leaving no free hydroxyl group to act as a reducing agent.

Question 8

Dietary Carbohydrates

Answer 8

• Dietary carbohydrates provide a major component of the daily caloric requirements accounting for >50% of calories in a typical US diet. Their complete oxidation to CO2 and H2O yields 4 cal/g. When there are insufficient amounts of carbohydrates in the diet, such as on a high protein diet, glucose is produced endogenously from amino acids or even galactose or fructose.
• Dietary polysaccharides are consumed mostly as starch, the storage form for carbohydrates in plants. Starch consists of either only linear chains of glucose molecules linked by alpha-1,4-glycosidic bonds (amylose) or of linear chains with occasional branch points created by the formation of alpha-1,6-glycosidic bonds (amylopectin).
• Glycogen, the principal animal polysaccharide, is similar in structure to amylopectin except that it has many more branch points. Glycogen, itself, is a minor dietary source of carbohydrates.
• Polysaccharides are hydrolyzed to mono-, di- and oligo saccharides by glucosidases, which are a special group of enzymes that hydrolyze glycosidic bonds. Cellulose, nondigestible carbohydrate (fiber), contains alpha-1,4-glycosidic bonds that cannot be hydrolyzed in mammalian intestine.

Question 9

Answer 9

•Since carbohydrates are absorbed as monosaccharides, the disaccharides (and oligosaccharides) must be processed further by glycosidase complexes that lie on the brush border surface of intestinal epithelial cells

Question 10

Polysaccharides

Answer 10

•Polysaccharides are polymers of monosaccharides held together by glycosidic bonds.

• Sucrose (table sugar) consists of one molecule each of glucose and fructose.
• Lactose (milk sugar) contains instead one molecule each of galactose and glucose. Maltose and trehalose each contain two molecules of glucose.

Question 11

Amylases

Answer 11

• Amylases, principally endosaccharidases, mostly cleave in the middle of the molecule, as opposed to exosaccharidases that remove terminal glucosyl units.
• Amylases are specific for alpha- 1,4-bonds in the linear chains of the molecule and do not attack branch points.
• The primary cleavage products from the action of amylase include: glucose, when only the terminal sugar is removed; maltose, a disaccharide of glucose; maltotriose, a trisaccharide of glucose; and oligosaccharides that on average contain eight glucosyl units. Oligosaccharides that contain one or two branches are alpha-limit dextrins.

Question 12

Answer 12

Question 13

Absorption of Monosaccharides

Answer 13

• The major monosaccharides resulting from carbohydrate digestion are glucose, galactose and fructose.
• Absorption of these and other minor monosaccharides are carrier-mediated processes that exhibit substrate specificity, stereospecificity and saturation kinetics.
• At least two types of monosaccharide transporters move monosaccharides from the intestinal lumen into the epithelial cell.

Question 14

GLUT - 5

Answer 14

• A Na+ -independent, facilitated diffusion type of monosaccharide transporter (GLUT-5) facilitates absorption primarily of fructose, but also some glucose.
• Xylose is also absorbed by GLUT-5. Because xylose is not metabolized in the body, its appearance in the blood serves as an indicator of successful monosaccharide absorption.
• Hexose sugars enter via the Na+ - independent transporter by virtue of the carbohydrate concentration gradient.

Question 15

SGLT - 1

Answer 15

• A Na+ -cotransporter (SGLT- 1) has high specificity for glucose and galactose and promotes “active” sugar absorption.
• The driving force for the Na+ -dependent transport is derived from the maintenance of low intracellular concentrations of Na+ by the action of the Na+ ,K+ -ATPase. Hydrolysis of ATP provides energy to export three Na+ ions in exchange for two K+ ions.
• The high gradient of Na+ between the intestinal lumen and the cytoplasm provides the driving force for active carbohydrate transport.

Question 16

GLUT - 2

Answer 16

• Intracellular carbohydrate concentrations are kept low by transport out of the cytoplasm to capillaries via Na+ -independent GLUT-2 transporter in the contraluminal plasma membrane.
• These monosaccharides then travel via the portal system to the liver where the bulk of these carbohydrates are metabolized.
• Some glucose also continues to other tissues for energy metabolism.

Question 17

Dietary Lipids

Answer 17

•On average, fat (lipid) comprises 37% of calories in the American diet.

Fat provides 9 cal/gm.

Dietary lipids are primarily (90%) triacylglycerols (TAGs; also referred to as triglycerides).

•The remainder includes cholesterol esters, phospholipids, essential unsaturated fatty acids and fat-soluble vitamins (A, D, E, K).

Question 18

Digestion of Dietary Lipids

Answer 18

• Normally, essentially all (98%) of the dietary fat is absorbed, and most is transported to adipose for storage.
• The poor water solubility of lipids presents problems for digestion because lipids are not easily accessible to the digestive enzymes in the aqueous phase, and lipolytic products tend to aggregate into larger complexes that make poor contact with the cell surface. This latter problem is overcome by “solubilization” of lipid products with amphipathic (i.e., containing both hydrophobic and hydrophilic portions) bile acids.
• Aside from the solubility aspects, the general principle of dietary lipid assimilation is that of hydrolyzing large non-absorbable molecules into smaller units.

Question 19

Six Steps of Lipid Digestion and Absorption

Answer 19

1. Minor Digestion
2. Major Digestion
3. Bile Acid
4. Passive Absorption
5. Reesterification
6. Assembly and Export

Question 20

Step 1: Minor Digestion

Answer 20

• TAGS in mouth and stomach by lingual (acid-stable) lipase
• triggers release of CCK in duodenum
• Digestion of lipids continues in the stomach catalyzed by an acid-stable gastric lipase, which is released from the gastric mucosa. Generally the rate of hydrolysis is slow because of solubility problems.
• However, some lipase can convert TAGs into fatty acids and DAGs at the water-lipid interface.
• The importance of this initial hydrolysis is that a fraction of the water-immiscible TAGs is converted to amphipathic products that cause dispersion of the lipid phase into smaller droplets (emulsification).
• This process provides more sites for association of enzyme molecules, both lingual/gastric lipase in the stomach, and eventually pancreatic lipase in the intestinal lumen.

Question 21

Step 2: Major Digestion

Answer 21

• all lipids in lumen of duodenum/jejunum; pancreatic lipolytic enzymes
• The entry of acid chyme and free fatty acids into the duodenal lumen stimulates endocrine cells to release cholecystokinin (CCK) into the bloodstream.
• CCK binds to its G-protein linked receptor on the gall bladder (CCK-A) causing contraction and hence release of bile salts into the intestinal lumen.
• CCK binding in human pancreas to G-protein linked CCK-B receptors causes secretion into the intestinal lumen of digestive (lipolytic) enzymes (e.g., trypsinogen).
• CCK also elicits the release of enteropeptidase into the lumen, where it activates trypsin from its zymogen form, trypsinogen.
• Other endocrine cells release secretin into the circulation. This hormone causes the pancreas to secrete bicarbonate-rich fluid that neutralizes the gut lumen pH for optimal enzymatic activity.
• These events are similar to that described for the effect of amino acids during protein digestion.
• The major enzyme for TAG hydrolysis is pancreatic lipase.

Question 22

Step 3: Bile Acid

Answer 22

• Bile acid facilitated formation of mixed micelles; present lipolytic products to mucosal surface, followed by enterohepatic bile acid recycling
• Bile Acids —> Bile Salts
• 75% end up recycled
• Bile acids can be considered as “biological detergents” that are synthesized exclusively in the liver from cholesterol, stored in the gallbladder as bile salts, and secreted into the duodenum to form micelles with the products of lipid digestion.
• Individuals who have bile duct obstruction absorb dietary lipids poorly, and instead eliminate them in the feces (steatorrhea).
• Shortly after a meal, bile salts/acids from the gallbladder and liver are released into the lumen of the upper small intestine.
• Bile acids act in the absorption of lipids by reversibly forming micelles, equilibrium structures with well-defined sizes that are much smaller than emulsion droplets. The arrangement of amphipathic bile acids in micelles is such that the hydrophobic portions (hydrocarbon rings) are removed from contact with water, while hydrophilic groups (hydroxyls and carboxylate) remain exposed to the water.
• Bile acids form micelles with other lipids, such as 2-monoacylglycerol, phospholipids, fatty acids, cholesterol and fat-soluble vitamins.
• These mixed micelles have disk-like shapes, wherein the phospholipids and fatty acids form a bilayer and the bile acids occupy the edge positions, rendering the edge of the disk hydrophilic.

Question 23

Step 4: Passive Absorption

Answer 23

• lipolytic products from mixed micelle into intestinal epithelial cell
• Uptake of lipids by the epithelial cells occurs in two ways: by passive diffusion through the apical membrane of duodenal and jejunal enterocytes of fatty acids and monoacylglycerols following micelle breakdown and by transport protein-mediated import of lipid.
• Absorption is virtually complete for fatty acids and 2-monoacylglycerols, which are slightly water-soluble. It is less efficient for water-insoluble lipids; for example, only 30% of dietary cholesterol is absorbed.
• After absorption of lipid digestion products, the micelles remain behind to solubilize other lipid products, thus acting as a type of “shuttle.”
• Bile acids are not absorbed at this point but instead travel the length of the small intestine and are absorbed in the terminal ileum by an ATP requiring active transport process.

Question 24

Step 5: Reesterification

Answer 24

• : 2-monoacylglycerol, lysolecithin, cholesterol with FFA inside intestinal enterocyte
• Within the intestinal cells, the fate of absorbed fatty acids depends on chain length.
• Fatty acids of medium chain length (6-12 carbon atoms) pass through the cell into the portal blood without modification.
• Long-chain fatty acids (>12 carbon atoms) become bound to a cytoplasmic intestinal fatty acid-binding protein (FABP) and are transported to the smooth endoplasmic reticulum where they are re-esterified into TAGs.
• Glycerol for this process is derived from the absorbed 2-monoacylglycerols.
• Cholesterol exists in the diet both as free cholesterol and as cholesterol ester.
• Prior to its absorption, cholesterol ester is hydrolyzed to free cholesterol by pancreatic esterase, and micellar solubilization is an obligatory step for its absorption.
• Before packaging into chylomicrons, cholesterol is re-esterified with fatty acid in the intestinal epithelial cell by acylCoA:cholesterol acyl transferase (ACAT).

•Lysophospholipids are also re-acylated with fatty acyl CoA to phospholipids, which form the surface of chylomicrons, a lipoprotein that transports in the circulation most lipids derived from the diet.

Question 25

Assembly and Export

Answer 25

• chylomicrons from intestinal cells to lymphatics; chylomicrons coated with Apo B48 (contain TAGs; CE; phospholipids)
• The resynthesized TAGs and cholesterol esters form lipid globules to which surface-active phospholipids and apolipoproteins adsorb to generate chylomicrons.
• Apolipoprotein association with resynthesized TAGs requires a transfer protein known as TAG transfer protein (TTP).
• The major intestinal apolipoprotein that coats the chylomicron is designated B48, which is essential for surface stabilization and chylomicron release from enterocytes.

-There is an analogous role of B100 for formation of VLDL (very low density lipoproteins).

•The nascent chylomicrons (lack apo CII and apo E) exit via the intestinal lymphatic vessels/lacteals to the thoracic duct after a lipid meal.

Question 26

Pancreatic Lipase

Answer 26

• The major enzyme for TAG hydrolysis is pancreatic lipase. Deficiency or inactivity of this enzyme leads to severe steatorrhea/diarrhea.
• Pancreatic lipase is specific for esters in the #1 and #3 carbon positions of glycerol and prefers to hydrolyze esterified long-chain fatty acids (>12 carbon atoms).
• The products are free fatty acids (FFA) and 2-monoacylglycerols (2MG).
• Pancreatic lipase is strongly inhibited by the bile acids that normally are present in the small intestine during lipid digestion. This problem of inhibition is overcome by colipase, a small protein that optimizes the activity of pancreatic lipase to efficiently hydrolyze dietary TAGs.

Question 27

Colipase

Answer 27

• Colipase binds to the bile-salt covered TAG interface. In this way, colipase facilitates the anchoring of pancreatic lipase to the water-lipid interface.
• By binding to the C-terminal end of the lipase, co-lipase stabilizes the enzyme in its most active conformation and thereby maximally directly activates it. In the pancreas, pancreatic lipase has extremely low activity in the absence of active colipase.
• The pancreas secretes colipase as the inactive procolipase that depends on tryptic removal of a portion for activity.
• Trypsinogen, a zymogen secreted by exocrine pancreas, is converted in the gut lumen to trypsin.
• Enteropeptidase catalyzes the cleavage reaction following release from intestinal cells stimulated by CCK

Question 28

Milk Lipase

Answer 28

• Milk lipase is functional in the neonatal intestine, and is especially important in the premature infant whose exocrine pancreas is not fully developed.
• Milk lipase, which is synthesized in the maternal mammary gland, is secreted in milk. Milk lipase survives the infant digestive tract. It is important to newborns for the digestion of milk fat, which is high in medium-chain TAG.
• Milk lipase hydrolyzes fatty acids from all three positions.
• In contrast to pancreatic lipase, the activity of milk lipase is enhanced by low concentrations of bile acids.

Question 29

Cholesterol Esterase

Answer 29

• Pancreatic juice also contains another less specific pancreatic esterase or cholesterol esterase, which acts on cholesterol esters, or other lipid esters such as esters of vitamin A.
• In contrast to pancreatic lipase, this pancreatic esterase is directly activated by bile acids.

Question 30

Phospholipase A2

Answer 30

• Daily dietary intake of phospholipids is low compared to TAG, but these lipids often contain essential unsaturated fatty acids.
• Phospholipids are hydrolyzed by specific phospholipases. Pancreatic secretions are especially rich in the proenzyme for phospholipase A2. As with other pancreatic proenzymes, this one is also activated by trypsin.
• Phospholipase A2 preferentially releases unsaturated fatty acids from the 2-position to yield lysophospholipids and free fatty acids.
• It requires both bile acids and calcium for activity.

Question 32

Micelles

Answer 32

• Micelles provide the major vehicle for moving lipids from the intestinal lumen to the cell surface where absorption occurs.
• Because the fluid layer next to the cell surface mixes poorly, the transport mechanism for solute flux across this “unstirred” fluid layer is diffusion down the concentration gradient.
• Bile acid micelles facilitate absorption by passive diffusion of the major dietary lipids, as well as free cholesterol and the lipid-soluble vitamins A, D, E, and K, by increasing their effective concentration in the unstirred layer.
• Thus, efficient lipid absorption absolutely depends on the presence of sufficient bile acids to “solubilize” the hydrolyzed ingested lipids in micelles and present them to the cell surface for absorption.

Question 33

Short and Medium Chain FA Path vs. Chylomicrons

Answer 33

•While dietary short- and medium-chain fatty acids reach the liver directly via the portal blood, the long-chain fatty acids bypass the liver by being released in the form of chylomicrons into the lymphatics. The bypass of the liver may have evolved to protect this organ from a lipid overload after a meal.

Question 34

The Fate of the Chylomicron

Answer 34

• The intestinal lymphatic vessels drain into the large body veins via the thoracic duct.
• Blood from the large veins first reaches the lungs and then the capillaries of the peripheral tissues, including adipose tissue and muscle, before it comes into contact with the liver.
• Adipose and muscle cells in particular take up and utilize large amounts of dietary fatty acids for storage and metabolism, respectively.
• On reaching the circulation, nascent chylomicrons acquire apoproteins CII, and E from HDL, creating the mature chylomicron.

-Apoproteins on HDL are made in intestinal cells, as well as in liver.

• The half-life of chylomicrons in the blood is about 5 to 20 minutes.
• TAGs in chylomicrons undergo lipolysis by lipoprotein lipase (LPL) to release fatty acids for adipose and muscle.
• LPL lies on the endothelial cell surface of capillary walls and hydrolyzes TAGs to release fatty acids taken up and used primarily by adipose and muscle cells.
• LPL is primarily associated with heart, skeletal muscle, adipose and mammary cells.
• In muscle, released fatty acids are oxidized for energy.
• In adipose cells, fatty acids are reesterified for storage as TAGs.
• LPL is activated by apolipoprotein CII, bound to phospholipids on the chylomicron (also VLDL in the endogenous lipid transport system).
• In the fed state, insulin increases activity of LPL while in starvation the activity declines.
• After repeated rounds of LPL action, apo CII is transferred from the shrinking chylomicron back to HDL.
• Chylomicrons decrease in surface area as the TAGs are progressively hydrolyzed until they are cholesterol ester-enriched chylomicron remnants.
• The remnants are taken up by the liver after binding to an apo E receptor. In this way, chylomicrons function to deliver fatty acids from dietary TAGs to muscle and adipose tissue, and dietary cholesterol plus fat-soluble vitamins to the liver.

Question 35

Lingual/Acid Stable Lipase

Answer 35

• mouth, stomach
• TAGs with medium chain FAs —> FFA +DAG
• Carbon cleaved: 3

Question 36

Pancreatic Lipase

Answer 36

• small intestine
• Regulated by colipase (+)
• TAGs with long chain FAs —> FFA + 2MG
• Carbon cleaved: 1 and 3

Question 37

Milk Lipase

Answer 37

• small intestine
• Regulated by: bile acids (+)
• TAGs with medium chain FAs —> FFA + glycerol
• Carbon clevaed: 1 and 2 and 3

Question 38

Phospholipase A₂

Answer 38

• small intestine
• Regulated by: bile acids (+), Ca2+ (+)
• PLs with unsaturated FA on position 2 —> Unsaturated FFA lysolecithin
• Carbon cleaved: 2

Question 39

Lipoprotein Lipase

Answer 39

• capillary walls
• Regulated by: APOCII (+), insulin (+)
• TAGs in chylomicron or VLDL –> FFA + glycerol
• Carbon cleaved: 1 and 2

Question 40

Hormone Sensitive Lipase

Answer 40

• adipose cell
• Rgulated by: insulin (-), glucagon (+), eppinephrine (+)
• TAG stored in adipose cells —> FFA + DAG
• Carbon cleaved: 3

Question 41

Digestion of Proteins

Answer 41

• To maintain tissue and organ functions, humans must ingest certain quantities of foodstuffs such as proteins, carbohydrates and lipids/fats.
• The bulk of ingested protein consists of large polypeptides that are not readily absorbed and, therefore, must be broken down to individual amino acids or short peptides (di or tri peptides) before they can be made available.
• Dietary proteins are cleaved by hydrolases with specificity for the peptide bond. These specific hydrolases are peptidases (also known as proteases).
• endopeptidases
• exopeptidases

Question 42

Endopeptidases

Answer 42

• attack internal bonds
• Endopeptidases are important for initially breaking down long polypeptides into smaller fragments, which then can be attacked more efficiently at either end by exopeptidases

Question 43

Exopeptidases

Answer 43

• cleave off one amino acid at a time from either the amino (NH3 + ) or the carboxyl (COO- ) terminus
• Exopeptidases can be further subdivided into amino- and carboxypeptidases, depending on which terminus they attack.

Question 44

Phases of Protein Digestion

Answer 44

1. Gastric Digestion
2. Pancreatic Proteases
3. Brush Border Surface
4. Absorption
5. Cleavage of Di and Tri peptides: Transport to Capillaries

Question 45

Phase 1: Gastric Digestion

Answer 45

• stomach
• stomach acid pepsin
• denaturation –> large peptide fragments and some free amino acids
• Stomach secretion (i.e., gastric juice) has a pH of about 1.0 because of the production of hydrochloric acid (HCl), which is secreted by the oxyntic (parietal) cells.
• This acidic environment causes proteins to denature making them more susceptible to proteolytic attack.
• Gastric juice contains proteases of the pepsin family. Pepsin is unique in that it is acid stable, and is active at acidic but not at neutral pH.
• Pepsin is secreted by the peptic (chief) cells of the stomach as the zymogen precursor, pepsinogen.
• Active pepsin is generated from pepsinogen by removal of amino acids from the N-terminus, either by intramolecular cleavage (autoactivation) below pH 5, or by autocatalytic cleavage of the zymogen by active pepsin.

•The major products of pepsin action on dietary protein are large peptide fragments and some free amino acids. Large peptide fractions enter the duodenum for further digestion.

Question 46

Phase 2: Digestion by Pancreatic Proteases

Answer 46

• lumen of small intestine
• trypsin, chymotrypsin, elastase, carboxypeptidases
• free amino acids, oligopeptides —> 2-8 amino acids
• Triggering events.
• Protein digestion is incomplete following action of pepsin. The small amounts of liberated amino acids that enter the duodenum are sufficient to trigger the release of cholecystokinin (CCK) from duodenal endocrine cells into the bloodstream.
• CCK initiates the secretion of protease zymogens from the acinar cells of the pancreas and stimulates the release of enteropeptidase into the gut.
• The pancreatic juice is rich in proenzymes of endopeptidases and carboxypeptidases (exopeptidases that cleave at the carboxy terminus).
• These proenzymes are activated only after reaching the lumen of the small intestine. Each peptidase is secreted as an inactive precursor to prevent spurious digestion and to provide a poised source of active peptidases that can be rapidly activated as food passes into the stomach and duodenum.

•Activation cascade.

• The key to activation of the pancreatic proenzymes is enteropeptidase (old name: enterokinase), a protease produced by duodenal epithelial cells.
• Trypsin initiates an amplified cascade of zymogen activation. Additionally, trypsin autocatalytically activates more trypsinogen to trypsin and acts on the other proenzymes, thus liberating chymotrypsin and elastase, from chymotrypsinogen and proelastase, respectively, and carboxypeptidases A and B, from their inactive procarboxypeptidase forms.

Question 47

Protease Characteristics

Answer 47

• Trypsin, chymotrypsin, and elastase are active only at neutral pH and therefore depend on NaHCO3 secreted by the pancreas for neutralization of gastric acid.
• Secretin, a hormone released into the blood from duodenal endocrine cells, stimulates the release of pancreatic fluid rich in bicarbonate.
• Once activated by neutralization of gastric acid, the three peptidases cleave on the carboxyl side of the amino acids for which they are specific though they differ considerably in their specificities.
• The combined action of these luminal peptidases on dietary protein results in the formation of free amino acids and small peptides of 2 to 8 residues, with peptides accounting for about 60% of the amino nitrogen at this point.
• Carboxypeptidase A and carboxypeptidase B exhibit additional specificities.
• They typically act on the di-, tri- and oligopeptide products of the three pancreatic endopeptidases.
• As exopeptidases, the products of their catalytic action are always free amino acids.

Question 48

Phase 3: Digestion at the brush Border Surface

Answer 48

• brush border surface
• endopeptidases, aminopeptidases
• free amino acides, di and tri peptides
• Since pancreatic juice does not contain appreciable aminopeptidase activity, final digestion of dipeptides and small oligopeptides depends upon duodenal and jejunal enzymes.
• The luminal surface (brush border) of intestinal epithelial cells is rich in peptidase activities.
• The end products of cell surface digestion are free amino acids, dipeptides and tripeptides.

Question 49

Phase 4: Absorption

Answer 49

• intestinal epithelial cell brush border
• five transport systems
• neutral (uncharged aliphatic and aromatic)
• basic (Cys-Cys)
• acidic (Asp, Glu)
• imino (Pro)
• di-/tri- peptides
• After digestion, amino acids and very small peptides are co-absorbed with sodium via groupspecific amino acid or peptide active transport systems in the apical membrane.
• The mechanism for concentrative transepithelial transport of L-amino acids is analogous to that for Na+ -dependent glucose absorption.
• The driving force for Na+ -dependent transport is derived from maintenance of low intracellular concentrations of Na+ by the action of the Na+ ,K+ -ATPase.
• Hydrolysis of ATP provides energy to export three Na+ ions in exchange for two K+ ions.
• Thus, the high gradient of Na+ between the intestinal lumen and the cytoplasm provides the driving force for active transport of amino acids.

•In contrast, the transporter for dipeptides and tripeptides involves a H+ -dependent co-transport that is driven indirectly by a Na+ -H+ exchange transport (not shown) , which establishes a H+ -gradient.

Question 50

Phase 5: Intracellular Cleavage by Dipeptidases and Tripeptidases Followed by Facilitated Diffusion Into the Capillaries

Answer 50

• epithelial cell - cytoplasm and contraluminal membrane
• dipeptidases and tripeptidases, facilitated diffsuin transporters
• free amino acids from dipeptidases and tripeptidases transported into capillaries
• Absorbed dipeptides and tripeptides are hydrolyzed by dipeptidases and tripeptidases within the cytoplasmic compartment before they leave the cell.
• For all practical purposes, only free amino acids are found in portal blood after a meal.
• Exit of amino acids at the contraluminal (basal-lateral) plasma membrane is Na+ -independent.
• The overall energy for concentrative amino acid absorption is derived directly from the electrochemical Na+ gradient and only indirectly from ATP.
• As with glucose absorption, the driving force is the “Na+ -vacuum” created within the intestinal cell by the Na+ ,K+ -ATPase.
• Absorption of dipeptides and tripeptides is indirectly driven by the Na+ -gradient by virtue of the Na+ -H+ exchanger.