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Department of Biochemistry

Faculty of Medicine
Hasanuddin University

Biochemistry of
Digestive System

Ika Yustisia
August 2010

Contents
1. Introduction
2. General Principles of Digestion
3. Digestive enzymes
4. Digestion and Absorption of Carbohydrates
5. Digestion and Absorption of Lipids
6. Digestion and Absorption of Proteins
7. Clinical correlations
7.1. Lactose Intolerance
7.2. Malnultrition in Advanced Cancer and AIDS Patients
8. Conclusion

1. Introduction
Biochemistry is the study of the molecular events that correspond to
the phenomenon of life. One of the important phenomenon in the body is the
mechanism of digestion and absorption. Digestion is considered as the
degradation of the nutrient molecules into components simple enough to be
subsequently absorbed in the intestine. While absortion is the uptake of
digested

components

by

the

intestinal

cells

(enterocytes).

The

gastrointestinal (GI) tract with the organs functionally associated with it, are
responsible for the process of digestion and absorption.
Beside its association to the gastrointestinal tract in digestion and
absorption, liver has lots of function that plays a vital role in life of the
organism. It plays in intermediary metabolism, in the detoxification of foreign
toxic compounds including drugs, degradation of bilirubin, synthesis of
proteins, and as a strorage organ.
This hand out will be discussing about the biochemistry of the
digestive system especially about the digestive enzymes, epithelial transport,
and the digestion and absorption of the major nutrients. Some important
functions of the liver considered to be discussed in this handout, that have
not been studied in the other subjects/systems. Clinical correlations are given
in other to make a comprehensive understanding about the biochemistry of
the digestive system and the liver.
2. General Principles of Digestion
Considering to the definitions as mentioned above, the process of
digestion is characterized by several specific stages, which occur in
characteristic sequence, allowing the interaction of fluid, pH, emulsifying
agents, and enzymes. This requires concerted actions of the liver,
pancrease, gall bladder, and salivary glands. The process that are involved
can be summarized as follows1:
1. Lubrications and homogenizations of food with fluids secreted by glands
of the GI tract, starting in the mouth.

2. Secretion of enzymes whose prime function is the hydrolytic breakdown


of polymeric macromolecules to a mixture of oligomers, dimers, and
monomers.
3. Secretion of electrolytes, hydrogen ion, and bicarbonate within different
regions of the GI tract, to optimize the conditions for enzymes hydrolysis
specific to a particular region of the GI tract.
4. Secretion of the bile acids to emulsify dietary lipid, allowing appropriate
enzyme in hydrolysis and absorption.
5. Further hydrolysis within the jejunum by membrane-bound surface
enzymes.
6. Specific transport of digested material into enterocytes and thence to
blood or lymph.
To accomplish the processes above, the gastrointestinal tract contains
specialized glands and unique epithelial properties (table 1 and figure 1).
Table1. Major function of the gastrointestinal organs in digestion and absorption 1,2

Organ
Salivary glands
Stomach
Pancrease
Liver
Gallblader
Small intestine
Large intestine

Primary function
Production of fluid and digestive enzymes for
homogenization, lubrication, and digestion of
carbohydrate (amylase) and lipid (lingual lipase)
Secretion of HCl and proteases to initiate hydrolysis
of proteins
Secretion of HCO3-, proteases, lipases, and
amylase to continue digestion of protein, lipid, and
carbohydrate respectively
Elaboration of bile acids
Storage and concentration of bile
Final intraluminal digestion of foodstuffs, digestion
of carbohydrate dimers and specific absorptive
pathway for digested material
Absorption of fluid and electrolyte and products of
bacterial action in colon

There is considerable functional reserve in all aspect of digestion and


absorption. Minor functional loss may unnoticed by the individual, allowing
the pathology to progress for some time before being diagnosed. It means
that each of the organs involved in digestion and absorption has the capacity

to increase its activity several fold in response to specific stimulation. This


adds to the guts reserve capacity. For instance, maldigestion due to
pancreatic failure generally becomes a clinical problem only when the
pancreatic secretion rate of digestive enzymes drops to below one-tenth of
the normal rate. In addition, the gut can accommodate loss of function of one
particular organ. Both the pancrease and the small intestine can take over
after a total loss of gastric digestion, and lingual lipase can accommodate, in
part, some loss of pancreatic lipase production.1,2
3. Digestive Enzymes
Approximately 30 g of digestive enzymes are secreted per day. The
secretion of all these enzymes is similar in the salivary, gastric mucosa, and
pancrease. These organs contain specialized cell for synthesis, packaging,
and transport of the enzymes to the cell surface , and thence to the intestinal
lumen. These secretions are termed exocrine, that is secreting to the
outside.1,3
All digestive enzymes hydrolyze their substrates. The products of such
hydrolytic procedures are oligomers, dimers, and monomers of parent
macromolecules. Thus carbohydrates are hydrolyzed to a mixture of
disaccharides and monosaccharides. Proteins are broken down to a mixture
of di- and tripeptides and amino acids. Lipid, however, are treated differentlythey are broken down to a mixture of fatty acids, glycerol, and mono-, and
diacylglycerols.1
3.1. Salivary enzymes
The main function of saliva is not the digestion of nutrients but the
conversion of food into a homogeneous mass during mastication. The only
note-worthy enzymes in saliva are -amylase and lysozyme. Both are
endoglycosidases the cleave internal glycosidic bonds in a polyshaccaride
substrate. Exoglycosidases, in contrast, cleave glycosidic bonds at the ends. 3
-Amylase

cleaves

-1,4

glycosidic

bonds

in

starch

(further

explanation on Digestion and Absorption of Carbohydrates). It is active at

the normal salivary pH of 6.5 and 7.0 but is rapidly denatured in the acidic
environment of the stomach. Therefore, it makes only a minor contribution to
strach digestion. Its main function is to keep the teeth clean by dissolving
starchy bits of food that remain lodged between the teeth after a meal. 3
Lysozyme hydrolyzes -1,4 glycosidic bonds in the bacterial cell wall
polysaccharide peptidoglycan. Lysozyme kills some types of bacteria; others
are resistant because their peptidoglycan is protected from the enzyme by
other cell wall components or, in the case of the gram negative bacteria, by
an overlying outer membran. The members of the normal bacterial flora in
the mouth are also resistant to lysozyme. However, many bacteria from other
ecosystems are killed by lysozime while. 3
3.2. The stomach
In the stomach the food is mixed, stored for some time then finally
discharge into the duodenum. The stomach secretes enzymes, intrinsic
factor, and hydrochloride acid. The secretion of gastric juice is controlled by
neural mechanism involving the vagus nerve and by gastrin, the hormone of
the stomach.4
Gastrin is a polypeptide hormone produced and stored by the G cells
found in the antrum of the stomach and in the proximal duodenum. Gastrin
secretion is stimulated by the distension of the stomach, the presence of
proteins and polypeptide in the stomach, vagal stimulation, plasma calcium
concentration, and circulating catecholamines. Its secretion is inhibited by
acid in the antrum and by blood-borne factors such as secretin, gastric
inhibitory protein (GIP), vasoactive intestinal peptide (VIP), glucagon, and
calcitonin. Gastrin stimulates secretion of acid, pepsinogen (read the
zymogens), and intrinsic factor; increases gastric motility; and stimulates the
growth of gastric mucosa. Gastrin increases acid secretion and the acid then
feeds back to inhibit further gastrin secretion.

With a pH close to 2.0, the stomach is a forbidding place. This acidity


has three major fuctions: 1) kills most microorganism; 2) denatures dietary
proteins 3) requires for the action of pepsin. 3

Pepsin is considered to be the only important enzyme secreted by the


stomach. Pepsin is a protease with an unusually low pH optimum of 2.0. It is
considered an endopeptidases, but it also cleaves peptide bonds at the ends
of the polypeptide. Pepsin cleaves only some peptide bonds with a
preference for formed by amino groups of large hydrophobic amino acids.
Therefore, it produces a mix of oligopeptides along with some free amino
acids. This mix is known as peptone. Protein digestion has to be completed
by other enzymes in the small intestine.3
3.3. The pancrease secretions
In the acinar cells, the pancreas forms a secretion that is alkaline due
to its HCO3- content, the buffer capacity of which is sufficient to neutralize the
stomachs hydrochloric acid. The pancreatic secretion also contains many
enzymes that catalyze the hydrolysis of highmolecular-weight food
components. All of these enzymes are hydrolases with pH optimums in the
neutral or weakly alkaline range. Many of them are formed and secreted as
proenzymes and are only activated in the bowel lumen. 5
Trypsin, chymotrypsin, and elastase are endopeptidases that belong
to the group of serine proteinases. Trypsin hydrolyzes specific peptide bonds
on the C side of the basic amino acids Arg and Lys, while chymotrypsin
prefers peptide bonds of the apolar amino acids Tyr, Trp, Phe, and Leu.
Elastase mainly cleaves on the C side of the aliphatic amino acids Gly, Ala,
Val, and Ile. Smaller peptides are attacked by carboxypeptidases, which as
exopeptidases cleave individual amino acids from the Cterminal end of the
peptides. Carboxypeptidase A cleaves nonpolar amino acids from the
carboxyl end of peptides, and carboxypeptidase B cleaves basic amino
acids. Amylase, the most important endoglycosidase in the pancreas,
catalyzes the hydrolysis of 1 4 bonds in the polymeric carbohydrates
starch and glycogen. This releases maltose, maltotriose, and a mixture of
other oligosaccharides. Various pancreatic enzymes hydrolyze lipids,
including lipase with its auxiliary protein colipase, phospholipase A2, and

sterol esterase. Bile salts activate the lipid cleaving enzymes through micelle
formation.3,5
Several

hydrolasesparticularly

ribonuclease

(RNAse)

and

deoxyribonuclease (DNAse)break down the nucleic acids contained in


food.
3.4. Small intestine enzymes
The glands of the small intestine (the Lieberkhn and Brunner
glands) secrete additional digestive enzymes into the bowel.
Together with enzymes
on

the

microvilli

glycosidases,

etc.),

of

the

these

intestinal
enzymes

epithelium
ensure

(peptidases,

almost

complete

hydrolysis of the food components previously broken down by the


endoenzymes.5
The crypts of Lieberkuhn in the small intestine secrete
between 1 and 2 liters of a watery fluid every day, but this
secretion is almost devoid of digestive enzymes. There are,
however, enzymes attached to the luminal surface of the intestinal
mucosal cells. This surface, as known the brush border, measures
more then 200m because of the extensive folding of the villi and
the innumarable microvilli. The brush border enzymes are firmly
attached to the surface of the microvilli, with their catalytic
domains protruding into the intestinal lumen.3
There are a large number of different peptidases on brush
border membranes, including several types of aminopeptidas,
endopeptidases, carboxypeptidases, and dipeptidases that act on
the small oligopeptidases formed by pepsin and the pancreatic enzymes.
Nevertheless, a sizable portion of dietary protein is absorbed not in the form
of free amino acids but as dipeptides and tripeptides. These are further
hydrolyzed to free amino acids by cytoplasmic enzymes in the mucosal
cells.3

Disaccharidases and oligosaccharidases hydrolize sucrose and


lactose, as well as the maltose, maltotriose, and -limit dextrins that are
formed by the action of the -amylase on starch.3

3.5. Zymogens
Some digestive enzymes are potentially so damaging to the cells that
synthesizes them that they are secreted as inactive precursors or zymogens.
Among the digestive enzymes, the proteases and phospholipases are
dangerous. Once secreted, these zymogens are converted into their active
forms. This activation

process is irreversible. Trypsin, which is a major

protease involved in protein digestion in the duodenum, it is acted on by a


specialised peptidase, enteropeptidase, secreted by cells in the duodenal
wall. Enteropeptidase cleaves a peptide bond in trypsinogen, converting it to
trypsin. Trypsin, once formed, can act on further molecules of trypsinogen so
the activation process is autocatalytic. Trypsin also activates other protease
precursors from the pancrease, particularly chymotrypsinogen, proelastase,
and procarboxypeptidase. Pepsin, the major protease active in the stomach,
is secreted as its inactive precursor, pepsinogen. This is activated by an
autocatalytic process in the acid conditions of the stomach. 6
4. Digestion and Absorption of Carbohydrates
Dietary carbohydrates provide a major portion of the daily caloric
requirement. They consist of mono-, di-, and polysaccharides. The digestion
of carbohydrates is hydrolysis to liberate oligosaccharides, then free
monosaccharides (glucose, fructose, galactose) and disaccharides (sucrose,
maltose, lactose).2,4
Starch, a major nutrient, is a plant storage polysaccharides of over
100 kDa. It is a mixture of linear chains of glucose molecules linked by -1,4glucosidic bonds (amylose) and of branched chains with branch points of 1,6-glucosidic bonds (amylopectin). The ratio of branch points to -1,4glucosidic

bonds is

about

1:20.

Glycogen

is

the

animal

storage

polysaccharides and similar in structure to amylopectin, except that the


number of brach points is greater in glycogen. 2
Hydrated starch and glycogen are digested by the endosaccharides amylase of saliva and pancreatic juice. Hydration of the polysaccharides
occurs during heating and is essential for efficient digestion. Amylase is
specific for internal -1,4-glucosidic bonds; -1,6 bonds are not attacked nor
are -1,4 bonds of glucose units that serve as brach points. Pancreatic
amylase is secreted in large excess relative to starch intake and is more
importants for digestion than salivary enzyme. The products are mainly the
disaccharides maltose, the trisaccharides maltotriose, and so-called -limit
dextrins that contain on average eigth glucoseunits with one or more -1,6
glucosidic bonds.2
Final hydrolysis of di- and oligosaccharides to monosaccharides is
carried out by enzymes on the luminal surface of small intestinal epithelial
cells (brush border enzymes). They are disaccharidases, maltase, sucraseisomaltase, lactase, and trehalase. The products of these enzymes are free
monosaccharides (glucose, fructose, galactose) and disaccharides (sucrose,
maltose, lactose) that ready intestinal absorption. 2,4
There

are

two

separate

mechanisms

for the

absorption

of

monosaccharides in the small intestine. Glucose and galactose are absorbed


by a sodium-dependent process. They are carried by the same transport
protein (SGLT-1), and compete with each other for intestinal absorption.
Other monosaccharides are absorbed by carrier mediated diffusion. Because
they are not actively down their concentration gradient, and after a
moderately high intake, some may remain in the intestinal lumen, acting as a
substrate for bacterial fermentation.2,4

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Figure 1. Absorption of Carbohydrate 7


5. Digestion and Absorption of Lipids
An

adult

human

ingests

about

60-150g

of

lipid

per

day.

Triacylglycerols constitute more than 90% of this intake. The rest is made up
of phosphoslipids, cholesterol, cholesteryl ester, and free fatty acids. In
addition, 1-2g of cholesterol and 7-22g of phosphatidylcholine (lecithin) are
secreted each day by the liver and reach the small intestine with bile. 2
The poor water solubility of lipids presents problems for digestion
because substrates are not easily accessible to the digestive enzymes in the
aqueous phase. In addition, most products of lipid digestion are themselves
lipid with poor water solubility so that they tend to form aggregates that
hinder effectives absorption. These problems are overcome by (a)
generating/secreting surfactive molecules than increase the interfacial area
between aqueous and lipid phases and (b) solubilization of lipids with
detergents. Thus changes in the physical state of lipids are intimately
connected to chemical changes during digestion and absorption. 2
Hydrolysis of triacylglycerols is initiated by lingual and gastric lipases,
which attack the sn-3 ester bond forming 1,2 diacylglycerols and free fatty
acids, aiding emulsification. Pancreatic lipase is secreted into the small
intestine, and requires a further pancreatic protein, colipase, for activity. It is
specific for the primary ester links-ie, positions 1 and 3 in triacylglycerolsresulting 2-monoacylglycerols and free fatty acids as the major end products
of luminal triacylglycerol digestion. Monoacylglycerols are poor substrates for

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hydrolysis, so that less than 25% of ingested triacylglycerols is completely


hydrolyzed to glycerol and fatty acids. Bile salts, formed in the liver and
secreted in the bile, permit emulsification of the products of lipid digestion
into micelles together with phospholipids and cholesterol from the bile.
Because the micelles are soluble, they allow the products of digestion,
including the fat-soluble vitamins to be transported through the aqueous
environment of the intestinal lumen and permit dose close contact with the
brush border of the mucosal cells, allowing uptake into the epithelium. 4
Uptake of lipids by intestinal epithelial cells occurs by diffusion through
the plasma membrane. In addition, long chain fatty acids uptake is enhanced
by transporter (FATP4 or SLC27A4) and that of cholesterol uptake by
channel (Niemann-Pick C1-like protein) in the luminal membrane. 2
Within the absorbing epithelial cells, the fate of absorbed fatty acids
depends on chain length. Fatty acids of short and medium length ( 10
carbon atoms) pass into portal blood without modification. Long chain fatty
acids (> 12 carbon atoms) or their monoacylglycerols become bound to a
cytosolic fatty acid-binding protein (intestinal FAB or I-FABP) and are
transported to the endoplasmic reticulum, where they are converted into
triacylglycerols. Glycerol for this process is derived from the absorbed 2monoacylglycerols and, to a minor degree, from glucose. Cholesterol is
esterified

by

cholesterol

acyltransferase.

The

newly

synthesized

triacylglyserols and cholesteryl ester form lipids globules to which


phospholipids and apolipoproteins adsorb. The globules are called
chylomicrons because they can grow up to several micrometers in diameter
and leave the intestine through lymph vessels. Chylomicrons are synthesized
within the lumen of the endoplasmic reticulum whence they migrate through
the Golgi and then in vesicles to the contraluminal membrane. Interestingly,
chylomicrons do not enter the capillary space and the portal vein, instead
they travel through the intestinal lymph vessels and the thoracic duct to the
systemic venous system.2

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Figure 2. Absorption of Food Lipids7


While dietary medium-chain fatty acids reach the liver directly with the
portal blood, the long-chain fatty acids first reach adipose tissue and muscle
via the systemic circulation before coming into contact with the liver. Fat and
muscle cells take up large amounts of dietary lipids for storage or
metabolism. A bypass of the liver may have evolved to protect this organ
from lipid overload after meal.2
6. Digestion and Absorption of Proteins
The total daily protein load to be digested consist of about 70 100 g
of dietary proteins and 35 200 g of endogenous protein from digestive
enzymes and sloughed-off cells. Digestion and absorption of protein are very
efficient processes in healthy humans since about 1 -2 g of nitrogen are lost
through feces each day, which is equivalent to 6 -12 g of protein. 2
Protein are hydrolized by a whole range of peptidases, each with
specificity for peptide bonds between different amino acids. Few bonds are
accessible to the proteolytic enzymes, without prior denaturation of dietary
protein (by heat in cooking and by the action of gastric acid). Endopeptidases
(proteases) attack internal bonds and liberate large peptide fragment, while
exopeptidases cleave off one amino acids at a time from either the carboxyl
(carboxypeptidases)

or

the

amino

terminus

(aminopeptidases).

Endopeptidases are important for an initial breakdown of long polypeptides

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into smaller products, which can then be attacked more efficiently by


exopeptidases. The final products are free amino acids and di- and
tripeptides, which are absorbed by epithelial cells. 2
Free amino acids are absorbed across the intestinal mucosa by
sodium-dependent active transport. There are several different amino acids
transporter, with specificity for the nature different amino acids side-chain
(large or small, neutral, acidic, or basic). The various amino acids carried by
any one transporter compete with each other for absorption and tissue
uptake. Dipeptides and tripeptides enter the brush border of the intestinal
mucosal cells, where they are hydrolized to free amino acids, which are then
transported into the hepatic portal vein. Relatively large peptides may be
absorbed intact, either by uptake into mucosal epithelial cells (transcellular)
or by passing between epithelial cells (paracellilar). Many such peptides are
large enough to stimulate antibody formation this is the basis of allergic
reactions to foods.4

Figure 3. Absorption of Peptides and Amino Acids 7


7. Clinical correlations
7.1. Lactose Intolerance
Intestinal disaccharidase deficiencies are encoutered relatively
frequently in humans. Deficiency can be present in one or several enzymes

14

for a variety of reasons (genetic defect, physiological decline with age, or the
result of injuries to the mucosa). Lactase is the most commonly deficient
enzyme. Absolute or relative deficiency is experienced as milk intolerance. 2
Consequences of a lack of lactose hydrolysis in the upper small
intestine are inability to absorb lactose, which then becomes available for
bacterial fermentation in the lower small intestine. Bacterial fermentation
produces gas (distention of gut and flatulence) and osmotically active solute
that draw water into the intestinal lumen (diarrhea). Lactose in yogurt has
already been hydrolized during the fermentation process of making yogurt.
Thus, individuals with lactase deficiency can usually tolerate yogurt better
then unfemented dairy products.2
7.2. Malnultrition in Advanced Cancer and AIDS Patients
Patients with advanced cancer, HIV infection and AIDS, and a number
of other chronic disease are frequently undernourished, a condition called
cachexia. Physically, they show all the signs of marasmus, but there is
considerably more loss of body protein than occurs in starvation. The
secretion of cytokines in response to infection and cancer increases the
catabolism of tissue protein. This differ from marasmus, in which protein
synthesis

is

reduced,

but

catabolism

in

unaffected.

Patients

are

hypermetabolic, ie, a considerable increase in basal metabolic rate. Many


tumors metabolize glucose anaerobically to release lactate. This is then used
for gluconeogenesis in the liver, which is energy consuming with a net cost of
6 ATP for each mol of glucose cycled. There is increased stimulation of
uncoupling proteins by cytokines leading to thermogenesis and increased
oxidation of metabolic fuel. Futile cycling of lipids occurs because hormone
sensitive lipase is activated by a proteoglycan secreted by tumors resulting in
liberation

of

fatty

acids

from

adipose

tissue

and

ATP-expensive

reesterification to tryacylglycerols in the liver, which are exported in VLDL. 4


8. Conclusion
Digestion is degradation of the nutrient molecules into components
simple enough to be subsequently absorbed in the intestine. The major

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functional part of digestion is digestive enzymes. All digestive enzymes


hydrolyze their substrates. The products of such hydrolytic procedures are
oligomers, dimers, and monomers of parent macromolecules. Thus,
polysaccharides are hydrolyzed to a mixture of disaccharides and
monosaccharides, triacyglycerols as 2-monoacylglycerols, fatty acids, and
glycerol, and proteins as di- and tripeptides and amino acids. The products of
this enzymatic hydrolysis then are absorbed by intestinal mucosal cells with
different ways of absorption such sodium-dependent transport and carrier
mediated diffusion.

References:
1. Broom, I. Function

of the

Gastrointestinal Tract in

Medical

Biochemistry (Baynes, J.W., Dominiczack, M.H., editors), 2 nd ed.


Elsevier, 2005.
2. Hopfer, U. Digestion and Absorption of Basic Nutritional Constituents
in Textbook of Biochemistry with Clinical Correlations, Devlin, TM
(editor), 6th ed. Wiley Liss, 2006.
3. Meisenberg, G., Simmons, WH. Principles of Medical Biochemistry, 2
ed. Mosby Elsevier, 2006.
4. Bender, D.A., Mayes, P.A. Nutrition, Digestion, and Absorption in
Harpers Ilustrated Biochemistry, Murray, RK., Granner, DK., Rodwell,
VW(editors), 27th ed., 2006
5. Koolman, J.; Roehm, KH. Color Atlas of Biochemistry, 2 ed. Thieme,
2005.
6. Brownie, A.C., Kernohan, J.C. Biochemistry A Core Text with Selfassessment. Churchill Livingstone, 2000.

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