DIGESTION AND ABSORPTION

By Dr. Chris McIntosh and Dr. Cal Roskelley (roskelly@mail.ubc.ca)

INTRODUCTION

Lumen
Glycocalyx (Fuzzy
Coat)

Unstirred Layer

Water, ions and vitamins are absorbed directly by

the intestine without further modification. However
proteins, lipids and carbohydrates must first be
digested prior to absorption. There are four regions
that provide the enzymes responsible for digestion:
the salivary glands, stomach, pancreas and small
intestine (Fig. 1).

Microvillus
Tight
Junction
Intercellular
Space
Basement
Membrane
Capillary or
Lymph vessel

Amylase

Pepsin
Lipase
Enteropeptidase
Lactase
Maltase-Glucoamylase
Isomaltase-Sucrase
Trehalase
Aminopeptidase
Dipeptidyl Peptidases
Alkaline Phosphatase

Amylase
Trypsin
Chymotrypsin
Carboxypeptidase
Elastase
Lipase-Colipase
Phospholipase A2
Cholesterolesterase

Figure 2. Major Barriers Restricting

Absorption from the Intestinal Lumen to the
Blood or Lymph

ENTEROCYTE TRANSPORT
PATHWAYS

Bacterial
Enzymes

There are two routes by which molecules can pass

from the lumen into the bloodstream or lymphatics:
between cells, the paracellular route, or across the
cell plasma membranes, the transcellular route.

Figure 1. Sources of Digestive Enzymes

Following digestion, absorption takes place through
the mucosa. Although the plasma membrane of the
enterocyte is the main factor that restrains free
movement of substances from the lumen into the
blood or lymph, transmural movement involves a
number of barriers (Fig. 2):
1.
2.
3.
4.
5.
6.
7.
8.

Unstirred layer of fluid

Glycocalyx ("fuzzy coat") covering
microvilli
Cell membrane
Cytoplasm of the enterocyte
Basal or lateral cell membrane
Intercellular space
Basement membrane
Wall of the capillary or lymph vessel

A. Paracellular Transport
The paracellular route involves passage of molecules
through
tight
junctions
in
response
to
electrochemical, osmotic and hydrostatic pressure
gradients.
Lipid
Bilayer

Water-Permeable Carrier Protein or

Pores
Ion Channel

Carrier
Protein

the

Electrochemical
Gradient

Energy
Passive
Diffusion

Facilitated
Diffusion

Active
Transport

Figure 3. Transcellular Transport Pathways

B. Transcellular Transport
Transcellular transport involves several different
mechanisms (Fig. 3).

Specific uptake systems for sugars, amino acids,

peptides and bile salts have been characterized. Many
of these uptake systems are coupled to the Na+ pump
(secondary active transport).

i. Passive Diffusion

iv. Micropinocytosis

The driving force for passive diffusion across the

epithelial membrane is the electrochemical gradient.
Lipid soluble molecules, including some drugs and
fat-soluble vitamins, rapidly cross the membrane.
The mucosa acts as a barrier to water and water
soluble (polar) substances.

Uptake of large molecules by formation of a

pinocytic vacuole occurs at the base of the microvilli.
It is an important pathway in the uptake of protein
and lipids.

ii. Facilitated Diffusion

Absorption of nutrients begins in the duodenum and

is usually complete in the upper 30-50% of the small
intestine. Some ions, (calcium, magnesium, sodium)
and water soluble vitamins are absorbed throughout
the small intestine (Fig. 4). Absorption of fat is more
delayed than carbohydrate absorption because
digestion is more complex. Vitamin B12 and bile
salts
are
absorbed
in
the
ileum.

Transport by a membrane carrier or ion channel not

associated with metabolic energy expenditure (See
Fructose absorption).

iii. Active Transport

SITES OF ABSORPTION

Figure 4. Sites of Absorption in the Gastrointestinal Tract

LIPID DIGESTION AND ABSORPTION

Fat comprises ~40% of North American dietary
calories. Triglycerides (TG) are the major constituent
of dietary fat. Other lipids are cholesterol,
phospholipids (mainly lecithin) and fat soluble
vitamins. Animal fats contain saturated (mostly
palmitic, C16 and stearic, C18) and unsaturated (oleic
and linoleic, C18) fatty acids. In a healthy individual
fat absorption is ~98% efficient.
Digestion and absorption of lipids is complex due to
insolubility of most fats in water. The stages leading
to entry of fat into the bloodstream include (Fig. 5):
A.
B.
C.
D.
E.
F.

Emulsification
Hydrolysis
Micellar Solubilization
Absorption
Re-synthesis of triglycerides and phospholipids
Absorption of lipids into the blood and lymph,
and their subsequent transport

Gastric Lipase
1.
2.

3.

Present early in neonatal development.

Has a broad pH optimum (2-6) and a preference
for the long chain fatty acid in the 3-position of
tryglycerides (Fig. 6). The products are mainly
diglycerides and fatty acids.
Can account for the major part of total GI
lipolytic activity in cystic fibrosis.
Triglyceride!

1,2-Diglyceride!

GASTRIC!
LIPASE!

Fatty Acid!

Figure 6. Hydrolysis of Triglyceride

by Gastric Lipase
Trituration and mixing in the distal stomach break
lipids up into small droplets, thus forming an
emulsion (see below) containing small lipid particles.
Fatty acid products of lipolysis help in emulsification
(Fig. 7).
Acid Lipase
Fatty
Acids

Mechanical
Mixing

Figure 7.
Fatty Acids Produced During
Gastric Lipolysis Help Emulsification in the
Stomach

Figure 5 . Outline of the Events Involved in

the Digestion and Absorption of Fats
Intragastric Lipid Digestion
Fat digestion begins in the stomach with gastric
lipase, and this accounts for 10-30% of total fat
digestion.

Gastric emptying is slowed by the presence of fat in

the duodenum (enterogastrone and the enterogastric
reflex). This ensures that the maximum capacity for
duodenal digestion and absorption of fat are not
exceeded.

Emulsification
1.
2.

Emulsification is the formation of a dispersion

(emulsion) of immiscible liquids (fat and water).
The main emulsifying agents are the dietary
proteins and fatty acids in the stomach, and fatty

3.

acids, monoglycerides, lecithin, lysolethicin,

proteins and bile salts in the duodenum (Fig. 8).
Emulsification produces droplets with a diameter
of 0.5 to 1 m and a surface area increased
several thousand-fold. The lipolytic enzymes
therefore have a larger surface area on which to
bind.

Intestinal Hydrolysis of Fats

The majority of fat appears in the duodenum
undigested. Bicarbonate, secreted by both the
duodenum and the exocrine pancreas, neutralizes acid
entering from the stomach. Bile, released from the
gallbladder, and pancreatic enzymes are also secreted
into the proximal duodenum.
There are three classes of pancreatic enzymes
involved in intestinal fat digestion:

LYSOLECITHIN!

1.

BILE SALTS!

P!

+!

FATTY ACIDS!

2.
PROTEIN!
Droplet!
P!

+!

LECITHIN!

Diameter!
0.5-1 m!

EMULSION!

Figure 8. Emulsification of Fats

3.

Pancreatic lipase (glycerolester hydrolase)

preferentially cleaves fatty acids from the 1 and
3 positions of triglycerides, yielding fatty acids +
2-monoclycerides (Fig. 9).
Cholesterolesterase cleaves ester bonds in
cholesterol esters to yield fatty acids +
cholesterol.
Phospholipase A2 converts phospholipids
(lecithin) to fatty acids and lysolecithin. This
enzyme is secreted in an inactive form, and is
2+
activated by Ca .

Figure 9. Fat Hydrolysis

For pancreatic lipase to act it must be spread

over the surface of the fat droplet. These droplets
become coated with bile salts. Bile salts clear the

lipid emulsion from adsorbed protein, but they

also inhibit binding of the lipase. Procolipase is
secreted from the pancreas in equimolar amounts

to pancreatic lipase and is activated by trypsin in

the intestine. The lipase-colipase complex binds
to the bile salt-coated fat droplets. Binding is
enhanced by fatty acids released during lipolysis.
(Note: Cholesterolesterase is also known as
bile-salt activated lipase and it can also convert
triglycerides to glycerol and fatty acids; a similar
enzyme is present in milk).

Micellar Solubilization
In the absence of bile salts the products of lipolysis
(fatty acids and monoglycerides) form layered
(lamellar) products (Fig. 10). In the presence of bile
salts these are readily solubilized into micelles:
macromolecular aggregates of bile salt molecules that
bring other insoluble lipid materials into solution.

2.

Micelles diffuse through the "unstirred water

layer" at the surface of enterocytes. Lipolytic
products, but not bile acids, cross the enterocyte
membranes.

Lipid Absorption
Most lipid absorption takes place in the jejunum and
proximal ileum. Absorption of products of lipolysis
into the enterocyte is dependent upon the size and
lipid solubility of the molecule.
1.

Short and medium chain fatty acids (C4-C10) pass

into cells without micellar solubilization. They
may partition freely into the membrane and then
enter the cell (Fig. 12). However brush border
membrane fatty acid binding proteins probably
facilitate transport across the membrane.

Figure 10. Bile Salts Disperse the Products of

Fat Hydrolysis

Figure 12. Mechanisms

Transport of Fatty Acids

Important characteristics of micelles include:

1. Fatty acids and 2-monoglycerides dissolve in the
micelle and so gain aqueous solubility (Fig. 11).
This process is known as micellar solubilization.
Poorly soluble fats dissolve in the core of
micelles. These include long chain fatty acids
(>12C), 2-monoglycerides, lecithin, fat-soluble
vitamins and cholesterol.

2.

3.

4.
5.
6.

of

Membrane

Micelles diffuse through the "unstirred water

layer". Micelles are quasi-stable structures and
break down at the moment of absorption.
Spontaneous dissociation of long chain fatty
acids and monoglycerides from the micelles
allows them to enter the cell (Fig. 13). Fatty
acid-binding proteins in the microvillus
membrane may again be involved in transporting
fatty acids; monoglyceride transport is passive.
Cholesterol also dissociates from micelles.
Absorption may involve a binding protein
Bile salts can reform micelles or are absorbed
and enter the enterohepatic circulation.
Unchanged triglyceride may be absorbed by
pinocytosis but this is an insignificant pathway.

Resynthesis of Tryglycerides and

Absorption of Lipids into the
Blood and Lymph
Figure 11. Bile Salts Solubilize Products
of Lipolysis in Mixed Micelles

1.

Most medium and short chain fatty acids enter

the portal blood directly.

2.

The remaining medium and long chain fatty

acids bind to cytosolic fatty acid binding proteins
and are transported to the endoplasmic reticulum,
where they are re-esterified to form triglycerides
(Fig. 14).

SHORT/MEDIUM CHAIN
FATTY ACIDS (C4-C10)

FABP

MONOGLYCERIDES
CHOLESTEROL
LONG CHAIN
FATTY ACIDS

FABP

Figure 15 Structure and Composition of

Chylomicrons. Chylomicrons consist of droplets
of apolar lipids surrounded by a monolayer of polar
lipids and protein).

MICELLE

Figure 13. Absorption of Fat Digestion

Products (FABP = Fatty Acid Binding Proteins)
3.

The majority of the cholesterol is re-esterified.

Synthesis of !
triglyceride!
and phospholipid!
Synthesis of !
apolipoproteins!
Glycosylation!
of some!
apolipoproteins!

Exocytosis!

Nascent (newly formed) chylomicrons migrate in

secretory vesicles towards the lateral cell membrane
where they fuse and are extruded by exocytosis.
From the lateral intercellular space chylomicrons
pass through gaps in the basement membrane and
enter the central lacteal of the intestinal villus. Short
chain fatty acids are released from the base of the cell
directly into the portal circulation.
5.

Intestinal cells can also produce and secrete

lipoprotein particles of the size of very low
density lipoproteins (VLDL). This is an
important route for cholesterol transport into
blood, and is a major transport pathway during
the fasted state.

Transport of Fat in the Lymph and Blood

Figure 14. Resynthesis of Triglyceride and
Chylomicron Formation (FA = Fatty Acids;
MG= Monoglyceride)
4. Triglycerides, phospholipids, cholesterol and
apolipoproteins
associate
into
droplets
(chylomicrons; Figs. 14 and 15). Synthesis of
apolipoproteins in the rough endoplasmic
reticulum is critical for chylomicrom formation.

From the enterocyte the chylomicrons travel in the

lymph and reach the general circulation via the
thoracic duct. The entire process of fat absorption can
be seen within 30 min. after eating fat.
Lipoprotein lipase in blood removes triglyceride from
the chylomicrons and converts it to fatty acids and
glycerol. The remaining particle consists of
cholesterol and protein. This passes to the liver where
low density lipoprotein binds the cholesterol for
transport.

CARBOHYDRATE DIGESTION AND

ABSORPTION

2.

A daily Western diet contains 200-300g of

carbohydrate; 40-50% of the total food energy
ingested. ~50% is starch, the remainder disaccharides
and monosaccharides. There are variable amounts of
dietary fibre in a meal.

Within 10 minutes of starch entering the

duodenum it is largely broken down by
pancreatic amylase. With both enzymes cleavage
of (1,4) glycosidic linkages produces maltose,
maltotriose and -limit dextrins (Fig. 16); (1,6)
glycosidic bonds are not split.
MALTOSE!

A. Structure
1.

2.

1:6 link!

There are 2 principal types of dietary starch.

amylose is a linear polymer of glucose linked
in an 1,4 glycosidic configuration with a
molecular weight of ~105. Amylopectin is a
branched form of -amylose containing both
(1,4) and (1,6) glycosidic linkages and has a
molecular weight of 106 (Fig. 16).
Dietary fibre forms part of most diets and is
largely resistant to digestion by human intestinal
enzymes. Cellulose, a component of fibre,
consists of glucose molecules linked by (1,4)
bonds.
Important dietary monosaccharides include
glucose and fructose (fruits/vegetables) and
sorbitol (fruits/vegetables and a non-nutritive
sweetener). The major disaccharides include
sucrose (fruits), lactose (milk products), maltose
(malt, beer) and trehalose (mushrooms and
yeast).

MALTOTRIOSE!
1:4 link!

Figure 16. Products of Starch Digestion

by -Amylase
3.

4.

B. Digestion
1.

!-LIMIT DEXTRIN!

Further hydrolysis is accomplished by the brush

border carbohydrases maltase-glucoamylase,
lactase, sucrase-isomaltase and trehalase (Fig.
17). Sucrase-isomaltase (-limit dextrinase) is a
bifunctional enzyme with two active sites.
Ultimately, the majority of dietary carbohydrates
are broken down to glucose, galactose and
fructose for absorption.
Starch and oligosaccharides that reach the colon
are rapidly metabolized by the colonic bacterial
flora to short-chain fatty acids (e.g. acetic,
butyric, propionic). These are used as primary
fuels for colonocytes.

Salivary (-) amylase (ptyalin) initiates starch

digestion in the mouth, but digestion continues
in the bolus of food after it has entered the
stomach.
STARCH
SALIVARY
AMYLASE

PARTIALLY DIGESTED
STARCH
PANCREATIC
AMYLASE

Brush
Border

TREHALOSE

LACTOSE

MALTOTRIOSE MALTOSE

DEXTRINS SUCROSE

TREHALASE

LACTASE

MALTASE-GLUCOAMYLASE

ISOMALTASE SUCRASE

GALACTOSE

GLUCOSE

FRUCTOSE

TRANSPORTER

TRANSPORTER

Figure 17. Digestion of Dietary Starch and Disaccharides.

LUMEN

ENTEROCYTE

INTERSTITIAL
FLUID

Na+ K+

Na+
GLUCOSE/
GALACTOSE

FRUCTOSE

Na+
SGLT1

GLUT5

GLUCOSE/
GALACTOSE

FRUCTOSE

GLUT2

GLUCOSE/
GALACTOSE

GLUT2

FRUCTOSE

PARACELLULAR

PARACELLULAR

Figure 18. Pathways of Glucose, Galactose and Fructose

Transport Across the Intestinal Epithelium

C. Monosaccharide Absorption
1.

2.

3.

4.

5.

The duodenum and upper jejunum have the

highest capacity to absorb sugars. The only
dietary monosaccharides that are well absorbed
are
glucose,
galactose
and
fructose.
Monosaccharide transporters are expressed in
mature villus cells but not crypt cells.
Glucose and galactose are actively taken up into
the brush border epithelial cells via a Na+dependent transporter that has binding sites for
two Na+ and one sugar (SGLT1) (Fig. 18).
Na+ moves into the cell down the
electrochemical gradient created and maintained
by the Na+/K+-ATPase in the basolateral
membranes. This is the driving force for glucose
or galactose transport into the cell against a
concentration gradient.
Fructose absorption is carrier-mediated (GLUT
5) down a concentration gradient (Na+ is not
required).
Transport of glucose or galactose out of the cell
is via a transport protein in the basolateral
membrane (GLUT 2).

PROTEIN DIGESTION AND

ABSORPTION

1.

2.

In the adult 10-15% of protein is digested by

pepsins in the stomach, but gastric digestion of
protein is dispensable.
Proteins are digested to amino acids and
oligopeptides by pancreatic enzymes in the
duodenal lumen (Fig. 19). The major enzymes
involved are the endopeptidases trypsin,
chymotrypsin and elastin, and the exopeptidases
carboxypeptidase A and B. Enterokinase
converts trypsinogen to trypsin and thus initiates
pancreatic enzyme-mediated digestion. (See
Pancreas notes for details).
Protein
Pepsin
Pancreatic Proteases

Polypeptides

Proteases

Di-& TriPeptides

Peptide
Transporter
(Pept-1)

Peptides

Amino Acid Transporters

Amino Acids

Amino Acids

There is a variable protein intake between different

ethnic groups, but the average North American diet
contains 70-100g of protein. In normal individuals
virtually all ingested protein is digested and
absorbed. Intraluminal enzymes, desquamated cells
and plasma proteins are also digested and absorbed.
Protein digestion begins with intraluminal proteases
and is continued by brush border enzymes.

K+
Transporters
Extracellular Fluid

Na+

Figure 19. Digestion of Protein, and Uptake of

Amino Acids and Peptides into Epithelial Cells

7.
3.

4.

Up to 80% of luminal amino acids may be in the

form of di- and tri-peptides. These are
transported by the H+-dependent transporter
Pept-1 (Figs. 19 and 20). Transport is driven by
a Na+/H+ exchanger in the luminal membrane.
Larger oligopeptide products of pancreatic
enzyme digestion are further hydrolyzed to diand tri-peptides by brush border hydrolases,
including aminopeptidases, dipeptidases and
carboxypeptidases (Fig. 20).

At the basolateral membrane there are at least

five amino acid transporters, plus transporters for
peptides.

REFERENCES
Medical Physiology. Boron, W.F. & Boulpaep, E.L.
Updated Edition, 2005, Chapter 44 OR Second
Edition Saunders 2009 & 2012, Chapter 45 (Nutrient
Digestion & Absorption).
Physiology. 6th Edition. Berne, R.M. & Levy M.N.
Mosby 2008. Chapter 29 (The Small Intestinal Phase
of the Integrated Response to a Meal).
Figure 4 is from Medical Physiology, Boron, WF and
Boulpaep, EL, 2012
Figure 5 is from Davenport, H. W. Physiology of the
Digestive Tract, 3rd edition. Chicago: Yearbook
Medical Publishers, 1973
Figures 10-12, 14 & 15 are from the
Gastroenterology Teaching Project; American
Gastroenterological Association.

FOR REFERENCE ONLY

Figure 20. Peptide Digestion and Absorption
by the Brush Border
5.

There are numerous Na+-dependent and Na+independent amino acid transporters in the
luminal membrane of enterocytes. The former
are probably the more important. Specific
transporters may transport either a single type of
amino acid (e.g. acidic) or several different types
(e.g. ASC) (Fig. 20; Table 1)
Transport
System

Apical
B0
ASC
b0,+
X-AG
IMINO
Pat

!
!
Basolateral
L
T
y+L
!

Transporter
cDNA

Amino Acids

Na+dependence

!
B0AT1
ASCT2
rBAT/b0,+AT
EAAT3
IMINO
PAT1
TauT

!
Neutral
Neutral, Anionic
Cationic, Cystine
Anionic
Imino, Glycine
Imino, Glycine
Taurine, ! AAs

!
Yes
Yes
No
Yes
Yes (& Cl-)
No (H+)
Yes

LAT2
TAT1
y+LAT1, y+LAT2

Cystine
Aromatic
Cationic, Neutral

No
No
Yes

Table 1. Amino Acid Transporters

Identified In Human Enterocytes (For
Reference Only)
6.

Some larger peptides enter the enterocyte and are

hydrolyzed intracellularly.

INTESTINAL TRANSPORT OF
MACROMOLECULES
Not all macromolecules are digested before
absorption. This is of both physiological and
pathophysiological importance. For example, the
absorption of the vitamin B12/ intrinsic factor
complex in the ileum is mediated by endocytosis. The
degree of absorption of macromolecules is agedependent.

The Immature Intestine (Newborn)

1.
2.
3.

4.

5.

Macromolecules are ingested by pinocytosis.

The mucosa is leaky and immunologically
deficient
As epithelial cells mature passage of
macromolecules decreases. This phenomenon is
called closure and occurs at about three months
of age.
Mammalian foetuses do not synthesize their own
antibodies, but receive them either by placental
transfer or via colostrum ingested by the
suckling young (Passive Immunization).
In humans, passive immunity is derived from a
combination
of
intrauterine
transport
(globulins) and secretory immunoglobulin A
in mother's milk (colostrum).

FAT-SOLUBLE VITAMINS
The Mature Intestine
In the adult the barrier between host and environment
is not 100% effective and luminal antigenic
materials, including intact microorganisms and
bacterial toxins penetrate this barrier, both normally,
and as the result of inflammatory diseases, e.g.
gastritis, celiac disease.

Food-derived fat-soluble vitamins are transported in

micelles and absorbed passively. Rates of absorption
depend upon the polar side chains. There are two
sources of Vitamin dietary K1 and bacterially-derived
K2. The majority of fat-soluble vitamins absorbed
are transported out of the cell in chylomicrons.

The Gut Associated Lymphoid Tissue (GALT) is

important for defense at this level, and M cells are
responsible for the uptake of much intact protein.

WATER-SOLUBLE VITAMINS

ABSORPTION OF VITAMINS
Vitamins are required in small amounts by the body
as cofactors in numerous biological reactions. They
cannot be synthesized and must be obtained from the
diet. Vitamins are classified as fat-soluble and watersoluble.

There are specific transport systems for uptake of all

of the water-soluble vitamins into enterocytes Table
2). In some cases these involve coupling to the Na+
pump (e.g. vitamin B6), whereas other vitamins are
transported by Na+-independent mechanisms.

Table 2. Mode of Uptake of Water-Soluble Vitamins

Jej = jejunum; Col = colon. Biotin and pantothenic acid are transported by the same transporter: Na+dependent multivitamin transporter; SMVT. In the colon, the majority of the vitamins absorbed are
products of the enteric bacteria.

10