Ok, so now that we’ve talked about proteins and carbohydrates, lipids, membranes,
transport proteins – it’s time to start putting it all together; and the way we’re going
to do this is we are going to talk about how we get energy from food. We’ll start with
digestion and go all the way down to the molecular level.

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Biochemistry:
A Short Course
Fourth Edition

CHAPTER 14
Digestion: Turning
a Meal into Cellular
Biochemicals

Tymoczko • Berg • Gatto • Stryer

© 2019 W. H. Freeman and Company.

The sections of this chapter are going to be (1) digestion prepares large biomolecules
for use in metabolism. And that’s basically the main goal of digestion, is to break
down things into smaller parts. It breaks down (2) proteins into amino acids, and (3)
carbohydrates into monosaccharides. And it takes (4) lipids, which are already quite
small, but solubilizes them and creates a method for transporting them throughout
the body.

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Chapter 14: Outline

14.1 Digestion Prepares Large Biomolecules for Use in
Metabolism

14.2 Proteases Digest Proteins into Amino Acids and
Peptides

14.3 Dietary Carbohydrates Are Digested by
Alpha-Amylase

14.4 The Digestion of Lipids Is Complicated by Their
Hydrophobicity

So – large molecules in food get broken down into smaller ones. And when we talk
about large molecules, we’re talking a lot about starches, which are really long chains
of polysaccharides, and proteins, which are really long chains of amino acids. These
amino acids and monosaccharides then get processed in the body to smaller chunks.
Most notably, there is the acyl group which is attached to the coenzyme A in the form
acetyl CoA. And this acyl group gets broken down even farther to complete oxidation
and the formation of ATP.

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So digestion begins, of course, in the mouth. And that’s just the matter of breaking up
the large chunks of food into smaller pieces. And one of the most important aspects
of that is the increase in surface area, which will allow the digestive enzymes to reach
the food particles/molecules more easily. And there are also some enzymes in the
mouth, salivary amylase for example, which start the digestion process. Once the
food gets down into the stomach, it’s a highly acidic environment which tends to
denature the proteins and therefore make them be able to be digested further by
proteolytic enzymes. The protease pepsin is the main one in the stomach, and it’s
remarkable because of its ability to remain active and not get denatured in the acidic
environment. So as the food moves into the small intestine, the first thing that needs
to be done is the acid needs to be neutralized, and that’s done with sodium
bicarbonate (very similar to how you neutralize vinegar with baking soda). {Lipases}
are also added from the {pancreas} to help to break down the fats, and a few other
enzymes are put into the mix to help break down the other types of molecules.

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Section 14.1 Digestion Prepares Large
Biomolecules for Use in Metabolism

Learning objective 1: Describe how dietary proteins,
carbohydrates, and lipids are digested.

• Digestion begins in the mouth with the formation of a more readily
digestible aqueous slurry by the process of chewing food.

• The acidic environment of the stomach denatures proteins, exposing
their innards to proteolytic enzymes. The stomach protease pepsin
begins the digestion of proteins

• As the partially digested food moves into the small intestine, the
pancreas secretes sodium bicarbonate to neutralize the acid, lipases
to facilitate the digestion of fats, and enzymes to digest all types of fuel
molecules.

Figure 14.1 Pizza. Foods provide a pleasurable means of obtaining energy and
building blocks for biological systems. [Mode/Ian O’Leary/age fotostock.]

A pizza is an excellent example of all of these things, where you have the proteins in
the meat, you have the carbohydrates in the crust, and you have the lipids in the
cheese.

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Image of Pizza

So when food goes from the stomach to the intestine, it stimulates secretion of two
key hormones: secretin and cholecystokinin. Secretin causes the release of sodium
bicarbonate to neutralize the stomach acid. And cholecystokinin releases further
digestive enzymes from the pancreas as well as bile salts from the gall bladder.

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Section 14.2 Proteases Digest Proteins
into Amino Acids and Peptides

Learning objective 2: Explain how the release of
pancreatic enzymes is coordinated with digestion in the
stomach.

• The movement of food from the stomach to the intestine
stimulates the secretion of two key hormones by cells of
the small intestine.

• Secretin causes the release of sodium bicarbonate,
which neutralizes stomach acid.

• Cholecystokinin (CCK) stimulates the release of digestive
enzymes from the pancreas as well as the secretion of
bile salts from the gallbladder.

Figure 14.3 The hormonal control of digestion. Cholecystokinin (CCK) is secreted by
specialized intestinal cells and causes the secretion of bile salts from the gallbladder
and digestive enzymes from the pancreas. Secretin stimulates sodium bicarbonate
(NaHCO3) secretion, which neutralizes the stomach acid. [After D. Randall, W.
Burggren, and K. French, Eckert Animal Physiology, 5th ed. (W. H. Freeman and
Company, 2002), p. 658.]

And here’s a nice diagram of that, with food entering the stomach from the top, being
broken down by hydrochloric acid and pepsin into oligopeptides and other initial
digestion products. These green arrows, with the plus signs, show you that there is a
stimulation going on. (It kind of looks like the stimulation is occurring when the
oligopeptides are in the stomach, but I think it actually starts once they have entered
the small intestine.) And the {stomach acid stimulates} the release of the hormone
secretin which then stimulates the pancreas to release sodium bicarbonate and
neutralize the acid. The other initial digestion products stimulate the cholecystokinin,
which stimulates the pancreas to release a host of other digestive enzymes, and bile
salts from the gall bladder.

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Diagram of the Hormonal Control of
Digestion

Now, the enzymes created by the pancreas are not secreted as active enzymes
because if they were active they would start digesting the pancreas. So they are
secreted as precursors, and those are called proenzymes or zymogens. And those are
basically amino acid chains that have extra amino acids attached to them. And those
amino acids can be cleaved by enzymes inside the body, which then activate the
digestive enzymes. The enzyme that starts this process is called enteropeptidase. And
that’s not secreted by the pancreas, but by the intestinal cell walls. So these
zymogens, they enter into the intestines and there they start becoming activated. The
first thing that happens is enteropeptidase converts trypsinogen (that’s how you say a
zymogen, it’s like basically the name of the enzyme with “-ogen” added to the end, so
trypsin is the enzyme and trypsinogen is the zymogen, the proenzyme) – so
trypsinogen enters into the intestines and enteropeptidase cleaves it. And then
trypsin starts cleaving the other proenzymes to create active enzymes.

These enzymes, in cooperation with peptidases on the surfaces of the intestinal cells,
break down all of these long amino acid chains into either individual amino acids or
two or three amino acid groups, which are then transported into the cells of the
lining of the intestinal wall where they are broken down further into individual amino
acids and then released into the blood.

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Most Digestive Enzymes Are Secreted as
Inactive Precursors

• The enzymes of the pancreas are secreted as precursors called
proenzymes or zymogens.

• Enteropeptidase, secreted by intestinal cells, converts inactive
trypsinogen into active trypsin. Trypsin, in turn, activates the other
proenzymes.

• Proteins are digested into amino acids and small oligopeptides. The
amino acids are absorbed by transporters. Peptidases on the surface
of intestinal cells cleave the oligopeptides into di- and tripeptides,
which are transported into the intestinal cells and degraded into amino
acids.

• The amino acids are subsequently released into the blood.

Here is a short list of some of the gastric and pancreatic zymogens, and their active
forms, and where they are manufactured within the body.

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Table 14.1 Gastric and Pancreatic Zymogens

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Zymogen activation by proteolytic cleavage. Enteropeptidase initiates the activation
of the pancreatic zymogens by activating trypsinogen to form trypsin, which then
activates chymotrypsinogen and the other zymogens. Active enzymes are shown in
yellow; zymogens are shown in orange.

This is a diagram of the activation cascade of all of these zymogens. Starting with
enteropeptidase at the top – that cleaves trypsinogen in to trypsin. Trypsin actually
can cleave trypsinogen in to trypsin as well, so there’s a bit of a feedback mechanism
there. And then trypsin also is responsible for cleaving off the inhibitory parts of
these other proenzymes and making them active.

Yeah – I’d like to be a little bit more specific about what these inhibitory parts are: it’s
just an extra bunch of amino acids that somehow get in the way of the active sites of
these enzymes. And so when they are present, the enzymes can’t do what they’re
supposed to do, but if they get cut away, the active site becomes exposed and the
enzyme is able to break down its targets.

Figure 14.4 The digestion and absorption of proteins. Protein digestion is primarily a
result of the activity of enzymes secreted by the pancreas. Peptidases associated with
the intestinal epithelium further digest proteins. The amino acids and di- and
tripeptides are absorbed into the intestinal cells by specific transporters. Free amino
acids are then released into the blood for use by other tissues.

So all of this takes place in the lumen of the intestine (you know, just the inside of the
tube), and when {proteins} are broken down either into 1-, 2-, or 3-amino-acid
groups, they get transported into the intestinal cells in the form of amino acids, or
dipeptides, or tripeptides. The dipeptides and tripeptides are then further broken
down by peptidases into individual amino acids, and all of those individual amino
acids are transported into the blood.

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Diagram of the Digestion and Absorption
of Proteins

So our primary source of carbohydrates is starch. And there are a lot of enzymes that
are involved, but the most important one is alpha-amylase. That is able to digest
alpha-1,4 bonds in starches but not alpha-1,6 bonds. Remember, it’s the alpha-1,6
bonds where the starches branch. And other enzymes are involved breaking down
the smaller particles further, including sucrose and lactose, which are common
disaccharides which get broken down into individual monosaccharides before being
absorbed by the intestinal cells.

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Section 14.3 Dietary Carbohydrates Are
Digested by Alpha-Amylase

• Our primary source of carbohydrates is starch.

• Several enzymes participate in carbohydrate digestion.

• α-Amylase initiates digestion by cleaving α-1,4 bonds but
not α-1,6 bonds.

• Other enzymes, including α-glucosidase and α-dextrinase,
complete the digestion.

• Sucrose and lactose, two common disaccharides, are
digested by sucrase and lactase, respectively.

Figure 14.5 The digestion of starch by a-amylase. Amylase hydrolyzes starch into
simple sugars. The α-1,4 bonds are shown in green. The α-1,6 bonds are red. The sites
of α-amylase digestion are indicated by the small green arrows.

So here’s a diagram of that. You can see up at the top a starch molecule with a long
chain connected by alpha-1,4 linkages and a smaller chain connected to the long
chain by an alpha-1,6 linkage. That is all broken down first by alpha-amylase, and you
can see the places where it’s broken apart with the green arrows up at the top. And
individual components that are created could be maltotriose (just three glucoses
stuck together), an alpha-limit dextrin (four glucoses with an alpha-1,6 linkage in the
middle), maltose (is just two glucose) and then individual glucose.

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Diagram of the Digestion of Starch by
α-amylase

Figure 14.6 Uptake of monosaccharides. The results of carbohydrate digestion,
primarily glucose, galactose, and fructose, are transported into the intestinal cells by
specific transport proteins. The carbohydrates also exit the cell with the assistance of
transport proteins.

Once they are in monosaccharide form, they are transported into the intestinal cells
by transporter proteins, like SGLT or Glut5, and then from there transported into the
blood by the Glut2 transport protein.

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Diagram of the Uptake of
Monosaccharides

This is a slightly better diagram, I think, which starts out with starch glycogen at the
top, and alpha-amylase breaks that down. 30% of it is broken down into alpha-limit
dextrins, which are then degraded by alpha-dextrinase into individual glucose
molecules. And then, 70% is broken down into maltooligosaccharides, which is either
from 2 to 9 glucoses in length. And you can see the breakdown of the sizes of those.
And those are broken down further by glucoamylase in the intestinal membrane. And
those individual glucoses are then transported into the interior of the cell by the
SGLT1 protein. And that protein we’ve seen before in Figure 12.20 – that’s the
glucose-sodium-cotransporter {symporter}. Sucrose and lactose get broken down by
sucrase and lactase, as you can see. And then, the individual elements of those, the
glucose, galactose, and fructose are all transported in by the SGLT1 and GLUT5
transporters.

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Figure 12.19 Secondary transport. The ion gradient set up by the Na+–K+ ATPase can
be used to move materials into the cell through the action of a secondary transporter
such as the Na+-glucose symporter.

So here is that SGLT1 transporter, and it’s that sodium glucose cotransporter that
we’ve discussed before. You can see on the left the ATPase pumping out sodium /
pumping in potassium, creating a sodium gradient, and the SGLT1 transporter is
utilizing that sodium gradient to drive the import of glucose into the internal parts of
the cell.

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The SGLT1 Transporter

SGLT

Now fats are a little bit trickier. They are primarily in the form of triacylglycerols. And
those form lipid droplets which are not soluble in water. So one of the ways those get
broken down is by the insertion of bile salts from the gall bladder. These bile salts are
amphipathic molecules, like a detergent that have water soluble parts and also
hydrophobic parts. So the hydrophobic parts will associate with the lipid droplets and
then the hydrophilic parts will help break those droplets apart. Lipases from the
pancreas initially take triacylglycerols and chop off two of the fatty acids leaving a
monoacylglycerol. And then these smaller products exist as micelles (and I’ll discuss
those in a second), which are then absorbed by the intestinal epithelial cells, where,
inside those cells, it remakes them into triacylglycerols. This takes place in the
smooth endoplasmic reticulum. And the triacylglycerols are then packaged with
cholesterol and proteins into particles called chylomicrons, which are then secreted
into the lymph system, and from there into the blood so that they {will be} able to be
absorbed by the tissues.

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Section 14.4 The Digestion of Lipids Is
Complicated by Their Hydrophobicity

• Triacylglycerols from the diet form lipid droplets in the stomach. Bile
salts, secreted by the gallbladder, insert into the lipid droplets,
rendering them more accessible to digestion by lipases.

• Lipases, secreted by the pancreas, convert the triacylglycerols into two
fatty acids and monoacylglycerol.

• The digestion products are carried as micelles to the intestinal
epithelium cells for absorption.

• In the intestine, triacylglycerols are re-formed from free fatty acids and
monoacylglycerol and packaged into lipoprotein transport particles
called chylomicrons.

• The chylomicrons eventually enter the blood so that the triacylglycerols
can be absorbed by tissues.

Figure 14.7 Glycocholate. Bile salts such as glycocholate facilitate lipid digestion in
the intestine.

So this is an example of a bile salt and I think you’ll recognize the steroid nucleus –
similar in structure to cholesterol – and that is the lipid portion that associates with
the hydrophobic parts of the fatty acids. And then the hydrophilic parts {oxygens and
nitrogen} allow the complexes to be dissolved more completely in water so that
they’re able to be digested by lipases.

Unlike cholesterol, there are a few more hydroxyl groups there on the steroid
nucleus, and those help to make it more soluble in water. So the steroid nucleus will
associate with these hydrophobic triacylglycerols and then the hydroxyl portions will
help them to become more solubilized.

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Structure of Glycocholate

Figure 14.8 The action of pancreatic lipases. Lipases secreted by the pancreas
convert triacylglycerols into fatty acids and monoacylglycerol for absorption into the
intestine.

And this is just a very simple diagram of how that happens {lipase digestion of
triacylglycerols, that is}, with the lipase removing first one and then a second acyl
group from the triacylglycerol, leaving a monoacylglycerol.

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Diagram of the Action of Pancreatic Lipases

Figure 14.9 A diagram of a section of a micelle. Ionized fatty acids generated by the
action of lipases readily form micelles. The hydrocarbon chains (green) are on the
inside and the carboxylic acids (red) are on the surface of the micelle.

So if you remember the lipid bilayer, that was made with phospholipids that had a
hydrophilic head group that was represented by a red ball, and then two tails which
were represented by green lines. And because there were two tails, those tended to
stack side by side in more or less straight arrangements. But when you have only one
tail, then they are somewhat triangular shaped, and the top parts are able to form a
spherical shell around the internal hydrophobic parts. This arrangement is called a
micelle. So this is one of the first ways that these lipids are processed to be absorbed
by the body.

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Diagram of a Section of a Micelle

Figure 14.10 Chylomicron formation. Free fatty acids and monoacylglycerols are
absorbed by intestinal epithelial cells. Triacylglycerols are resynthesized and packaged
with other lipids and proteins to form chylomicrons, which are then released into the
lymph system.

These micelles then interact with fatty acid binding proteins in the intestinal cells in
the membranes, and those are transport proteins which transport those individual
fatty acids into the internal parts of the intestinal cell. Now remember, they cannot
diffuse across the cytoplasm, so they need to be carried, or need to stick to a protein
– in this case, we call it the fatty acid transport protein – which would have (as you
might imagine) a hydrophobic area that would allow it to bind to the hydrophobic
parts of the fatty acid, and a hydrophilic area which allows it to be dissolved in the
cytoplasm. Those fatty acid transport proteins then release the fatty acids into the
smooth endoplasmic reticulum, where they are reformed into triacylglycerols, and
then combined with phospholipids, cholesterols, and proteins into chylomicrons,
which are then secreted into the lymph system. And eventually from the lymph
system they get into the blood for distribution all over the body. But this is an
important method of delivering these lipids, because they are not soluble in water, so
it creates these lipoprotein particles that ARE soluble in water, with the
triacylglycerols in the center.

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Diagram of Chylomicron Formation

FABP = Fatty Acid Binding Protein
FATP = Fatty Acid Transport Protein
SER = Smooth Endoplasmic Reticulum
TAG = Triacylglycerols