>>Dr. Ketchum: In this video lecture on the gastrointestinal system, we are going to focus
on protein digestion and absorption. So in a typical diet we consume about 125 grams
per day of protein. And these aren’t values for you to memorize, they’re in case you’re
curious on in a typical diet how much we actually ingest. So proteins that we’re actually
going to digest and absorb include those that are consumed in our diet, those proteins that
get secreted into the lumen of the intestinal tract, such as some enzymes. So you do have
some enzymes that get secreted into the lumen and then we break them down. And those proteins
that are sloughed off with cells that line the intestinal track. So we’re talking here
about enterocytes that are sloughed off into the lumen of the GI tract. And so let’s
take a look at sort of a crude diagram of a protein, right? So remember that a protein
consists of a string of amino acids: the monomer are the amino acids, or the subunits are amino
acids. On one end we have a carboxyl group, the COOH. On the other end we have the amine
group, the NH2. And all of these amino acids are held together via peptide bonds. Our protein
digestion products—in other words, when we digest this protein, what do we get? We can
get an individual amino acids as a product, we can get dipeptides, and we can also get
tripeptides. So by individual amino acids we just mean AA-AA. Here would be a dipeptide,
right? It just means two peptides. And I’m just drawing these as pretty short sequences,
and then tripeptides would mean three.
When the proteins are digested you can get these three products, and it’s dependent
upon the enzyme in question. These are the types of proteases. We know that proteases
are a general term for enzymes that break down proteins. So we have two different categories
for proteases: we have endoproteases, and there are exopeptidases. So peptidases: Breaking
an enzyme that breaks down proteins. “Endo” and “exo” is giving you a hint on where
they actually cleave the protein. So an endopeptidase will split the polypeptide at the interior
peptide bond. So for example, it may split or break that peptide bond there. So if that
were to happen, we would get two products; we would have a dipeptide as our products.
And so any time an endopeptidase splits a polypeptide at the interior peptide bonds,
you get small peptide fragments: a dipeptide, or a tripeptide. How many times would you
have to cleave this protein in order to get a tripeptide? Well, you’d have to cleave
it twice, right? So if I cleave this here, that gives me one peptide and I cleave again
over here that gives me a second peptide. And if I cleave over here, that gives me a
third one over here. So by cleaving it twice we get the tripeptides. Now
exopeptidases—think about the name, E X out. So now we’re going to cleave amino acids
from one end of the polypeptide. So if we cleave from the carboxyl end, these will be
called carboxyl peptidases. And you can also have other enzymes called amino peptidases
that cleave at the amine end, and when these things cleave, they’re cleaving off or breaking
off one amino acid at a time. And so they would cleave that amino acid. So the product
then here are individual amino acids.
Let’s focus on zymogens for a minute. So zymogens are inactive storage form of proteases.
These include trypsinogen, they include chymotrypsinogen, and also include
procarboxypeptidase. So these are inactive storage forms, okay? So these are zymogens. These proteases
are stored in zymogen granules. And what we mean by zymogen granules are secretory cells. So these are
secretory cells that contain tripsinogen, chymotripsinogen, and procarboxylpeptidase.
These secretory cells then have to be secreted via exocytosis from the acinar cells. So remember,
when zymogens are produced by the pancreas, they’re produced by these acinar cells and
then released into the duct and then, they get activated by proteolytic activation, which
we’re going to discuss later. Let’s first focus on where protein digestion begins. So
we have protein digestion taking place first in the stomach, and so the chief cells that
are part of this gastric gland or gastric mucosa, the chief cells secrete pepsinogen.
Pepsinogen is a precursor enzyme. The parietal cells secrete hydrogen ions that will then
combine with chloride ions to form hydrochloric acid. So a lot of times you’ll see that
parietal cells secrete HCL, which is true, in essence.
So how does this work? So when the parietal cell or the chief cells, rather, synthesize
and secrete pepsinogen, it passes through this gastric pit and up into the lumen of
the stomach. The hydrochloric acid does the same. When the parietal cells synthesize and
secrete it, it moves its way up into the lumen of the stomach as well. Hydrochloric acid
then is what’s going to activate your pepsinogen. Remember we said pepsinogen is a precursor?
Well when it’s activated, now we have the active form of pepsin. So pepsin is an endopeptidase.
So we know that pepsin is going to start cleaving proteins at those interior bonds, and the
end result will be smaller peptide fragments. And so this protein digestion has started
in the stomach. Protein digestion also occurs in the small intestine, and that involves
pancreatic proteases. And so earlier I described to you the zymogens. And I said that those
zymogens were trypsinogen, chymotrypsinogen, and procarboxypeptidase. So those are made
by the pancreas. These are all inactive forms of the enzyme, or in other words, they’re
precursor enzymes. So trypsinogen is a precursor to trypsin; chymotrysinogen is a precursor
to chymotrypsin. Procarboxypeptidase is a precursor to carboxy peptidase. So the active
forms of the enzymes are circled in red for you. These are the active forms, meaning the
ones that can catalyze reactions. So then we also have brush border proteases. Brush
border proteases are again located in the microvilli and so of the brush border. So
we have two groups: aminopeptidases and enterokinase. Before we leave this slide, I would like to
first discuss which of these are endopeptidases and which are exopeptidases. We already discussed
pepsin as an endopeptidase; trypsin and chymotrypsin are also endopeptidases. Carboxypetidase and
aminopeptidase, think about those names. “Carboxy,” “amino,” those are exopeptidases. So what
end of the protein does carboxypeptidase start at? Well, it starts cleaving at the carboxyl
end. What end of the protein does aminpeptidase start cleaving at? It will begin cleaving
at the amine end. And then there’s enterokinase. This is a proteolytic enzyme, a proteolytic
enzyme; it’s responsible for activating other enzymes. So let’s look at how this
is going to work. So we have the pancreas, here’s the lumen of the small intestine.
And we know that within the pancreas we have acinar cells that are producing trypsinogen,
chymotripsinogen, and procarboxypeptidase. We know that these are all packaged up inside
of a secretory cell, that zymogen that we talked about. So these are inactive forms
of the enzyme. How do they become activated? When these enzymes get released into the small
intestine, think back to what sphincter needs to be open in order for these enzymes to enter
into the lumen of the small intestine? And this, by the way, is the duodenum—that’s
the region of the small intestine that we are in, okay? So one of the sphincters has
to be open. Which sphincter is that?
So it all begins with trypsinogen and enterokinase. Enterokinase, remember, is that brush border
enzyme. So it’s a proteolytic enzyme that converts trypsinogen into trypsin. So remember,
trypsin is the active form of the enzyme. So trypsin, then, is going to help cause the
conversion of chymotrypsinogen into chymotrypsin, which is also the active form of the enzyme.
Which trypsin then is going to cause procarboxypeptidase to be converted into its
active form, carboxy peptidase. So what are the products then by the activation of these
proteases? Since trypsin is an endopeptidase, that will give you di and tripeptides. Chymotripsin
is also an endopepsidase, so that will give you di and tripeptides. Carboxypeptidase,
though, is an exopeptidase, so that will give you individual amino acids. So then how do
we absorb these products into the blood? Focus on absorption of the amino acids. As you can
tell, this is a pretty blank diagram. This is going to be the lumen of the small intestine;
you have your epithelial cell. We’re going to have a carrier protein that we’re going
to put in blue here that’s affiliated with ATP, and what this thing is going to be doing
is it’s going to be pumping sodium out of the cell and potassium into the cell. And
so once again, that’s your form of primary active transport. On the apical membrane you’re
going to have another carrier protein, and I’ll just draw this in as the blue carrier
protein here. We’re going to be transporting sodium along with amino acids. So if we’re
transporting sodium in, it must be moving from a high concentration in the lumen toward
a low concentration in the lumen, because the pump is pumping it out. In conjunction
with that then, when sodium moves down its gradient, that provides the indirect energy
to move your amino acids into the epithelial cell. So the type of transport—let’s just
label this number two—the type of transport on this apical membrane is sodium amino acid
co-transport, which once again is a type of secondary active transport. But we haven’t
gotten our amino acids into the blood yet, and that’s our goal. So now what we have
inside of this epithelial cell is a high concentration of amino acids. So can amino acids freely
diffuse across the membrane? Hopefully you answered no. So here is my carrier
protein on the basolateral membrane, and these amino acids are going to use that carrier
protein to go from a high concentration in the cell toward a low concentration. So number
three then is facilitated diffusion. That’s how we can absorb amino acids, but we also
said on the previous slide that some of our products are di and tripeptides.
All right, so this is how we’re going to be absorbing those. We still have primary
active transport occurring on the basolateral membrane, and it’s still going to be pumping
sodium out and potassium in. So there’s a low concentration of sodium in the cell
and high concentration of potassium inside the cell. This is going to involve secondary
active transport on the apical membrane. So here’s my carrier protein, but this time
it’s a little different than what you’ve seen before. This time what we’re going
to do is we are going to use di and tripeptides, and they’re going to be moving into the
cell. So these are going to be your di and tripeptides, and we’re also going to be
moving some hydrogen ions. So this is why it’s different than before. So the hydrogen
ions are at a high concentration in the lumen, and this is still the lumen of the small intestine.
So hydrogen ions are going from high to a low concentration, which is going to help
create the energy to drive your di and your tripeptides from a low concentration in the
lumen to a higher concentration in the epithelial cells. So now then we’ve got di and tripeptides
inside the epithelial cell. So the di and tripeptides then will get converted into individual
amino aids via yet another enzyme. These are called cytoplasmic peptidases. And so these
cytoplasmic peptidases breakdown or catalyze the reaction of your di and tripeptides into
individual amino acids. Then those individual amino acids can use facilitated diffusion
to go from a high concentration inside the epithelial cell to a low concentration in
the blood. So that explains how we absorb our amino acids from the di and the tripeptides.
You’ve got—still have to break down a di and a tripeptide into individual amino
acids before you can actually absorb it. So that concludes the digestion and absorption
of proteins.