Human Physiology – Protein Digestion and Absorption

Human Physiology – Protein Digestion and Absorption


>>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.