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Digestion of proteins and

uptake of amino acids

Dr. Solomon Genet


MUHAS

Topics to be covered
Digestion of proteins and enzymes
involved
Uptake of amino acids by cells
The -glutamyl cycle

Lecture objectives
To elucidate the enzymatic digestion of
dietary proteins
To describe the different enzymes involved
in the digestion of proteins
To analyze the way amino acids are taken
up by cells
To comprehend the -glutamyl cycle

Digestion of Proteins
Entry of dietary protein into the stomach
stimulates the gastric mucosa to secrete the
hormone gastrin.
Gastrin stimulates the secretion of HCl by the
parietal cells and pepsinogen by the chief cells
of the gastric glands.
HCl has antiseptic property and denatures
proteins rendering internal parts accessible for
enzymatic hydrolysis.

Digestion of Proteins
Pepsinogen, an inactive precursor, or zymogen, is
converted to active pepsin by the enzymatic action of
pepsin itself.
In the stomach, pepsin hydrolyzes proteins at peptide
bonds on the amino-terminal side of the aromatic
amino acid residues (Phe, Trp, Tyr).
When stomach contents pass into the small intestine,
the low pH triggers secretion of the hormone secretin
into the blood.
Secretin stimulates the pancreas to secrete
bicarbonate into the small intestine to neutralize the
gastric HCl, abruptly increasing the pH to about 7.

Digestion of Proteins
Digestion of proteins now continues in the small
intestine through secretion of cholecystokinin,
which stimulates secretion of many peptidases.
These include Trypsinogen, Chemotrypsinogen,
and Procarboxypeptidase A and B (inactive forms)
Trypsinogen changed to trypsin by
enteropeptidase and trypsin further activates
itself and the other inactive precursors.
Synthesis of the enzymes as inactive forms
protects the exocrine cells from destructive
proteolytic attack (self digestion).

Digestion of Proteins
The pancreas further protects itself against selfdigestion by making a specific inhibitor, a
protein called pancreatic trypsin inhibitor.
Pepsin, trypsin, and chymotrypsin have
different amino acid specificities.
Trypsin cleaves peptide bonds from the
carboxyl termini of basic amino acids (Lys,Arg)
Chemotrypsin cleaves peptide bonds from the
carboxyl ends of aromatic amino acids.

Gastric glands
stomach

Parietal cells
Chief cells

pancreas

Low pH
Pepsinogen

Pancreatic duct
pepsin
pH 7

Zymogens, active proteases

Small intestine

Part of the human digestive (gastrointestinal) tract.

Exocrine cells
Of pancreas
Rough ER
Zymogen
granules

Villi of small
intestine

Digestion of Proteins
Degradation of the short peptides in the small
intestine is then completed by other entestinal
peptidases.
Carboxypeptidases A and B (both of which are
zinc-containing enzymes), remove successive
carboxyl-terminal residues from peptides, and
an aminopeptidase that hydrolyzes
successive amino-terminal residues from short
peptides.
The resulting mixture of free amino acids is
transported into the epithelial cells lining the
small intestine.

Absorption of amino acids


Amino acids are absorbed by carrier mediated
transport.
Small intestine has high capacity to absorb
free amino acids and dipeptides.
Most L-amino acids are transported across the
epithelium against a concentration gradient.
Luminal concentration are usually higher than
plasma levels (0.1-0.2mM).

Absorption of amino acids


Seven transporter proteins have been identified
on the brush border of the small intestine.
These are used for uptake of amino acids.
There are both Na+ cotransport and non Na+
dependent transport systems of amino acids.
Amino acids are not chemically modified during
membrane transport.
There have been observed genetic defects in
amino acid transporter proteins (Hartnup
disease).

Amino acid transporters


The lumenal plasma membrane of the
absorptive cell bears at least four sodiumdependent amino acid transporters - one
each for acidic, basic, neutral and amino acids.
These transporters bind amino acids only after
binding sodium. The fully loaded transporter
then undergoes a conformational change that
dumps sodium and the amino acid into the
cytoplasm, followed by its reorientation back to
the original form.

Amino acid transporters


Thus, absorption of amino acids is also absolutely
dependent on the electrochemical gradient of sodium
across the epithelium.
Further, absorption of amino acids, like that of
monosaccharides, contributes to generating the
osmotic gradient that drives water absorption.
The basolateral membrane of the enterocyte contains
additional transporters which export amino acids from
the cell into blood. These are not dependent on
sodium gradients.

Absorption of short peptides


There is virtually no absorption of peptides
longer than four amino acids.
However, there is abundant absorption of diand tripeptides in the small intestine.
These small peptides are absorbed into the
small intestinal epithelial cell by cotransport
with H+ ions via a transporter called PepT1.

Abnormality in amino acid absorption


Hartnup disease: name given after the family in
which the defect was observed.
Defect in neutral amino acids transporter
protein hence inability of renal and intestinal
epithelial cells to absorb such amino acids.
Acute pancreatitis: disease caused by
obstruction of pancreatic secretion pathway.
The zymogens are converted to their active
forms prematurely and destroy the pancreatic
cells.
This damages the organ causes severe pain
that can be fatal.