Proteins
Digestion and absorption of proteins
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The protein load received by the gut is derived from
two primary sources:
70-100 g dietary protein, and
35-200 g endogenous protein,
the latter either as secreted enzymes and proteins in
the gut or from intestinal epithelial cell turnover
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In healthy adults, only 1-2 g nitrogen, equivalent to
6-12g protein, are lost in the feces on a daily basis
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Thus, the digestion and absorption of protein is
extremely efficient
Peptidases hydrolyse proteins
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Proteins, like other dietary macromolecules, are
broken down by hydrolysis of specific peptide
bonds and hence the enzymes involved are termed
‘peptidases’
These enzymes can either cleave internal peptide
bonds (i.e. endopeptidases) or cleave off one amino
acid at a time from either the –COOH or –NH2
terminal of the polypeptide (i.e. they are
exopeptidases subclassified into carboxypeptidases
, and aminopeptidases, respectively)
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The endopeptidases cleave the large
polypeptides to smaller oligopeptides, which
can be acted upon by the exopeptidases to
produce the final products of protein digestion,
amino acids, di- and tripeptides, which are
then absorbed by the enterocytes
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Depending on the source of the peptidases, the
protein digestive process can be divided into
gastric, pancreatic and intestinal phases
A. Digestion of proteins by gastric secretion
The digestion of proteins begins in the stomach, which
secretes gastric juice, a unique solution containing
hydrochloric acid and the proenzyme pepsinogen:
1. Hydrochloric acid:
Stomach acid is too dilute (pH 2-3) to hydrolyze
proteins; however, the acid functions to kill some
bacteria and to denature proteins, making them
more susceptible to subsequent hydrolysis by
proteases
Overview of protein digestion
2. Pepsin:
This acid-stable endopeptidase is secreted
by the serous cells of the stomach as an
inactive zymogen (or proenzyme),
pepsinogen
In general, zymogens contain extra amino
acids in their sequences, which prevent them
from being catalytically active
Note: Removal of these amino acids
permits the proper folding required for an
active enzyme
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Pepsinogen is activated to pepsin either by
HCL, or autocatalytically by other pepsin
molecules that have already been activated
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Pepsin releases peptides and a few free
amino acids from dietary proteins
B. Digestion of proteins by pancreatic
enzymes
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On entering the small intestine, large
polypeptides produced in the stomach by the
action of pepsin are further cleaved to
oligopeptides and amino acids by a group
of pancreatic proteases
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These enzymes, like pepsin, are
synthesized and secreted as inactive
zymogens
1. Release of zymogens:
The release and activation of the pancreatic
zymogens is mediated by the secretion of
cholecystokinin and secretin, two polypeptide
hormones of the digestive tract
2. Activation of zymogens:
Enteropeptidase, an enzyme synthesized by and
present on the luminal surface of intestinal mucosal
cells of the brush border membrane, converts the
pancreatic zymogen trypsinogen to trypsin by
removal of a hexapeptide from the NH2-terminus of
trypsinogen
Trypsin subsequently converts other trypsinogen
molecules to trypsin
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Enteropeptidase thus unleashes a cascade
of proteolytic activity, because
trypsin is the common activator of all the
pancreatic zymogens
3. Specificity:
Each of these enzymes has a different
specificity for the amino acids R groups
adjacent to the susceptible peptide bond
Cleavage of dietary proteins by
pancreatic proteases
Products of pancreatic digestion
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1.
2.
Thus, the products of digestion by
pancreatic enzymes are:
Oligopeptides
Amino acids
Endopeptidases, dipeptidases and aminopeptidases
complete the digestion of proteins
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The final digestion of di- and oligopeptides is
dependent on membrane-bound small
intestinal endopeptidases, dipeptidases and
aminopeptidases
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The end products of this surface enzyme
activity are free amino acids, di- and
tripeptides
Enzymes responsible for protein digestion
Absorption of amino acids di-, and
tri-peptides
Free amino acids, di- and tripeptide are
absorbed across the enterocyte membrane
by specific carrier-mediated transport
 Amino acids are transported by specific
active transporters showing mechanisms
which are similar to ones active in glucose
transport
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1.
2.
3.
4.
5.
6.
These Na dependant symporters are located at the
brush- border membrane
This is an indirect active process
At least six specific symporter systems have been
identified as follows:
Neutral amino acid symporter for a.a. with short or polar sidechains(Ser, Thr, Ala)
Neutral amino acid symporter for aromatic or hydrophobic
side chains (Phe, Tyr,Tryp, Met,Val,Leu,Ileu)
Imino acid symporter (Pro, OH-Pro)
Basic amino acid symporter (Lys, Arg, Cys)
Acidic amino acid symporter ( Asp, Glu)
β - amino acid symporter ( β- Ala, Tau)
These transporter systems are also
present in the renal tubules and
 defects in their constituent protein
structure can lead to disease( e.g. Hartnup
disease)
 Pathologies can be produced in both the
kidney and intestine
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Symporters for di-, and tri-peptides
These are:
 Present in the brush- border surface
 H+- dependant
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Di- and tripeptides are further hydrolyzed to
their constituent amino acids inside the
enterocyte
The final transfer is; therefore; of free amino
acids across the contraluminal plasma
membrane into the portal blood system
 Na- independent transporters are present in
the contraluminal surface, allowing a.a.
facilitated transport to the portal vein
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Digestion and absorption of proteins
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After a protein-rich meal, protein digestion takes place
in the small intestine
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The amino acids released are absorbed by intestinal
epithelial cells
A large proportion of amino acids are transaminated
to alanine, which is released into the portal vein and
taken to the liver
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Therefore, alanine is the major amino acid secreted by
the gut and the principal carrier of nitrogen in the
plasma
Defects in protein digestion and
absorption
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For a number of reasons, protein absorption might be
incomplete
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Some of the proteins, because of their physical or
chemical structure, are resistant to proteolytic
attack and therefore pass through the small intestine
relatively unmodified
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Furthermore, the absorption of free amino acids and
peptides may be less than 100%, particularly if gut
function is impaired
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This occurs in a number of clinical conditions,
such as intestinal infection or injury, and
when certain ‘antinutritional’ factors such as
lectins or trypsin inhibitor proteins are
present in the diet
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This unabsorbed protein or amino acid then
passes through into the colon
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Metabolism by the colonic microflora then occurs,
but
the amino acids are no longer available to the
body, and
are excreted in the faeces, mainly in the form of
bacterial protein.
Abnormalities in protein digestion
 In individuals with a deficiency in pancreatic
secretion ,for example due to :
chronic pancreatitis,
cystic fibrosis, or
surgical removal of the pancreas,
 the digestion and absorption of fat and protein is
incomplete
 This results in the abnormal appearance of lipids,
called “steatorrhea” , and undigested protein in
the feces
Coeliac Disease
Characterized by severe mal-absorption
and specific diagnostic features exhibited
by the intestinal mucosa
 The histological changes are due to the
interaction of gluten, the principal protein of
wheat, with the epithelium
 The deficit is located within the mucosal
cells, and permits certain polypeptides;
resulting from digestion of gluten; to exert
local effects within the intestine, and to be
absorbed, inducing an antibody response
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The intolerance is for gliadin portion of
gluten ( found in wheat and several other
grains)
Medical history
Diarrhea
 Abdominal bloating
 Weight loss
Laboratory Features:
 Anemia, Hgb of 9g/dl
 Low serum iron, ferritin and Vit. B12
 Low RBC folate
 Antibodies to gluten and its fractions are found in
serum
Histopathologigal features:
 Biopsy demonstrated flattening of the mucosal
surface, villous atrophy and disappearance of
microvilli( reduction of surface, thus greatly reduced
absorption
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Nutritional Management
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All gluten containing products should be
removed from diet permanently(gluten-free diet)
Avoid wheat, barley, rye, and all products made
with these grains
Oats may be tolerated, but this needs testing
Read labels carefully, because gluten containing
grains are added to many products
Hartnup’s disease
A rare inherited disease of neutral amino acids
symporter for aromatic or hydrophobic side
chains (Phe, Tyr,Tryp, Met,Val,Leu,Ileu )
leading to malabsorption of these a.a.s
 Produces a clinical syndrome mimicking
pellagra (niacin deficiency- the three Ds)
 Protein synthesis is normal
 Treated by niacin supplements
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Digestion of carbohydrate using a diagram
if possible
 Absorption of carbohydrate using a
diagram if possible
 The effect of food preparation on
carbohydrate digestion and absorption
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Colonic fermentation of carbohydrate to
include types of carbohydrate reaching the
colon
 Physiological effects of carbohydrates not
digested in the small intestine
 Abnormal degradation of disaccharides
 Modification of fats during food processing
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Effect of heating on dietary oil
 Digestion of dietary lipids using a diagram
if possible
 Absorption of dietary lipids using a
diagram if possible
 Hormonal control of lipid digestion
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Defects if fat digestion and absorption
including causes and the nutritional
management of fat mal-assimilation
 Digestion of dietary proteins using a
diagram if possible
 Absorption of dietary proteins using a
diagram if possible
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Defects in protein digestion and absorption
 Coeliac disease
 Steatorrhea (definition – causes – dietary
management)
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