Transcript Slides/AVS 504 Met Fri 2013 pt 2x

Protein Digestion and Peptide / Amino Acid Absorption
For the body to assimilate nutritional protein, it must first be broken down
into small peptide fragments and free amino acids.
- this occurs to a limited extent in the stomach
- the majority hydrolysis and absorption occurs in the small intestine
Digestion and absorption supplies circulating blood with a small amount of
bioactive peptides and a “pool” of amino acids.
In this absorptive state, amino acids are trans ported via portal blood to the liver
then on to subsequent organs and tissues.
Recommended Daily Allowances
RDA
57 kg Female 46 g/day
70 kg Male 57 g/day
31-50 y.o. Adult
Typical Ingestion
65 g/day
100 g/day
Endogenous proteins
The body digests an additional 50 – 100 g of endogenous
protein / day.
- Secreted or sloughed into the lumen of the
gastrointestinal tract.
- Saliva
- Gastric Juice
- Pancreatic Enzymes and other Secretions
- Sloughed Intestinal Cells
- Proteins that leak into the intestinal lumen
from the blood
Exogenous and endogenous protein
Approximately 115 – 200 g protein / day.
Only about 1.6 g Nitrogen (approx. 10 g protein) lost in fecal
mass
- endogenous protein or dietary protein not
absorbed in the intestine
- represented in the microflora mass in the
large intestine
Central Nervous System
Dietary Protein
Limited Gastric Hydrolysis
and Denaturation
HCl
Pepsin
Pancreatic Release of
Zymogens
CCK
Endogenous
Proteins
Digestion within
Intestinal lumen
Activated Pancreatic
Carboxypeptidases
Absorptive Enterocyte
Apical Membrane Transport
Enterocyte Apical
Membrane
Aminopeptidases
Selected Metabolism
within Enterocytes
AA Pool in Enterocyte
Cytosol
Basolateral Membrane
Transport
Portal Blood
Circulation
Protein Digestion in Phases
1. Gastric hydrolysis of peptide linkages in the protein
2. Digestion of protein to smaller peptides by action of
pancreatic proteases, which are secreted as zymogens
and activated in the lumen of the small intestine
3. Hydrolysis of peptide linkages in oligopeptides by brushborder (apical) membrane peptidases and transport of
amino acids and di- and tripeptides across the brushborder membrane of absorptive enterocytes
Protein Digestion in Phases
4. Further digestion of di- and tripeptides by cytoplasmic
peptidases in the enterocyte
5. Metabolism of amino acids within the enterocyte
6. Transport of amino acids across the basolateral
membrane of the enterocyte into the interstitial fluid
from which the amino acids enter the venous capillaries
and hence the portal blood
Pancreatic
Acinar Cell
Intestinal
Epithelial
Endocrine Cell
Zymogens released into
Intestine
Trypsinogen
Chymotrypsinogen
Proelastase
Procarboxypeptidase A
Procarboxypeptidase B
Vagus Nerve
Duodenal
Enterocyte
Enteropeptidases
(+)
Trypsin
(+)
Active enzymes in
Intestine
Chymotrypsin
Elastase
Carboxypeptidase A
Carboxypeptidase B
1. brush-border membrane peptidases
2. brush-border membrane amino acid
transporters
3. brush-border membrane di- and tripeptide
transporters
4. intracellular peptidases
5.basolateral-membrane amino acid carriers
6. basolateral membrane di- and tripeptide
carriers
Monomeric Amino Acid Transporters and Transport Systems in the Small Intestine
System
Name
A
Common
Name
SNAT2
B or Bo
BoAT1
Bo+
ATBo+
Y+
X-ag
IMINO
Iminoacid
CAT-1
EAAT3
SIT1
PAT1
GLY
T
Creatine
Pept1
GLYT1
TAT1
CRTR
PEPT1
Ion
Dependency
Na+
Substrate
Ala, Asn, Cys,
Glu, Gly, His
Met, Pro, Ser
neutral AAs
Na+
Glu
neutral and
Na+,Cldibasic Aas,
Arg, D-Ser
Arg, dibasic AAs
none
Glu, Arg
H+, Na+,K+
Pro, pipecolate
Na+
Pro, Gly, Ala,
H+
GABA, Tau, Ser
Glycine
Na+, Claromatic AAs,
none
Creatine
Na+, Cldi, tripeptides,
H+ with NHE3
Car, B-lactam,
antibiotics, Angiotensin
converting enzyme inhibitors
Location
Basolateral
Apical
Apical
Basolateral
Apical
Apical
Apical
Basolateral
Basolateral
Apical
Apical
Heterodimeric Amino Acid Transporters and Transport Systems in the Small Intestine
System
Name
asc
Common
Name
asc-1 plus
y+L
y+LAT plus
Arg, dibasic and
neutral AAs
x- c
xCT plus
Cys/Glu exchange none
Basolateral
L
LAT2 plus
BCAA, neutral AAs none
Basolateral
bo+
boA+T plus
dibasic AAs, Arg, none
Cys, large neutral
Aas, exchanges
extracellular dibasics
with intracellular
neutral AAS.
Apical
Substrate
neutral D,L-Aas,
Ala, D-Ser
Ion
Dependency
none
none (or Na+
for large Aas)
Location
Basolateral
Basolateral
Selected Bioactive Peptides Derived from Food
Source
Name
Physiological Activity
Meat
L-carnosine
Wheat
Wheat
Gliadorphin
Gluten exorphin-AS
Milk
Milk
Milk
Milk
B-lactorphin
B-casokinin -7
Caseoplatelin
Lacottransferrin
thrombic inhibitory
peptide
Lactoferricin
Phosphopeptide
antiinflammatory, antioxident,
prevents glycation
Opioid agonist
inhibition of stress induced pain,
CNS opioid agonist
ACE inhibitor
ACE inhibitor
inhibits platelet aggregation
inhibits platelet aggregation
Milk
Milk
antimicrobial
calcium/phosphate stabilizing
to enhance absorption
Paracellular uptake
Paracellular uptake occurs by movement
Of peptides between the mucosal cells
instead of through mucosal cells.
This occurs when tight junctions
between epithelial cells are damaged
and become “leaky”.
Leaky junctions increase non-specific
permeability of the intestinal epithelium
to all macromolecules.
Polypeptide uptake and transport
In the presence of healthy mucosa,
milligram amounts of of intact poly
peptides can be absorbed via
endocytotic uptake across the brushborder membrane and followed by
exocytosis across the basolateral
membrane.
Intact large peptides
1. IgA/M-cell presentation to Peyer’s Patches
2. Enterocyte endocytosis/lysosome/exocytosis
3. Paracellular movement across leaky junctions
Crypt of
Lieberkuhn
Lymphoid tissue
Immune response