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BAPs - Coggle Diagram
BAPs
Pept1
Member of the H+-dependent
carrier family
, drives nutrients from the intestinal lumen into cells using the H+ electrochemical
gradient
PepT1 has 12 transmembrane regions (TMs)
and was first cloned from the intestines of rabbits
Knockout of the gene encoding PepT1 reduces dipeptide transport in the mouse intestine after gastric gavage (by 50%) and
oral administration (by 80%)
PepT1 deficiency in mammals mammals impairs causes malabsorption
becomes visible on high protein and high fat feeding
PepT1 can transport various small BAPs
Gly-Sar (glycyl-sarcosine, a hydrolysis-resistant
model peptide), GP, IRW...
It can only transport di- and tripeptides
Strategies to improve the bioavailability of BAPs
Enzyme inhibitions
can suppress the hydrolysis of peptides in the GIT
Permeation enhancers
Combining permeation enhancers with peptidase inhibitors is a
feasible solution to improve the bioavailability of BAP
Over 250 permeation enhancers have been used to improve the intestinal delivery of peptides by overcoming poor permeation caused by the physical and biochemical barrier of the GIT
Nano particles
Lipid based nanocarriers
Microparticles
Microencapsulation
Passive paracellular route
The surface area of the human gut has been estimated to be approximately 200 m2 (
The paracellular
diffusion area is thought to be approximately 0.02 m
is mediated by tight junctions (TJs) that
mainly consist of
zonula occludens-1, occludin, and claudin proteins
creates a tight biological barrier with selective penetration
A variety of BAPs can be transported by
energy-independent passive diffusion via paracellular TJs
passive route to transport oligopeptide
influenced by peptide properties and tends
to transport low molecular weight peptides that are water-soluble
Transport via the paracellular route enables peptides to avoid degradation by intracellular peptidases
. The permeability of fish collagen peptides across
Caco-2 cell monolayers is size-dependent
suggesting that the transport
of these peptides occurs mainly via the paracellular route
Peptide transport by transcytosis
An energy-dependent transcellular transport route that includes apical endocytic uptake into cells, transcytotic transport
via internalized vesicles and basolateral diffusion
the main pathway for transport of long-chain and certain other peptides
Bradykinin
(RPPGFSPFR)
VLPVPQK and
YPFPG
YFCLT and GLLLPH
Most of the BPAs that are transported via this route have highly hydrophobicity
The transcytosis route tends to favor hydrophobic peptides because, they need to interact with the apical lipid membrane
surface of epithelial cells through hydrophobic interaction before being
internalized by the cells
Endocytosis is a route to bind peptides
(usually large polar peptides)
to the cellular membrane and transport
them through the cell via vesiculation
Can be used as therapeutic agents
Food aditives
Pharmaceutical ingredients
Protein degradation and the fate of digestion products in the
GIT
1st step of protein breakdown is facilotated by pepsin hydrolysis in the acid enviroment of the stomach
Most peptides released from proteins pass into the intestine
Vital role in nutrients absorption
GIT
Food proteins can be digested into enormous numbers of aminoacids (AAs) and peptides by various digestive enzymes and microbial fermentation
Various biological activities of this peptides containing 2-20 AAs
antihypertensive, antimicrobial, anti-inflammatory, antithrombotic, antioxidative, antidiabetic, anticancer, antimicrobial, antiadhesive, dipeptidyl-peptidase IV-inhibitory, opioid,
Some BPAs can be created in the GIT
During protein digestion
Microbial or digestive enzymes
Trypsin
Pepsin
Chymotrypsin
Pepetides produced in the intenstinal Lumen
Are transported across the epitelial cell monolayer into the bloodstream
Routes
Carrier mediated permation
Paracellular transport
Transcytosis
Passive transcellular difussion
Human and animals studies
Majority of studies investigating the bioavailability of BAPs
have used in vitro cell models
there is still a lack of ex vivo or
in vivo experiments to determine the effects
bioavailability, plasma
concentrations, and pharmacokinetics of BAPs
Although studies in humans, rats (including spontaneously hypertensive rats, SHRs), and pigs provide evidence that these peptides
are absorbed in vivo
Factors regulating the bioviability of BPAs
The intestinal transport of BAPs is influenced by various peptide
properties
Size
Demonstrates that short-chain peptides (with higher Papp
values) are absorbed from the GIT more easily and efficiently
BAPs with small molecular weights have higher intestinal
permeability rates than those with high molecular weights
Molecular weight
Charge
Peptides with neutral AA residues are preferentially recognized by
PepT1
. PepT1 has a higher affinity for neutral dipeptides than
charged dipeptides
Hydrophobicity
AA composition
Might affect their bioavailability
The C- and N-termini of dipeptides are essential for binding
to the PepT1 pocket
It was reported that charged AAs, in the C-terminus contribute to bioavailability more than hydrophobic AAs
Side chain flexibility
Various BAPs can be transported across the intestinal
epithelial membrane in an intact or active form via PepT1
Large, hydrophobic, positively charged peptides tend to be transported
via transcytosis
Bibliografía
Xu, Q., Hong, H., Wu, J., & Yan, X. (2019). Bioavailability of bioactive peptides derived from food proteins across the intestinal epithelial membrane: A review. Trends in Food Science & Technology, 86, 399–411.
https://doi.org/10.1016/j.tifs.2019.02.050
Rebeca G Morán Farías A01283510