Drewes: Transporters in the GI System Flashcards
Transcellular route
across plasma membrane
paracellular route
across tight junctions (vary in permeability; impermeable to large organic molecules - AA and glucose)
What establishes electrochemical gradients?
Na/K/ATPase
What is used to move substances against their concentration gradient?
ATP
What is simple diffusion?
Compound diffusing DOWN its gradient b/c its LIPID SOLUBLE
What is facilitated diffusion?
Pores- channel
Gates- ligand binds> temporary pore
Transport molecules- help move other molecules across the membrane
What is endocytosis?
Part of the membrane buds off to allow entry into the cell
What transporter has 12 transmembrane segments and bindings sites where substrates bind and are carried to the other side of the membrane?
GLUTs
How many types of GLUTs are there?
13 types in 3 classes
GLUT4
insulin sensitive
GLUT1
RBC
How many segments make up MCTs? What do htey do?
12
carry lactate and beta hydroxybuterate in and out of cells
What are ATP binding cassette transporters?
Hydrolyze ATP to transport molecules across membrane
What transporters in the GI tract are involved w/ MDR and CFTR?
ATP binding cassette transporters
What are 3 transporters of the GI tract?
GLUTs
MCTs
ATPases
What is the single most important process in the SI to make absorption possible?
Electrochemical gradient of Na
LOW Na is maintated by Na/K/ATPases on basolateral membrane
Accumulation of Na outside cells is responsible for absorption of Water, AA and Carbs
How much water does the SI absorb daily?
9 L
Abosrption of water in the SI is dependent on?
Na co-transported w/ glucose and AA
How is water absorbed?
Transcellular and paracellular
Na gradient set up d/t uptake of Na>
water diffuses across membrane d/t osmotic gradient>
diffuses into blood
What enzymes at the brush border act on polysaccharides? What does this form?
Maltase
lactase
sucrase
Glucose and galactose which are then absorbed in the SI via a Na dependent transporter
SGLUT1
glucose and galactose
GLUT5
fructose
GLUT 2
transports glucose, galactose and fructose OUT of the enterocyte across basolateral membrane DOWN conc grad into capillaries
What enzymes are used for the digestion of proteins?
- Stomach> PEPSINOGEN> coverted by H to PEPSIN
- Pancreatic proteases: trypsin, chymotrypsin, carboxypeptidase
- SI peptidases- covert free AA at brush border
What is the difference between lumenal and basolateral AA transporters?
Lumenal- Na dependent AA transporters
Basolateral- NON- Na dependent AA transporters
How are di and tri-peptides absorbed?
Absorbed into the SI via cotransport w/ H ions>
once inside the enterocytes they’re digested by CYTOPLASMAIC PEPTIDASES
What is emulsification?
Bile acids (derivatives of cholesterol) have both hydrophilic and hydrophobic domains which intercalate into the lipid --> smaller droplets
What is hydrolysis?
Accomplished by PANCREATIC LIPASE which clips FAs at
positions 1 & 3 from triglyceride >
2 FAs and a 2-monoglyceride.
What is micelle formation?
liberated FAs and monoglycerides maintain
association with bile acids and complex with other lipids to form micelles. These micelles bump into the brush border and lipids are taken up into the cells.
How do FA and 2-MG enter enterocytes?
simple diffusion
Once insde the enterocyte, FA and MGs are transported to the ER to synthesize…
TGs
What are chylomicrons?
TG packaged w/ cholesterol, lipoproteins and other lipids into particles (by ER and golgi)
What happens to chylomicrons extruded from the Golgi?
Golgi>
exocytotic vesicles>
basolateral side of enterocyte>
exocytosis into lymphatic vessels
What is cholesterol homeostasis?
Balance of:
cholesterol synthesis
absorption of dietary cholesterol
elimination of cholesterol by excretion in the bile
Specific transport of nutrients and water occurs primarily in the…
jejunum
Active secondary transport usually occurs on the…
apical side
Carrier mediated transport usually occurs on the …
basolateral side
Active ABC-type transport usually occurs on…
both sides
What is the mechanism of acid secretion?
1) Hydrogen ions generated within parietal cell from dissociation of water. The hydroxyl ion combines with CO2 to form bicarbonate (catalyzed by CA)
2) Bicarb is transported out of the basolateral membrane in exchange for Cl-
3) Cl- and K+ ions are transported into the lumen of the stomach via conductance channels
4) H+ ions are pumped out of the cell in exchange for K+ through a proton pump
5) The accumulation of H+ sets up an osmotic gradient > outward diffusion of H2O
What are the 3 stimulators for acid secretion?
ACh
Gastrin
Histamine
ACh
(Muscarinic receptor)> increases intracellular Ca concentration
Gastrin
Increases intracellular Ca concentration
Histamine (H2 receptor)
Activates adenylate cyclase>
increases cAMP>
activates PKA>
phosphorylation of cytoskeletal proteins involved in transport of H/K/ATPase from cytoplasm to plasma membrane
Ca and bombesin stimulate…
gastrin release
PGE2, secretin, GIP, glucagon and somatostatin all decrease…
gastric acid secretion
What drug therapy is used for gastric acid secretion?
H2 receptor antagonists
PPIs
f a patient had an intolerance to proteins with high lysine and/or arginine and they excreted the amino acid in the stool (and/or urine) what may be the transporter defect.
That defect might be in a cationic amino acid transporter. You might also think about where the transporter is localized in the epithelial cell.
How are AA transporters distributed along the GI tract?
greatly varies!
How are lactate transporters distributed along the GI tract?
MCT1 is variably distributed but is OVEREXPRESSED in the COLON
What does MCT1 transport?
short carboxylic aicds
How do bacteria in the colon relate to hte MCT1 transporter?
Bacteria in the colon digest cellulose and things that haven’t been digested>
forms carboxylic acids>
bacteria produce butyrate>
MCT1 transfers butyrate across the lumen>
coloncytes use butyrate as fuel
Mutations in MCT1 is linked to what types of cancer?
colon cancer
What drug delivery issues are related to ABC transporters?
First barrier to noxious compounds (drugs)
Act as drug EFFLUX transporters by pumping noxious molecules back OUT into the lumen
*transporters are located on BOTH sides of hte epithelial cells
How does the transport of TG/lipids differ from that of most dietary nutrients?
Transported in chylomicrons into lymphatic vessels before entering the blood stream
What are the two main processes that establish an osmotic gradient that pulls water into the lumen?
- influx/digestion of foodstuffs> Increase in luminal osmotic pressure
- Crypt cells secrete electrolytes> water follows (ie. CFTR and cholera> Cl efflux and diarrhea)
