GIS23 Absorption Along GI Tract: Membrane Transport Flashcards
Functions of surface of GI tract
- Mucus layer demarcates a ***stable region to establish a chemical environment (e.g. pH, ionic strength)
—> free from interference
—> needed for digestion and absorption - Allow ***crosstalk to nervous system
- Epithelial cell surface provide ***large SA for controllable absorption
- ***Guarding against foreign pathogens
Basic driving force to transport solutes across biological membrane
- Tendency to achieve ***lowest Gibbs free energy (rule of nature)
- achieve quantitative and vectorial transport of metabolites
However,
1. Not all solutes will be transported to another compartment
- Additional ***activation energy is likely to be required to enable solute to cross the barrier
—> arise from loss of hydration of solutes as they cross the membrane - No guarantee that solute will always exist in the luminal compartments of GI tract at a concentration that is ***higher than that found within the enterocytes
Why transport proteins are necessary
- provide a molecular channel with an internal surface able to **interact favourably with the solute
—> energy cost of moving across cell membrane can therefore be reduced to a **minimum
—> ***lower activation energy in presence of transporter mediation
—> rate of mediated transport = JmaxC1 / Km + C1 (J: rate)
Facilitated transport
- Net transport cease when solute concentration in lumen equalises with that of cell interior
- problems:
1. Solutes may **leak out into lumen when interior concentration higher
2. Fluctuating solute concentration results in **fluctuating rate of in-cell transport of solutes
Active transporter
- Movement of solutes is not spontaneous
- need a **driver solute (any suitable molecular species, **ΔG2 to accompany: 要夠負)
- ΔG1 + ΔG2 < 0 —> movement across cell membrane will be spontaneous
- active transporter couple the energy changes of the two solutes via a series of molecular conformational changes of itself
- Symport / Antiport
- need to create a ***gradient of driver solute
- e.g. Na/K ATPase (electrogenic transport —> create charge difference)
—> ***Driver solute: Na
Transport of glucose in GI tract
Apical membrane of enterocyte:
1. SGLT-mediated transport (**Secondary active transport)
—> **SGLT1 (symport)
—> movement of Na into cell
—> movement of glucose (design of oral rehydration therapy)
Basolateral membrane of enterocyte:
1. Glucose move out of basolateral membrane through ***GLUT2 based on concentration gradient (high in cell, low in capillary)
- Na/K-ATPase —> pump Na out of cell
—> maintain ***low Na conc within cell
—> maintain Na concentration gradient across apical membrane
—> keep glucose transport into cell
Adapting to high glucose input from diet
SGLT1 (high affinity, low capacity) can also act as messenger to instruct more GLUT2 vesicles to be inserted onto ***apical membrane (原本只在basolateral)
—> GLUT2 (low affinity, high capacity): facilitated transport to help move large amount of glucose into enterocyte
Regulation of glucose metabolism by SGLT3
SGLT3 act as messenger to **instruct metabolism
—> send signals enteroendocrine cells
—> release **GLP1
—> stimulates pancreatic ***insulin secretion
Absorption of amino acids
Apical membrane:
- like glucose it has co-transporter to transport ***driver solute (Na) and amino acids into enterocyte
Basolateral membrane:
- only has TAT1 that do not need Na (transport aromatic a.a)
- others need Na to move a.a. in Symport manner (but [Na] in cell always low —> believed to only play role in starvation which move a.a. back into cell from blood along with Na)
- **Obligatory exchangers also do 1:1 a.a. exchange
—> postulated mechanism: a **Unidirectional transporter help recycling
—> exchanged a.a. from capillary will be transported out of the cell again by unidirectional transporter
—> continuously drive the obligatory exchanger to move other a.a. out of cell
E.g.
- 4F2hc/LAT2 obligatory transporter at Basolateral membrane utilises effluxed neutral a.a. from unknown transporter to mediate efflux of other neutral a.a.
(neutral a.a. is transported into the cell from apical membrane by PAT1 and BAT1 transporter which use H and Na as driver solutes respectively)
- Effluxed neutral a.a. can also be used to drive cationic a.a. out of cell by 4F2hc/y+LAT1 transporter
- Transporter that help basolateral efflux of **anionic a.a. is **unknown
Absorption of fatty acid
- TAG —(lipase)—> fatty acids + glycerol + MAG + DAG
- Long/medium carbon chain length fatty acids:
—> FA in micelle form due to hydrophobicity
—> bind to **FABPpm (a peripheral membrane protein on surface of enterocyte)
—> incorporation of FA molecule into the luminal leaflet of plasma membrane
—> specific fatty acid transporter **CD36 facilitates a flip action of FA molecule into the cell (180 degree change in orientation)
—> FA carried away by ***intracellular FA binding protein / converted to acyl-CoA
—> maintain a concentration gradient
—> continuous flow of FA from GI lumen - Short carbon chain length FA:
—> absorbed through mediation of transporters ***MCT (co-transport of H and FA) - Glycerol / MAG / DAG:
—> absorbed by transporter mediated processes - Cholesterol:
—> can be transported into/out of cell —> cholesterol homeostasis
Coupling between digestion, absorption and metabolism of dietary carbohydrates
Polysaccharide —> Oligosaccharide —> Disaccharide —> Monosaccharide
- Glucose
- SGLT1
- GLUT2 - Galactose
- SGLT1
- GLUT2 - Fructose
- GLUT5
Coupling between digestion, absorption and metabolism of dietary proteins
Protein —> oligopeptide —> amino acids (luminal side)
- Proteins
- ***paracellular absorption - Oligopeptide
- PEPT1 (co-transport with H) —> function as a **signaling system for secretion of **GI hormones
- exported as peptides / a.a. at basolateral side - Amino acids
- transporter mediated absorption
Summary
- Driving force: Concentration gradient generated with Na, H (i.e. driver solute) —> energy for generation of concentration gradient: ATP
-
**Several functions of transporter:
—> reduce energy requirement by reducing **unfavourable interaction between solutes and hydrophobic intramembrane environment
—> direct energy of ionic gradient to drive **uphill transport of solutes into enterocytes (SGLT1)
—> couple absorption and **metabolism of solutes (SGLT3 signaling)
—> adjust rate of absorption with nutrient requirement by changing level of ***molecular expression of these transporter (GLUT2: low affinity, high capacity) - Absorption of glucose:
—> SGLT1 protein: uphill transport driven by Na gradient - Absorption of a.a.: 2 types of a.a. transporter:
—> Unidirectional transporter + Obligatory exchanger - Absorption of lipid:
—> specific transporter protein, does not require an ionic gradient, gradient is ***generated by lipid itself (once migrated across membrane —> immediately removed from membrane)
