GI 3 Flashcards
What is the small intesting higly adapted for
The small intestine is
highly adapted for digestion & absorption
What are the adaptations that the small intestine has that increases absorption and how do they work
- Plicae (folds)
Increase surface area - Intestinal epithelium is only 1 cell thick
Presents a minimal barrier to the transfer of molecules from the lumen to the circulatory system
- The enterocytes (epithelial cells responsible for digestion and absorption) express enzymes
These enzymes convert non-absorbable macromolecules to absorbable small molecules
What are incorporated into the plicae to increase surface area further
Plicae are covered with finger-like projections called villi (1 mm)
These villi are, in turn, lined with epithelial cells possessing microscopic projections - microvilli
All these adaptations lead to the small intestine having the equivalent surface area to a tennis court
Carbohydrate digestion:
Which GI enzymes are used to breakdown sucrose, lactose and maltose and what are the products formed
Sucrase catalyses the conversion of sucrose => glucose + fructose
Lactase catalyses the conversion of lactose => glucose + galactose
Maltase catalyses the conversion of maltose => glucose + glucose
Which transporter moves glucose and galactose into the enterocyte and what is required for this transporter to function
The SGLT1 transporter
This transporter is Na+-dependent meaning sodium ions are required to transport glucose. A sodium ion will also bing to the transporter along a chemical gradient and facilitate glucoses uptake into the cell
Which transporter moves fructose and galactose into the enterocyte and what is required for this transporter to function
Fructose is transported into the enterocyte by GLUT5
This transporter is Na+-independent meaning it doesnt need sodium ions to function
What do transporters in the basolateral membrane do
They transport substrates out of the cell and into the blood
How do we digest proteins
Proteins are digested into small peptides & amino acids
Which transporter moves small peptides into the enterocyte and what is required for this transporter to function
Small peptides are transported by PepT1 transporter which is
H+-dependent (has a similar principle as SGLT1)
What is the problem with hydrophilic drugs
Hydrophilic drugs do not readily enter plasma membrane leading to low drug bioavailability
How do drug designers exploit the high expression of transporters in the gut lumen
Absorption via GI uptake transporters is extremely efficient
This has been exploited by drug designers who formulate drugs based on natural products, e.g. peptide-based drugs (substrates for the PepT1)
Give 4 examples of drugs which are PepT1 substrates
> Enalapril
α-Methlydopa-phenylalanine
Penicillins
Cephalosporins, e.g. cefadroxil
What is the important feature of peptide like drugs which enables them to be taken up by transporters
They posess a peptide bond (which is recognised by the transporter)
Give an example of another important GI transporter which is used by drug designers
The OCTN2 - Organic cation transporter
Mechanism: antiporter/exchanger - as a drug enters the cell, a cation leaves
Substrates:
Quinidine, verapamil, imatinib, valproic acid
α-Methlydopa-phenylalanine, valacyclovir
OATP2B1 (Organic anion transporting polypeptide) is another clinically importent drug transporter. What are its substrates
Substrates: Pravastatin Rosuvastatin Atorvastatin Fexofenadine
