Gastrointestinal physiology lecture 3

Question 1

Sucrase metabolises…

Answer 1

Sucrose→glucose+fructose

Question 2

Lactase metabolises

Answer 2

Lactose→glucose+galactose

Question 3

Maltase metabolises

Answer 3

Maltose→glucose+glucose

Question 4

Adaptations of GIT

Answer 4

• Adaptations: plicae (folds) increase the surface area.
• The plicae are covered with finger like projections (vili-1mm) which increase surface area even more.
• The villi are lined with epithelial cells possessing microscopic projections – microvilli.
• The epithelium is 1 cell thick so short diffusion pathway.
• Large surface area and short diffusion pathway make digestion easy. 1 cell thick is the minimum barrier to transfer of molecules from lumen to capillaries and lacteals.
• 90% of the vilus are enterocytes which are involved in digestion.
• 10% are goblet cells that produce mucus and the others are endocrine cells.
• Massive blood supply to the small intestine

Question 5

How are glucose and galactose transported into enterocytes? What is this dependent on?

Answer 5

Glucose and galactose are transported into enterocytes by the SGLT1 transporter. It’s Na dependent.

Question 6

Can glucose permeate the membrane (enterocyte)

Answer 6

Glucose can’t penetrate the membrane unless it’s in high concentrations in the lumen.
Glucose sodium cotransporter.

Question 7

How is fructose transported?

Answer 7

Fructose is transported by GLUT5 and it’s independent of sodium.

Question 8

How are monosaccharides transported out of enterocytes?

Answer 8

Monosaccharides – transported out of the enterocytes by transporters in the basolateral membranes.

Question 9

How are large proteins broken down in the GIT?

Answer 9

large proteins are broken down into small peptides and amino acids.

Question 10

How are small peptides transported in the GIT? Is it dependent on anything?

Answer 10

Small peptides are transported by PEPT1 transporter and it’s proton dependent.

Question 11

How are amino acids transported in the GIT?

Answer 11

Amino acids are transported by several different systems (we don’t need to learn them all). Some transporters are sodium dependent instead of proton dependent.

Question 12

What kind of drugs don’t enter the lipid plasma membrane?

Answer 12

Generally polar, charged, hydrophilic molecules don’t enter the lipid plasma membrane. If this is the case the bioavailability is crap.

Question 13

When is drug absorption across the GIT good?

How has this been used to design drugs?

Answer 13

Absorption by uptake transporters is really efficient.
This has been exploited by drug designers to create drugs based on natural molecules such as peptide drugs being taken up by PEPT1.

Question 14

PEPT1 takes in what drugs?

Answer 14

PEPT1 takes in

• cephlasporins
• penicillins
• enalapril
• val-acyclovir
• methlydopa-phenyl alanine

Question 15

What drugs are taken in by the OCTN2 transporter?

Answer 15

• verapamil
• quinidine
• imatinib
• valporic acid
• val-acyclovir
• methlydopa-phenyl alanine.

Question 16

What drugs are taken in by OATP2B1?

Answer 16

• statins (PAR)

- fexofenidine.

Question 17

How can transporters can be detrimental to drug absorption?

Answer 17

Drug efflux transporters which have the opposite action of uptake transporters.
Drugs enter enterocytes and are actively pumped into the gut lumen by efflux transporters. This makes drug absorption bad.
-BCRP – pumps anticancer drugs out of breast cancer cells.
Intestinal P-gp and BCRP. They prevent drugs get into the blood so they are given IV. This leads to cytotoxicity.

Question 18

Where are the efflux transporters?

Answer 18

Epithelial cells have them

Question 19

P-gp substrates

Answer 19

HIV PI’s, immunosuppressants, antibiotics, cardiotonics.

Question 20

Why is it better to take Extravastation orally?

Answer 20

Extravasation – out of the vessels into the surrounding tissue causing necrosis. This is why it’s better to take it orally. In the case of extravasation you only get localised necrosis at the injection site. The only reason you don’t get systemic necrosis is because at the site of injection, it’s at it’s most concentrated, but by the time it travels far it becomes diluted.

Question 21

More bad sides to the transporters?

Answer 21

But there’s efflux transporters in the small intestine so patients are given modulators to inhibit the efflux transporters function. But the result is more systemic toxicity as you’ve got more drug in the blood.
But sometimes you have P-gp drug-drug interactions