Lecture 1

Question 1

Movement across membranes

Answer 1

Passive diffusion

Facilitated diffusion

Active transport

Secondary active transport

Question 2

Passive diffusion

Answer 2

Directly through membrane

Question 3

Facilitated diffusion

Answer 3

• Ion channels

* Uniporters

Question 4

Secondary active transport

Answer 4

• Co-transporters (symporters)

* Counter-transporters (antiporters)

Question 5

Active transport

Answer 5

Energy (ATP) required to transport a substance across a membrane against a concentration gradient

Question 6

Cystic Fibrosis Transmembrane conductance Regulator (CFTR)

Answer 6

anion-selective channel expressed mainly in the apical membrane of epithelial cells

Question 7

What happens when there is a defect with CFTR activity

Answer 7

Defects in CFTR activity lead to many forms of secretory diarrhoea as well as cystic fibrosis (CF), the most common, inherited, life-limiting, disease in white people

Question 8

What is Cystic Fibrosis?

Answer 8

CF is a disease of epithelial electrolyte transport and is caused by loss of function mutations in CFTR

Question 9

What happens to CFTR with CF?

Answer 9

CFTR is either absent or not active, so Cl- and therefore fluid secretion is impaired, leading to dehydrated secretions.

Question 10

What does the defect in CFTR cause in CF

Answer 10

This causes ducts to become blocked by thick sticky mucus, and in the lungs, predisposes to bacterial infections and eventually to lung failure

Question 11

What are the drugs for CF?

Answer 11

Lumacaftor

Ivacaftor

Question 12

What does Lumacaftor do?

Answer 12

Lumacaftor acts as a chaperone during protein folding and increases the number of CFTR proteins that are trafficked to the cell surface

Question 13

What does ivacaftor do?

Answer 13

Ivacaftor is a potentiators of CFTR that is already at the cell surface, increasing the probability that the defective channel will be open and allow chloride ions to pass through the channel pore

Question 14

cAMP signalling cascade

Answer 14

1. Signal molecule binds to G protein-linked receptor, which activates the G protein
2. G protein turns on adenylyl cyclase, an amplifier enzyme
3. Adenylyl cyclase converts ATP to cyclic AMP
4. cAMP activates protein kinase A
5. Protein kinase A phosphorylates other proteins. leading ultimately to a cellular response

Question 15

Dysregulation of fluid homeostasis - cholera

Answer 15

Cholera toxin inhibits absorption (from villi) and stimulates CFTR-mediated Cl- secretion (from crypts) via irreversible changes in cAMP/PKA in enterocytes

Question 16

Cholera toxin interferes with G-protein hydrolysis

Answer 16

ADP-ribosylation of Gα prevents hydrolysis of GTP

Locks G-protein in an active state

Adenylate cyclase constantly activated

Increase in cAMP leads to loss of Cl- and water into intestinal lumen

Severe watery diarrhoea -> dehydration -> death