Cystic Fibrosis Flashcards
Structure of CFTR
2 trains membrane domains that form channels and allows for specificity.
- 2 glycosylation sites on the extracellular side.
- 2 nucleotide binding domains
- Regulatory domain “R” - there are 4 serine residues tha gets phosphorylated by cAMP and activates PKA.
Mechanism of action of CFTR
Once PKA is activated by R, ATP is able to support channel opening.
WHy do patients have more Cl- in their sweat?
Chloride channel defect in the sweat duct
WHy do CF patients have difficulty breathing?
Decreased Cl- secretion into the airways and increased Na+ and H2O reabsorption because of this. This decreases mucosa ciliary action because the mucous is very dry. This plugs up airways.
Why are many CF patients unable to digest foods properly?
CF affects the pancreas so amylase, proteases, lipases, and bile salts aren’t secreted properly.
How do you treat the pancreatic insufficiency in CGF patients?
Enteric coated capsules with pancreatic enzymes
What is the most common mutation. In the. CFTR. Gene?
Delta F508
What exactly Does delta508 cause?
Improper folding of CFTR. It prevents stabilizing interactions between NBD1 (nucleotide binding domain) and MSD1 (membrane spanning domain)
How do we treat CFTR if the protein was misfolded and due to a nonsense mutation?
- Only if due to a nonsense mutation you can induce a read-through of the stop codon which enables full-length protein to be synthesized.
- Gentamicin - can suppress premature termination codons.
- ataluren - does same thing
What are some small molecules that can help patients. With CF 508 mutation?
Corrector compounds such as VX-809 and VX-770 increase the amount of defective CFTR in the airway to try and increase Chloride transport.
- VX-770 (Kalydeco) is specifically good for patients with G551D mutations
What is CFTR?
Member of ABC transporter ATPase.
- it is the only ion channel within this family.
