1) When Regulation Goes Wrong (CTX & PTX) Flashcards
What 2 Toxins are being focused on?
Cholera toxin & Pertussis toxin
What pathogen secretes Cholera toxin CTX?
Vibrio Cholerae
What pathogen secretes Perstussis PTX?
Bordetella
Where does colonisation of CTX occur?
small intestine
What cells actively secrete electrolytes ?
Crypt cells , line intestinal epithelium
What is the receptor that allows passage of Cl- into intestinal lumen?
CFTR
What type of receptor do crypt cells activate ?
G-protein coupled receptors
What activates the CFTR ?
activation of adenyl cyclases and increases cAMP levels
What does increased Cl- in lumen create?
electrical potential, attracts Na+
How do Na+ travel into lumen? What kind of junctions?
tight junctions
Where does the NaCl accumulate?
Gastrial intestinal lumen
What is the result of NaCl in lumen?
creates an osmotic gradient across tight junction so water is drawn into gut lumen.
What subunits make CTX?
a-b type toxin 2 alpha (1&2) subs and 5 beta subs
What does the alpha 1 subunit do in the cell?
increases adenyl cyclase activity and increases cAMP
What does the CTX travel through
golgiac apparatus into lumen of endoplasmic rectilium
Effect of increased cAMP levels?
excessive secretion of Cl-, CO3- & H20
What catalyses the increased cAMP reaction?
Alpha 1 subunit
What does CTA1 catalyse?
ADP-ribosylation the Argentine residue present in the G-alpha-s protein
What is the source of the ADP-ribose?
NAD
What activates the allosteric CTA1 protein?
On one side; NAD-RNA-ribose
On the other; ARF6 (Co-activator)
What becomes cleaved on the CTA1 protein?
N-glycosidic bond of the Nicitinomide and ADP- ribiose
What occurs when the G-alpha-s is rybosylated?
the arg residue is irreversibly modified by addition of ADP-ribosyl group from NAD+
G-alpha-s can bind GTP but cannot hydrolyse it
increase cAMP.
What does PTX invade?
respiratory system
settle in bronchioles of or trachea
cilia stuck together my adhesion molecules
What subunits does PTX have?
1 alpha and 5 beta
What alpha subunit is involved in PTX?
G-alpha-i
What subunit binds to receptor on epithelial cells?
Beta
What subunits are endocytosed by receptor ?
the whole molecule
What is the fate of the alpha subunit in PTX?
transferred from golgi to ER, dissociates from pentamer, alpha transported to cytosol…
what the effect PTX alpha subunit on G-alpha-i ?
It RNA-ribosylates the G-alpha-i, locks into inactive state (GDP- bound form). Can’t inhibit adenyl cyclase, increase cAMP.
What is a way to describe G-alpha-protein complexes?
Heterotrimeric