1) When Regulation Goes Wrong (CTX & PTX) Flashcards

1
Q

What 2 Toxins are being focused on?

A

Cholera toxin & Pertussis toxin

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2
Q

What pathogen secretes Cholera toxin CTX?

A

Vibrio Cholerae

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3
Q

What pathogen secretes Perstussis PTX?

A

Bordetella

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4
Q

Where does colonisation of CTX occur?

A

small intestine

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5
Q

What cells actively secrete electrolytes ?

A

Crypt cells , line intestinal epithelium

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6
Q

What is the receptor that allows passage of Cl- into intestinal lumen?

A

CFTR

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7
Q

What type of receptor do crypt cells activate ?

A

G-protein coupled receptors

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8
Q

What activates the CFTR ?

A

activation of adenyl cyclases and increases cAMP levels

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9
Q

What does increased Cl- in lumen create?

A

electrical potential, attracts Na+

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10
Q

How do Na+ travel into lumen? What kind of junctions?

A

tight junctions

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11
Q

Where does the NaCl accumulate?

A

Gastrial intestinal lumen

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12
Q

What is the result of NaCl in lumen?

A

creates an osmotic gradient across tight junction so water is drawn into gut lumen.

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13
Q

What subunits make CTX?

A
a-b type toxin
2 alpha (1&2) subs and 5 beta subs
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14
Q

What does the alpha 1 subunit do in the cell?

A

increases adenyl cyclase activity and increases cAMP

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15
Q

What does the CTX travel through

A

golgiac apparatus into lumen of endoplasmic rectilium

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16
Q

Effect of increased cAMP levels?

A

excessive secretion of Cl-, CO3- & H20

17
Q

What catalyses the increased cAMP reaction?

A

Alpha 1 subunit

18
Q

What does CTA1 catalyse?

A

ADP-ribosylation the Argentine residue present in the G-alpha-s protein

19
Q

What is the source of the ADP-ribose?

A

NAD

20
Q

What activates the allosteric CTA1 protein?

A

On one side; NAD-RNA-ribose

On the other; ARF6 (Co-activator)

21
Q

What becomes cleaved on the CTA1 protein?

A

N-glycosidic bond of the Nicitinomide and ADP- ribiose

22
Q

What occurs when the G-alpha-s is rybosylated?

A

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.

23
Q

What does PTX invade?

A

respiratory system
settle in bronchioles of or trachea
cilia stuck together my adhesion molecules

24
Q

What subunits does PTX have?

A

1 alpha and 5 beta

25
Q

What alpha subunit is involved in PTX?

A

G-alpha-i

26
Q

What subunit binds to receptor on epithelial cells?

A

Beta

27
Q

What subunits are endocytosed by receptor ?

A

the whole molecule

28
Q

What is the fate of the alpha subunit in PTX?

A

transferred from golgi to ER, dissociates from pentamer, alpha transported to cytosol…

29
Q

what the effect PTX alpha subunit on G-alpha-i ?

A

It RNA-ribosylates the G-alpha-i, locks into inactive state (GDP- bound form). Can’t inhibit adenyl cyclase, increase cAMP.

30
Q

What is a way to describe G-alpha-protein complexes?

A

Heterotrimeric