Class 13: Cholera-kincaid Flashcards
How do people get cholera?
Contaminated water
Fecal-oral route
Cholera caused by:
Vibrio cholerae. Fecal-oral route.
Shellfish are natural reservoirs.
Mechanism of induction:
Organisms adhere to intestinal mucosa of small intestine and secrete the toxin choleragen.
Results of cholera:
Presence of toxin results in massive loss of water and electrolytes.
-production of rice-water stool.
Choleragen:
A=activity-1 copy
B=binding-5 copies
Oligomeric: AB toxin
Disulfide bonds
Cholera toxin
Mechanism of cell entrance:
Has to bind to cell and gain entry. It becomes endocytosed. And forms lipid raft. Retrograde to cell golgi. Then goes to the ER. The disulfide bond.
B/c of the disulfide bond the ER chaperons believe the protein is misfolded. Polyubiquitinated to be degraded. Unable to be degraded by proteosome.
CFTR is phosphorylated by:
PKA
CFTR is an:
Ion channel controlling flow of Cl-
Cholera toxin:
(G protein) GTP cant be hydrolyzed - constantly ACTIVATED.
More cAMP-> PKA-> activated CFTR->constant flow of ions out of cell. Water follows the ion flow out of cell.
Main issue w/ cholera:
Massive loss of water and electrolytes.
Production of “rice-water stools”
Bluish tinge to skin.
Diagnosis of cholera:
Tx:
Culture from feces
Oral Rehydration and antibiotic therapy.
Vaccination for cholera:
Not very effective
CFTR:
12 Membrane-spanning domain Channel protein that transports Cl- in and out of cells and produce mucus, sweat, digestive enzymes.
Also, regulates function of other channels (NA+)
ABC transporter-essentially facilitated diffusion through a pore. Only use ATP to open the gate
Req’s ATP hydrolysis and phosphorylation.
CFTR mutations:
> 1300 categorized into 4 classes:
- Class I=defective protein product product w/ total loss of function
- Class 2=defective protein processing leading to CFTR not in the correct location or different from normal CFTR ~70% of CF patients (F508-ERAD)
- Class 3= defective regulation of channel opening of CFTR.
- Class 4= defective ion conduction.
Defective protein w/ total loss of function-CFTR
Class I mutation