Class 13: Cholera-kincaid

Question 1

How do people get cholera?

Answer 1

Contaminated water

Fecal-oral route

Question 2

Cholera caused by:

Answer 2

Vibrio cholerae. Fecal-oral route.

Shellfish are natural reservoirs.

Question 3

Mechanism of induction:

Answer 3

Organisms adhere to intestinal mucosa of small intestine and secrete the toxin choleragen.

Question 4

Results of cholera:

Answer 4

Presence of toxin results in massive loss of water and electrolytes.
-production of rice-water stool.

Question 5

Choleragen:

A=activity-1 copy
B=binding-5 copies

Oligomeric: AB toxin

Disulfide bonds

Answer 5

Cholera toxin

Question 6

Mechanism of cell entrance:

Answer 6

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.

Question 7

CFTR is phosphorylated by:

Answer 7

PKA

Question 8

CFTR is an:

Answer 8

Ion channel controlling flow of Cl-

Question 9

Cholera toxin:

Answer 9

(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.

Question 10

Main issue w/ cholera:

Answer 10

Massive loss of water and electrolytes.
Production of “rice-water stools”
Bluish tinge to skin.

Question 11

Diagnosis of cholera:

Tx:

Answer 11

Culture from feces

Oral Rehydration and antibiotic therapy.

Question 12

Vaccination for cholera:

Answer 12

Not very effective

Question 13

CFTR:

Answer 13

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.

Question 14

CFTR mutations:

Answer 14

> 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.

Question 15

Defective protein w/ total loss of function-CFTR

Answer 15

Class I mutation

Question 16

Defective protein processing leading to CFTR not in correct location to different from normal CFTR-most common

Answer 16

Class 2 mutation

Question 17

Defective regulation of channel opening-CFTR

Answer 17

Class 3 mutation

Question 18

Defective ion conduction-CFTR

Answer 18

Class IV mutation

Question 19

Autosomal recessive disorder

> 1300 mutaiton in CF gene

> 10 million white americans are asymptomatic carriers

Answer 19

Genetics of Cystic fibrosis

Question 20

Symptoms of CF

Answer 20

• Salty-tasting skin
• persistent coughing
• wheezing/shortness of breath-viscous mucous-Prone to bacterial infections
• excessive appetite, but poor weight gain
• greasy, bulky stool

Question 21

Connect mutaiton in CFTR and connect to ion flow

Answer 21

.

Question 22

Why is incidence of CF in northern europeans and descendants:

Answer 22

Decreased risk of obtaining cholera.

Selective advantage over cholera.