cAMP and PKA

Question 1

What is the role of Adenylyl cyclase (AC)?

What is the role of cAMP Phosphodiesterase (PDE)?

What are the roles of Gs and Gi in AC?

What is a direct pharmacological activator of AC? (Hint: Fat loss pills)

What are the three direct pharmacological regulators of phosphodiesterase?Follow-up question, which one is an adesoine receptor anatgonist? Which one is not used clincially? Which one is used to treat bronchodilator, that is similar to Albuterol, beta2 adrenegic recpeotr agonist?

Answer 1

Converts ATP to cAMP

Breakdown cAMP to AMP

They regulate the AC

Forskolin

Caffeine, IBMX, Theophylline

Question 2

Choose the best option

(Cholera toxins / Pertussis toxins)

Specific for alpha s

Inhibits GTPase activity by ADP ribosylation active site of GTPase

Make GTPase permanently inactive

Once activated by GPCR, alpha s remain permanently active

Stuck accelerator

Answer 2

Cholera toxins

Question 3

Choose the best option

(Cholera toxins / Pertussis toxins)

Specific for alpha i

Prevents activation of alpha i

Permanently preventing interactions with GPCRs

Alpha i remain in inactive form

Broken Brake

Answer 3

Pertussis toxin

Question 4

True or False

Both Cholera toxin and Pertussis toxin result in high levels of cAMPs

Answer 4

True

Question 5

Fill in the blank

_________ -nonhydrolysis analog of GTP bind to the G protein (either s or i) and lock them in an active state

_______ bind to the G protein (either s or i) and keeps them in an inactive state

Answer 5

GTP(gamma)S

GTP(beta)S

Question 6

How does cholera toxin induces diarrhea?

Fill in the blanks in the answer

Circle the correct answer in ( )

Toxins enter cells and catalyzes _____________ of G alpha (s/i) by tarnsferiing ADP-ribose from NAD to active site of GTPase

___________ are elevated in crypt epithelial cells, leads to hyperactivity of ______________.

High ___ and ____ in the intestinal lumen draws up to six liters of water per day into the lumen leading to the massive amount of diarrhea

It has been proposed that CF-causing mutation in CFTR confer _________ advantage against cholera.

Answer 6

Irreversible covalent modification

G alpha s

cAMP

CFTR Cl- channel

Na, Cl

heterozygote (it is a recessive recessive homozygous LOF mutation in CFTR)

Question 7

What is one advantage of multistep hierarchical signaling pathways?

Answer 7

The Transucduction and Ampliclication of the signal.

Question 8

Looking at the image which of these steps are stoichiometric and catalytic

Answer 8

Question 9

______ a protein in virtually all mammalian cells that are directly regulated by cAMP

Contain two regulatory subunits and inactive catalytic subunits

Answer 9

PKA

Question 10

True or False

The role of PKA catalyzes the transfer of the gamma phosphate group to the free hydroxyl group on the acid side chain Forms ester groups

Answer 10

True

Question 11

True or False

PKA is very specific to regret aa, highest activity against Ser and Thr within the sequence

PPXS/T or PXS/T

PKA consensus sequence

Answer 11

True

Question 12

What is the two way of Regulation of PKA?

Answer 12

Regulatory subunits bind to the catalytic subunits.

AKAP bind to R subunits of PKA

Question 13

The cAMP is a ____________ of the binding of the PKA regulatory subunit to the catalytic subunit.

Answer 13

negative allosteric modulatory

Question 14

Match the regulations that occur in this pathway

Your choices:

Ligand Binding

Covalent Modification

Binding of an activating protein

Unmasking

Translocation

Answer 14