endo

Recap

1. ligand binds to GPCR
2. if ligand is an agonist it activates the GPCR
3. GPCR is able to talk to intracellular G-proteins
4. G-protein becomes activated- this can be detected becasue alpha-subunit had GTP bound. also alpha-subunit dissociates with BY-subunit
5. alpha-subunit is a GTPase and therefore kicks off a phosphate to produce GDP. therefore, reassocuition of aby

adenylate cyclase

• adenylate cyclase is a membrane bound protein - but essentially works as an enzymes
• it coverts adenosine triphosphate (ATP) to clyclic adenosine monophosphate (cAMP)
• in mammals, there are 10 different types of adenylate cyclass known

regulation of adenylate cyclase

physiological regualtion

• G-alphas (stimulatory) are able to activate AC
• G-alphai (inhibitory) inhibits AC activation

experimental regulation:

1. forskolin (a labdane diterpene produced in the indian coleus plant) activates AC
2. chlorea toxin causes ADP ribosylation of G-alphas- therefore alpha unit unable to associate with BY = ^ AC activity
3. pertussis toxin inhibits Gi so it remains in its inactive form (GDP) bound = ^AC activity

cAMP

• CAMP CAN ACTIVATE : PROTEIN KINASE A (PKA)
• as well as:cyclic-nucleotide gated ion channels
• exchange proteins activated by cAMP (EPACS)

cAMP decomposition:

1. phosphodiesterase inhibitors
2. bucladensine

Protein Kinase A (PKA)

• holoenzyme contains 4 subunits:
• 2 regulatory subunits
• 2 catalytic subunits
• …