Exam II-L10 Flashcards
How can we instruct the cell to change its behavior?
Cellular signaling or signal transduction pathway
True or False: Phosphorylation or dephosphorylation of a protein can activate or inhibit its catalytic activity
True
Ligand, GPCR, G-protein heterodimeric complex, effector proteins, 2 messenger, 2 messenger kinase, and activated kinase target are all components of what type of receptor?
GPCR receptor
What are the three domains of the GPCR?
1) Seven transmembrane helices
2) Extracellular domain - has binding site for ligand
3) Intracellular domain - interacts w/G proteins
What subunits make up the G protein heterodimeric complex?
G alpha, G beta, and G gamma
How is G alpha activated and inactivated?
Activation: GEF will replace GDP for GTP
Inactivation: GAP will replace GTP with GDP
Steps of GPCR activation?
1) Ligand binds
2) GDP is exchanged for GTP (GEF)
3) Ga subunit is activation and dissociates
4) Effector proteins are activated
5) Second messengers are generated
What subunits make up the Gs protein?
Gs = alpha, beta, gamma subunit + GDP
Once ligand binds to receptor, the receptor undergoes a _____ and interacts with Gs proteins. Ga releases GDP (binds GTP) and dissociates from beta and gamma subunits.
conformational change
True or False: Unoccupied GPCR receptors do not interact with Gs protein
True
Once alpha subunit of Gs protein dissociates from beta/gamma subunits, what effector protein does it activate?
Adenyl cyclase
(activation of adenyl cyclase converts ATP to cAMP and PPi)
High levels of cAMP activates ___
PKA
(PKA then goes on to phosphorylate a variety of target proteins)
How can you stop adenylyl cyclase signaling?
1) hydrolysis of Ga GTP
2) phosphodiesterase (converts cAMP to 5 AMP = cannot activate PKA)
3) Gai (inhibit adenylyl cyclase activity)
True or False: adenylyl cyclase converts ATP to cAMP and PPi
True
True or False: cAMP binds to the regulatory subunit of PKA, allow catalytic subunit of PKA to be activated and behave as a kinase
True
If you inhibit adenylyl cyclase, you also inhibit a downstream protein known as ___
PKA
What are the three different types of G proteins + their functions?
Gas: Stimulates adenylyl cyclase
Gai: Inhibits adenylyl cyclase
Gaq: Activates phospholipase C (effector enzyme)
What types of molecules are: IP3, DAG, and Ca2+?
Second messengers
What is the function of Phospholipase C, a membrane-bound enzyme?
Converts PIP2 to DAG + IP3
Release of what molecule is triggered by IP3?
Calcium
__ and ___ activate PKC in the pathway involving Phospholipase C (PLC)
Calcium and DAG
What is the role of phospholipase C in GPCR activation?
After ligand binds, activated receptor interacts with G protein, Gaq is activated and dissociates…
1) Phospholipase C (effector protein) is activated
2) IP3/DAG are made, leading to Calcium release
3) Calcium and DAG activate PKG
4) PKG phosphorylates target proteins
Which subunits activate PLC?
Gaq
____is a calcium binding protein that acts as a co-factor in many enzymatic reactions
Calmodulin
____is a disease characterized by hyperglycemia
Diabetes mellitus
___ is a catabolic hormone produced in the alpha cells of the pancreas that signals ‘fast state’
_____ is an anabolic hormone made in the beta cells of the pancreas
Glucagon: is a catabolic hormone produced in the alpha cells of the pancreas
Insulin: is an anabolic hormone made in the beta cells of the pancreas
What receptors are used by glucagon? Where are they located?
GPCR - in the liver
What three processes are stimulated by glucagon?
Gluconeogenesis (liver)
Lipolysis (adipose)
Glycogenolysis
Ketogenesis (liver)
___ is a glucose storage molecule that is mostly stored in the liver for systemic use
Glucagon is a glucose storage molecule that is mostly stored in the liver for systemic use
What three stimuli initiates secretion of glucagon?
1) low blood glucose
2) epinephrine
3) consumption of protein
True or False: Stress hormones stimulate gluconeogenesis, glycogenolysis, and lipolysis in the liver
True
Glycogenolysis is triggered by ____
glucagon
In glucagon signaling, Gas activates adenylyl cyclase, which converts ___ → ___
Elevated cAMP leads to activation of ___ →_____ and _____
ATP to cAMP
cAMP → PKA → PPK (phosphorylase kinase) → PPb (glycogen phosphorylase)
What is the function of PPb (glycogen phosphorylase) ?
Glycogen → Glucose
True or False: Glucagon signaling enhances gluconeogenesis and glycogenolysis
True
What type of receptors are used by insulin?
RTK
(liver, muscle, adipose tissue)
What molecule stimulates…
- glycogen synthesis
- fat storage
- GLUT4 (glucose transport into adipose/muscle)
Insulin !!
What molecule signals for the GLU4 transporter to come to cell surface?
Insulin
What tissues is GLUT4 present on?
Adipose and muscle
True or False: GLUT4 lowers blood glucose
True
In diabetes, less insulin results in less ____ into adipose and muscle tissue and, thus, sustained higher blood glucose levels
glucose transport
What molecule stimulates glycogenesis and protein synthesis in muscle tissue and TAG synthesis in adipose tissue?
Insulin
Which molecule inhibits gluconeogenesis and ketogenesis in the liver, as well as lipolysis in adipose tissue?
Insulin
Cholera toxin permanently activates what two effector proteins? Effect?
Gas and AC
Effect: hyperactivation of CFTR, electrolyte and water efflux
How does pertussis toxin take effect to cause whopping cough?
1) Pertussis ribosylates Gai
2) G protein complex cannot interact with GPCR
3) AC cannot be turned off in lung epithelia
4) Whooping cough
What is the function of adenylyl cyclase?
Converts ATP to cAMP and PPi
