Signaling Flashcards

1
Q

___________________ is a 51 amino acid peptide that is released by pancreatic beta cells of the islets of Langerhans when the concentration of blood glucose is high.

A

Insulin

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2
Q

______________________ is a 29 amino acid peptide hormone that is released when the concentration of glucose in the blood drops below 5 mM.

A

Glucagon

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3
Q

Where are receptors for glucagon located in the body?

A

In the liver and fat cells; there are no glucagon receptors on muscle cells

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4
Q

_______________________ is a catecholamine hormone that signals fight or flight; it is produced in the adrenal glands.

A

Epinephrine

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5
Q

Both _____________ and ____________ act upon G-protein coupled receptors.

A

Glucagon

Epinephrine

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6
Q

____________ ________________ ____________ _____________ are a key component of a signaling pathway - a pathway that transduces a signal that converts information (i.e., a hormonal signal) into a chemical change. Signal transduction pathways are characterized by having highly specific interacts between ligands and receptors in the nM kd range and amplified signals.

A

G-protein coupled receptors

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7
Q

What are the three essential components of G-protein coupled receptors?

A
  1. Plasma membrane receptor with 7 transmembrane helical segments
  2. An effector enzyme in the pasma membrane that generates an intracellular second messenger
  3. A guanine nucleotide binding protein (“G-protein”)
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8
Q

What are the seven steps of the GPCR stimulatory pathway?

A
  1. Ligand binds to receptor
  2. Occupied receptor causes replacement of the GDP bound to Gs by GTP, activating Gs
  3. Gs (alpha subunit) moves to adenylyl cyclase and activates it
  4. Adenylyl cyclase catalyzes the formation of cAMP
  5. cAMP activates PKA
  6. PKA phosphorylates cellular proteins that causes response to ligand
  7. cAMP is degraded, reversing the activation of PKA
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9
Q

What are three ways to stop a signal?

A
  1. Degrade secondary messenger (cAMP)
  2. Replace GTP with GDP on G-protein (intrinsic GTPase activity)
  3. Receptor endocytosis
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10
Q

What degrades the secondary messenger cAMP?

A

Cyclic nucleotide phosphodiesterase

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11
Q

______ _____________ is a heterotrimeric protein that consists of three subunits (alpha, beta, gamma). Upon hormone binding to receptor, GDP is replaced by GTP, activating the alpha subunit and releasing it from the beta-gamma complex. The alpha subunit moves in the membrane to an effector protein and activates it. This protein contains intrinsic GTPase activity that limits its time in the active GTP bound state.

A

G-protein

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12
Q

_____________ _______________ is an integral membrane protein that is activated by association with Gsalpha-GTP and catalyzes the formation of the secondary messenger, cAMP.

A

Adenylyl cyclase

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13
Q

___________ is a common secondary messenger, an intracelullar mediator of an extracellular hormonal signal.

A

cAMP

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14
Q

Adenylyl cyclase catalyzes the conversion of ATP to _____________, a 3’ –> 5’ cyclic structure.

A

Cyclic AMP

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15
Q

___________________ phosphorylates multiple targets at specific sites containing serine or threonin residues; it is inactive when its regulatory and catalytic subunits are bound together and active when cAMP binds its regulatory subunits, freeing its catalytic subunits.

A

Protein kinase A

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16
Q

In the liver, what is the net effect of glucagon signaling?

A

Increased blood glucose levels; therefore, gluconeogenesis should be on

17
Q

When glucagon binds its GPCR on a liver cell, what signaling pathway is stimulated?

A

PKA is activated; PKA phosphorylates PFK2/FBPase2, which activates the FBPase2 domain

When FBPase2 is activated, the concentration of fructose-2,6-bisphophate decreases, which activates FBPase1 and gluconeogenesis

18
Q

When glucagon binds its receptor in the liver, what is the effect on PFK-2/FBPase-2?

A

PFK-2/FBPase-2 is phosphorylated, which deactivates PFK-2 activity and activates FBPase-2 activity

19
Q

What happens to the concentration of fructose-2,6-bisphosphate when PFK-2/FBPase-2 is phosphorylated?

A

It decreases because FBPase-2 domain is active

20
Q

When PFK-2/FBPase-2 is phosphorylated, the concentration of fructose-2,6-bisphosphate decreases. What effect does this have on PFK-1?

A

PFK-1 is deactivated and glycolysis is inhibited

21
Q

When PFK-2/FBPase-2 is phosphorylated, the concentration of fructose-2,6-bisphosphate decreases. What effect does this have on FBPase-1?

A

FBPase-1 is activated and gluconeogenesis is stimulated

22
Q

When PKA is activated by the glucagon signal in the liver, two targets are phosphorylated: PFK-2/FBPase-2 and _______________ ______________.

A

Pyruvate kinase

23
Q

Phosphorylation of pyruvate kinase by PKA ___________________ the enzyme.

A

Inactivates

24
Q

Glucagon acts on both liver and ______ cells.

A

Fat

25
Q

In the liver, the effect of epinephrine is the same as that of glucagon; epinephrine can also act on muscle cells, but its effects are different there. Why?

A

In muscle, epinephrine stimulates the break down of glycogen; therefore glycolysis is operational

26
Q

Glucagon and epinephrine stimulate gluconeogenesis in the liver, but in the muscle cells, epinephrine stimulates what process?

A

Glycogenolysis

27
Q

What type of receptor is the insulin receptor?

A

A tyrosine kinase receptor (RTK)

28
Q

______________ __________________ __________________ function as binding sites for hormones on the extracellular face of the plasma membrane with enzymatic active sites on the cytoplasmic face; enzymatic activity is a protein kinase that phosphorlyates tyrosine residues in target proteins, and insulin receptor substrate (IRS-1) is phosphorylated upon insulin binding.

A

Receptor tyrosine kinase

29
Q

Insulin stimulates three major cellular responses. What are they?

A
  1. Movement of glucose transporters to the membrane
  2. Increase in the transcription rates of glycolytic enzymes (PK, glucokinase, PFK-1)
  3. Decrease in the transcription rates of gluconeogenesis enzymes (PEPCK, G6Pase, FBPase-1)
30
Q

What do glucose transporters facilitate?

A

The diffusion of glucose across the plasma membrane

31
Q

What glucose transporter is found in the liver and remains embedded within the plasma membrane?

A

GLUT2

32
Q

What glucose transporter is located in the brain and resides within the plasma membrane?

A

GLUT3

33
Q

What glucose transporte is found in cardiac and skeletal muscle tissues and adipose tissues and moves from intracellular vesicles to the plasma membrane upon insulin signaling?

A

GLUT4

34
Q

What is the net result of insulin signaling?

A

Increase in glycolytic flux

35
Q

How does insulin stimulate glycolytic flux?

A

Insulin binding results in phosphorylation of phosphoprotein phosphatase, which dephosphorylates PFK-2/FBPase-2; this activates PFK-2 and deactivates FBPase-2, leading to increased concentrations of F26BP; increased concentrations of F26BP stimulate the activity of PFK-1 and inhibit the activity of FBPase-1, thereby turning glycolysis on and gluconeogenesis off

36
Q
A