cell signaling Flashcards

(41 cards)

1
Q

Type of signaling

A

regulatory signals that originate from conditions within the cell.
communication signals that occur between two neighboring cells.
Response to extracellular regulatory signals that are generated to coordinate metabolic activities and other activities essential for the development and survival of organisms.

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2
Q

model for initiating a cellular response to an extracellular signal

A
  1. Unoccupied receptor does not interact with G(s) protein.
  2. Occupied receptor changes shape and interacts with G(s) protein. G(s) protein releases GDP and binds GTP.
  3. Alpha subunit of G(s) protein dissociates and activates adenylyl cyclase
  4. When hormone is no longer present, the receptor reverts to resting state. GTP on the alpha subunit is hydrolyzed to GDP, and adenylyl cyclase is deactivated
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3
Q

What is an important receptor in pharmacology?

A

G-protein coupled receptors

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4
Q

G-protein coupled receptors

A

a family of integral membrane cell surface receptors

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5
Q

What are G-proteins characterized by?

A
  1. an extracellular ligand-binding domain
  2. seven transmembrane spanning domains
  3. a cytosolic G-protein activation domain
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6
Q

G-protein coupled receptors and ligands

A

bind to specific ligand. conformational changes due to ligand binding are transmitted to the interior of the cell.

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7
Q

Beta and Gamma subunits of the G-protein

A

act as membrane localizes docking site for the inactive alpha subunit. anchor for alpha

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8
Q

alpha subunit

A
  1. binds guanosine nucleotides (GTP/GDP)

1. the inherent ability to hydrolyze GTP to GDP, this is what turns it off.

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9
Q

depending on its activation state, the alpha subunit can interact with..

A

a specific activated GPCR or adenylyl cyclase

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10
Q

What determines if a g-protein functions to stimulate (Gs) or inhibit (Gi) adenylyl cyclase?

A

which family of G protein is linked to a GPCR in a cell type

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11
Q

Adenylyl Cyclase

A

integral membrane enzyme. Enzymatic activity can be stimulated or inhibited by several different proteins, enzymatically utilizes energy from hydrolysis of ATP->AMP + PPi to form cAMP. Generated cAMP quickly

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12
Q

cAMP

A

second messenger produced by adenylyl cyclase.

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13
Q

What is the target of cAMP

A

family of enzymes called protein kinases

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14
Q

Protein Kinase A

A

2 regulatory subunits, 2 catalytic subunits

Catalytic subunits can phosphorylate intracellular effectors.

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15
Q

How does cAMP and protein kinase A work together?

A

cAMP docks with the protein kinase A regulatory cAMP binding sites, and the protein kinase A catalytic subunits are released.

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16
Q

What do active protein kinase A catalytic subunits do?

A

phosphorylate target proteins and enzymes to elicit the function of intracellular effectors driven by extracellular signals

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17
Q

intracellular effectors

A

ion channels, enzymes, DNA binding proteins.

18
Q

Phosphorylation

A

can positively or negatively affect the activity of an intracellular effector. It does NOT always turn something on.

19
Q

protein phosphatases

A

enzymes that hydrolytically cleave phosphate esters and thus remove/dephosphorylate effector proteins that are phosphorylated by protein kinases

20
Q

Which amino acids can be phosphorylated

A

Serine, threonine, tyrosine. they contain an -OH functional group

21
Q

cAMP phosphodiesterase

A

is an enzyme that rapidly converts cAMP to 5’-AMP (NOT a signaling molecule)

22
Q

Disruption of normal adenylyl cyclase activity

A

A1 interacts with ADP-ribosylation factors, which catalyzes ADP-ribosylation of G alpha so it can never turn off

23
Q

What is the regulation pathway for intermediary metabolism?

A

inositol triphosphate and Diacylglycerol signaling

24
Q

phospholipase C

A

membrane localized, cleaves lipid bilayer PIP2-IP3 and DAG

25
IP3
inositol 1,4,5-triphosphate binds ER receptor, releasing Ca2+ from ER to cytosol
26
PIP2
Phosphatidylinositol 4,5-biphosphate is a membrane phospholipid
27
Protein Kinase C
major target activated by DAG and Ca2+, functions with Ca2+ to synergystically promote (metabolic) responses by phosphorylating proteins, it is cAMP dependent. What promotes change in cellular program
28
What ligand stimulate IP3 and DAG signaling
nurotransmitters, hormones, and growth factors
29
Ca2+ as a signaling molecule in the liver
calcium released from ER, 4 calcium bind to calmodulin, calmodulin-Ca complex results in a conformational change that permits interactions with and activation of enzymes involved in metabolism
30
coordination of energy metabolism is controlled by
Primary-two peptide hormones-insulin and glucagon | Supporting-two catecholamines-epinephrine and norepinephrine
31
insulin
a protein hormone that is water soluble produced in beta cells in the islets of Langerhans in the pancreas stored in secretory granules anabolic effector
32
what does insulin promote
production of glycogen, triacylglycerides, protein
33
regulation of insulin secretion
beta cell secretion of insulin is coordinated with alpha cell secretion of glucagon
34
the rate of glucose use by peripheral tissues as a result of insulin secretion is counter balanced by
glucagon release, hepatic glucose production rates
35
increased insulin secretion from glucose
results in coordinated increase in insulin rate, beta cells produce more insulin, glucagon levels decrease
36
increased insulin secretion from amino acids
increased amino acid concentration and insulin secretion stimulated, glucagon release is unregulated to compensate for the increased insulin and thus glucose uptake
37
increased insulin secretion from GI hormones
peptide hormones are released from the small intestine as anticipatory insulin release stimulators in response to food ingestion, insulin secretion is greater when glucose is ingested in contrast to given IV
38
factors that negatively affect insulin secretion
scarcity of dietary fuels such as glucose and amino acids | Increase in blood levels of epinephrine
39
Epinephrine release is regulated by the nervous system and is secreted by the adrenal medulla in response to
stress, trauma, extreme exercise
40
epinephrine directly affects mobilization of
glucose from the liver | fatty acids from adipose tissue
41
what can override the normal glucose-stimulated release of insulin?
epinephrine