Receptors Flashcards

1
Q

What is the structure of GPCR

A

7 transmembrane helices (integral membrane protein)

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2
Q

GPCR extracellular side

A

Ligand binding

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3
Q

GPCR intracellular side

A

G protein binding —> induces conformational chance

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4
Q

Ligand binding signal active

A

GDP attached to alpha subunit unit; Ligand binds making 1 helice move inducing conformational change releasing GDP and binding GTP.

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5
Q

Ligand binding signal inactive

A

G alpha connected to GTP dissociated from Gby subunits; then G alpha hydrolyzes GTP to GDP + pi to turn inactive

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6
Q

What GPCR is Epi an agonist for

A

Beta 2 adrenergic receptor

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7
Q

What does G alpha attached to GTP have high affinity for?

A

Adenyly Cyclase which will signal to make CAMP to produce fight or flight response

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8
Q

1st messenger

A

Ligand (ex epi)

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9
Q

2nd messenger

A

Relay signal from membrane to target protein inside cell (ex CAMP targeting PKA)

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10
Q

Protein Kinase A

A

2 regulatory subunits, each with 2 camp binding sites (and alanine)

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11
Q

What happens after camp binds to the regulatory sub unit

A

The catalytic subunit will transfer a phosphate from ATP to a serine or threonine side chain on target proteins

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12
Q

What is the conformational change of PKA caused by camp?

A

2 camps disconnect catalytic subunits from regulatory subunits that then move on to Phosphorylated

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13
Q

Amplification

A

Each active enzyme can activate multiple downstream components ; nonlinear pathways; multiple steps allow levels of regulation (glucagon released for low blood glucose)

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14
Q

How is the GPCR pathway turned of

A

Reversing or blocking events that were turned on; GTP to GDP and Pi to stop AC from making camp

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15
Q

Phosphotases

A

Remove phosphate groups through hydrolysis; reverse proteins that added phosphate groups to target proteins (kinases)

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16
Q

Phosphodiesterase

A

Hydorlyze camp so pka regulatory subunits reassociate with catalytic subunits to turn pka off

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17
Q

Arrestin

A

Binds to GPCR to terminate G protein signaling by binding to GPCR

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18
Q

Stimulatory G protein

A

AC is continually active leading to increased cellular camp concentrations

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19
Q

Inhibitory G protein

A

AC is continually inhibited leasing to decrease in cellular camp concentrations

20
Q

Kinases

A

Transfer a phosphate group between nucleotides and target proteins

21
Q

Kinases

A

Transfer a phosphate group between nucleotides and target proteins

22
Q

RTK ligand binding signal activation

A

Binding to extracellular domain of RTK dimer caused conformational change in cyctolic domains where one monomer mover close to the other to Phosphorylated Try resides

23
Q

RTK activation induces what

A

A kinase cascade to amplify the signal

24
Q

Role of Tyr in RTK

A

Tyr has hydroxyl group that acts as a nucleophile for phosphorylation

25
Q

Adapter proteins

A

Require phosphate group to be active; contain phosphotyrosine binding domains

26
Q

RAS

A

Monomeric G protein (homologous to g alpha) that is activated by an adapter protein that recognizes phosphoTyr on the RTK with growth factor ligand bound to it

27
Q

How does RAS activate

A

Exchanges GDP for GTP ; initiates kinase cascade that regulates genes and cell division

28
Q

RAS steps

A

Autophosphorylation occurs, adapter proteins are recruited, RAS exchanges GDP for GTP to activate kinase cascade

29
Q

Lipid hormones relationship with receptors

A

Lipid hormones move into the cell to activate intracellular receptors causing a conformational change (dimerization) so dimer can act as a transcription factor

30
Q

Retinoate

A

Vitamin A derivative; once protonated can move across membrane

31
Q

Thyroxine (t3) and thriodothronine (t4)

A

Regulate metabolism

32
Q

Cortisol

A

Only hormone able to cross membranes directly; receptor found in the cell (cholesterol —> cortisol)

33
Q

Hormone

A

Long signaling molecule released by one tissue to target a distant tissue

34
Q

Local mediator

A

Released by one tissue to affect neighboring cells with the same tissue (short lived)

35
Q

Arachidonate

A

20 carbon FA, cleaved from membrane phospholipids by phospholipases (can be blocked by cortisol-like steroids)

36
Q

Cycloxygenase enzymes

A

Cox enzymes convert arachidonat to prostaglandin that promote pain and inflammation response

37
Q

Cox 1

A

Protect stomach lining, support kidney function, maintain clotting

38
Q

Cox 2

A

Pain, inflammation, kidney function

39
Q

Cox 2

A

Pain, inflammation, kidney function

40
Q

What do aspirin and advil inhibit

A

Both Cox 1(bad) and Cox2 (good)

41
Q

Celebrex

A

Inhibits only cox 2 but not cox1 due to steric clash

42
Q

GDP-alpha

A

Inactive ; high rector and Gby affinity

43
Q

GTP- alpha

A

Active ; low rector and Gby affinity

44
Q

G proteins

A

Hetrotimeric intracellular proteins with a, b, y subunits

45
Q

G alpha

A

Guanine nucleotide binding site

46
Q

Role of PKA

A

Phosphorylated fuel metabolism proteins