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Biochemistry > Chapter 12: Biochemical Signaling > Flashcards

Chapter 12: Biochemical Signaling Flashcards

1
Q

In multicellular organisms, what is the largest group of plasma membrane receptors?

A

GPCRs

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2
Q

Signal transduction is the conversion of information into a _______ change

A

chemical change

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3
Q

Receptors are found on the _____ side of the membrane

A

extra-cellular

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4
Q

What is a receptor?

A

A membrane bound or soluble protein which causes a physiological effect after binding its ligand

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5
Q

Four common receptor types

A

G-protein coupled receptors (epinephrine)

Enzyme-linked receptors (insulin)

Ligand-gated ion channels (nicotinic acetylcholine)

Nuclear receptors (steroids)

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6
Q

Types of ligands for receptors

A
  • Small ions (ferric ion)
  • organic molecules (NTs like adrenaline)
  • Polysacchardies (heparin)
  • Peptides (insulin)
  • proteins (vascular endothelial growth factor)
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7
Q

Explain Signal Transduction Specificity

A

A signaling ligand fits to the binding site of its complementary ligand - molecular complementarity exists b/w the signal and receptor… only binds what its looking for and nothing else

  • results from high affinity of receptors for their ligands
  • mediated by noncovalent forces
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8
Q

What is signal transduction amplification?

A

When an enzyme activates other enzymes, the number of molecules affected increases in a cascading manner

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9
Q

What are scaffold proteins ?

A

Non-enzymatic proteins that bring together enzymes within a cascade

  • don’t do anything besides putting things where they need to be
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10
Q

What does signal transduction MODULARITY refer to?

A

modular means the receptor recognizes multiple

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11
Q

What is signal transduction?

A

The conversion of information into a chemical change

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12
Q

What happens when a receptor becomes desensitized?

A

Desensitization occurs when a signal is continuously present and the receptor system no longer responds to the signal

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13
Q

What is integration?

A

The ability of a receptor system to receive multiple signals and in turn produce a unified response

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14
Q

What does it mean for signaling pathways to be divergent?

A

Divergent means they are branched rather than linear

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15
Q

What is response localization?

A

When the components of a signaling system are confined to a specific subcellular structure (a raft in the plasma membrane, for example), a cell can regulate a process locally, without affecting distant regions of the cell.

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16
Q

Characteristics of GPCRs

A

GPCRs = Guanosine nucleotide-binding protein

  • alpha helical integral membrane proteins
  • heterotrimeric (alpha, beta, gamma)
  • G-proteins mediate signal transduction from GPCRs to other target proteins

example of GPCR: B-adrenergic receptor system

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17
Q

Gated ion channels

A

open and close in response to the binding of chemical ligands or changes in transmembrane potential. The simplest signal transducers

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18
Q

Enzyme-linked receptors

A

enzymatic activity occurs on the cytoplasmic side, triggered by ligand binding on the extracellular side

-ex: tyroisne kinase which catalyze the phosphorylation of Tyr residues

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19
Q

Agonist vs Antagonist

A

Agonist - binds receptor to mimic response of ligand , are molecules (natural ligands or their structural analogs) that bind a receptor and produce the effects of the natural ligand

Antagonist- binds receptor but causes no response, thereby blocking the effects of agonists

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20
Q

Components of the GPCR

A
  • a plasma membrane receptor with seven transmembrane helical segments
  • a G protein that cycles between active (guanosine triphosphate (GTP)-bound) and inactive (guanosine diphosphate (GDP)-bound) forms
    -an effector enzyme (or ion channel) in the plasma membrane that is regulated by the activated G protein
    -An extracellular signal such as a hormone, growth factor, or neurotransmitter is the “first messenger” that activates a receptor from outside the cell
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21
Q

When are GPCRs active?

A

when GTP bound

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22
Q

When are GPCRs inactive?

A

when GDP bound and therefore in the trimeric form

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23
Q

What subunit contains the binding site for GDP/GTP on the GPCR?

A

the alphs subunit

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24
Q

What is the first messenger in GPCR

A

First messenger = some extracellular signal that activates a receptor from outside. the cell

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25
Q

What is a second messenger in GPCR pathway?

A

second messengers are usually CAMP, diacylglycerol, IP3, or Ca2+ which either inhibit or activate one or more downstream targets, usually protein kinases

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26
Q

GPCRs effect signal transduction through interaction with _____?

A

through interaction with heterotrimeric G proteins (signaling proteins with alpha, beta, gamma subunits)

27
Q

What type of receptors are Beta-adrenergic receptors?

A

GPCRs

28
Q

The Beta-adrenergic system acts through which type of messenger?

A

The second messenger, CAMP

29
Q

Stimulation of adenylyl cyclase by Gs alpha is self-limiting, what does this mean?

A

Gs alpha has intrinsic GTPase activity that switches Gs alpha to its inactive form by converting its bound GTP for GDP

30
Q

How does the Beta-adrenergic response terminate? (3 ways)

A
  1. Desensitization - occurs when the concentration of the ligand (epinephrine) in the blood drops below the Kd for its receptor
  2. By hydrolysis of GTP to GDP catalyzed by the intrinsic GTPase activity of the G-protein
  3. By removal of the second messenger, cAMP
31
Q

How do receptor tyrosine kinases activate kinase domains?

A

with autophosphorylation

32
Q

Growth factor associated with colon cancer

A

Epidermal growth factor

33
Q

What are oncogenes

A

mutated versions of genes encoding signaling proteins involved in cell cycle regulation

they lead to tumor formations

34
Q

What are growth factors?

A

Extracellular signals that activate nuclear transcription factors

35
Q

What family of kinases controls the timing of the cell cycle ?

A

Cyclin dependent kinases (CDKs)

36
Q

What is the regulatory subunit of kinases

A

CYCLIN

37
Q

CDKs are only active when

A

when bound to cyclin

38
Q

What occurs when the regulatory mechanisms that limit cell division are defective and cells undergo unregulated division

A

cancer

39
Q

The inside of a cell is more (positive or negative) compared to the outside

A

The inside is more negatively charged
– this allows positively charged species to be able to flow in the cell

40
Q

Membrane receptors consist of what two things

A

an extracellular ligand binding domain
an intracellular catalytic domain

41
Q

What second messenger is adenylyl cyclase responsible for catalyzing?

A

cAMP, synthesized as a result of epinephrine binding to GPCR

42
Q

What does CAMP activate

A

Protein Kinase A (PKA)

43
Q

What is the result of PKA activation

A

PKA activation leads to the activation of enzymes that release glucose from glycogen

44
Q

What two molecules mediate desensitization in epinephrine

A

BARK (Beta adrenergic receptor kinase) and Beta ARRESTIN

45
Q

This type of messenger is a low MW metabolite or an inorganic ion that changes in concentration due to the effector enzyme or ion channels. They function to activate or inhibit downstream targets

A

A second messenger

46
Q

What molecule cleaves PIP2 to form IP3 and diacylglycerol?

A

PLC (phospholipase C)

47
Q

Once active, what does IP3 bind to?

A

receptor-gated Ca2+ channel, releasing Ca2+

48
Q

What two molecules are responsible for activating Protein Kinase C

A

diacylglycerol and the calcium that was released by IP3

49
Q

What does PKC do after being activated?

A

PKC phosphorylates cellular proteins that go on to produce cellular responses to the hormone

50
Q

How is IP3 created?

A

Through PLC cleavage of PIP2

51
Q

What molecule activates PI3K and how

A

PI3K is activated by phosphorylated IRS1 which activates PI3K by binding to its SH2 domain

52
Q

How is GSK3 inactivated?

A

GSK3 becomes inactive once phosphorylated by PKB…so if PKB is activated then GSK3 will become inactivated

53
Q

Result of GSK3 inactivation?

A

Once inactive, GSK3 cannot convert glycogen synthase into its INACTIVE form (which occurs via phosphorylation) and thus GS remains active

54
Q

What is occurring when GS is active?

A

When GS is active (not phosphorylated) then the synthesis of glycogen from glucose is occurring

55
Q

What do SH2 domains do

A

SH2 domains bind phosphotyrosine (pTyr) residues in binding partners

56
Q

How are hormones able to diffuse across the plasma membrane?

A

Due to their hydrophobicity

57
Q

Where are hormone receptors located?

A

their receptor proteins are located in the nucleus

58
Q

What are the specific regulatory sequences in DNA that interact with receptor proteins after hormone binding?

A

Hormone response elements (HRE)

59
Q

What is characteristic of the GRK family (G-Protein Receptor Kinase) such as the Beta-adrenergic receptor kinase?

A

GRKs phosphorylate GPCRs on their carboxyl-terminal cytoplasmic domains and play roles similar to that of βARK in the desensitization and resensitization of their receptors

60
Q

How is it that so many types of signals can be mediated by a single-second messenger such as cAMP?

A

Due to the confinement of a signaling process to a specific region of the cell by adaptor proteins

61
Q

Insulin regulates what two things

A

metabolic enzymes and gene expression

62
Q

What is the physical makeup of the INSR (insulin receptor protein)

A

two identical α subunits protruding from the outer face of the plasma membrane and two transmembrane β subunits with their carboxyl termini protruding into the cytosol — a dimer of αβ monomers

63
Q

What transfer occurs in order for PI3K to convert PIP2 to PIP3

A

The transfer of a phosphoryl group from ATP

Biochemistry (10 decks)

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