Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

KIN 217 - Human Biochemistry > Chapter 13 > Flashcards

Chapter 13 Flashcards

1
Q

Signal transduction pathways are important for cells and organisms to be able to __________ and respond _______________

A

sense their environment; with the proper biochemical processes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Common components to the signal transduction cascades:

A
  1. Release of a primary messenger
  2. Reception of primary messenger
  3. Relay of information by the second messenger
  4. Activation of effectors that directly alter the physiological response
  5. Termination of the signal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe step 1: the release of a primary messenger

A

(1) A stimulus, such as a wound or a digested meal, triggers the release of signal molecule, called primary messenger

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is a primary mesenger?

A

The information embodied in the interaction between the ligand and its receptor molecule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Most signal molecules are too _____ and too ______ to pass through the cell membrane or through transporters. Thus, the information presented by signal molecules must be transmitted _________________ without the molecules entering the cell themselves

A

Large; polar; across the cell membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe step 2: the reception of a primary messenger

A
  • Because signal molecules are too large and too polar to pass through the cell membrane, the information presented by those signal molecules must be transmitted across the cell membrane without the molecules entering themselves
  • (2) Membrane receptors transfer information presented by primary messengers from the environment to a cell’s interior
  • (3) A binding site on the extracellular domain specifically recognizes the signal molecule, also called ligand - a small molecule that binds to a protein, inducing a specific structural change (ex. a steroid is a ligand for the steroid-hormone receptor)
  • (4) Formation of receptor-ligand complex alters the tertiary or quaternary structure of receptor and intracellular domain
  • (5) Structural changes in the receptors bound to ligands are not sufficient to yield a response from cell. The info conveyed by receptor must be transduced into other forms of info that can alter the cell’s biochemistry
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

True or False: Structural changes in the receptors bound to ligands are not sufficient to yield a response from cell

A

True: The info conveyed by receptor must be transduced into other forms of info that can alter the cell’s biochemistry

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe step 3: the relay of information by the second messenger

A

Structural changes in receptor lead to changes in concentration of small molecules called second messengers (small intracellular signal molecule whose concentration changes in response to a primary messenger) that are used to relay info from the receptor-ligand complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are some examples of second messengers?

A

Prominent second messengers include

  • cyclic AMP (cAMP, cyclic adenosine monophosphate)
  • cyclic GMP (cGMP, cyclic guanosine monophosphate)
  • calcium ion
  • inositol 1,4,5-trisphosphate (IP3)
  • diacylglycerol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Second messengers have many consequences. Two of them include:

A

(1) Second messengers are free to diffuse to other compartments, ex. nucleus, where it can influence gene expression and other processes

(2) Signal may be amplified significantly in the generation of second messengers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe step 4: activation of effectors that directly alter the physiological response

A

The effect of the signal pathway is to activate (or inhibit) the pumps, enzymes, and gene-transcription factors that directly control metabolic pathways, gene expression, and processes (ex. such as nerve transmission)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe step 5: termination of the signal

A
  • After a signaling process has been initiated and the information has been transduced to affect other cellular processes, signaling process must be terminated.
  • W/o termination, cells lose their responsiveness to new signals
  • Signaling processes that fail to be terminated properly may lead to uncontrolled cell growth and cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the three major classes membrane receptors?

A
  1. Seven-transmembrane-helix receptors associated w/ heterotrimeric G-proteins
  2. Dimeric membrane receptors that recruit protein kinases
  3. Dimeric protein receptors that are protein kinases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are seven-transmembrane-helix (7TM) receptors

A
  • They transmit info initiated by signals as photons, hormones, neurotransmitters, odorants, etc.
  • They change conformation in response to ligand binding and activate G-proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

7TM receptors mediate a multitude of biological functions by responding to a variety of different ligands or signaling molecules. List examples of these biological functions

A
  • Hormone action
  • Hormone secretion
  • Neurotransmitters
  • Chemotaxis
  • Exocytosis
  • Control of BP
  • embryogenesis
  • Cell growth and differentiation
  • Development
  • Smell
  • Taste
  • Vision
  • Viral infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Mutations in 7TM receptors and their associated components cause a host of diseases. List some examples of these mutations/diseases

A
  • Color blindness
  • Familial hypogonadism
  • Short stature due to mutated growth hormone receptor
  • Extreme obesity
  • Congenital hypothyroidism
  • Incomplete bowel innervation (Hirschsprung disease)
  • Precocious puberty
  • Night blindness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

7TM receptors contain ______ helices that span across the membrane bilayer

A

7

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

An example of a 7TM receptor that responds to chemical signals is called __________________. This protein binds ___________ (adrenaline), a hormone responsible for ___________ response

A

B-adrenergic receptor; epinephrine; fight or flight

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Ligand-receptor binding activates __________________

A

GTP-binding proteins (G-proteins)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What does GTP stand for?

A

Guanosine triphosphate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Explain the steps to epinephrine binding to it’s receptor and the activation of GTP-binding (G-proteins) in order

A
  1. Ligand (epinephrine) binds to receptor (B2-adrenergic). Ligand-receptor binding activates
    GTP-binding proteins (G-protein)
  2. G-protein exchanges exchanges GDP for GTP
  3. Dissociation of Gα & Gβy subunits
  4. Activated Gα subunit activates adenylate
    cyclase
  5. Activated adenylate cyclase generates cAMP and high
    concentrations of it with help of ATP
  6. cAMP will now act as a second messenger and activate protein kinase A (PKA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

G-proteins serve as important ____________

A

molecular switches

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

There are multiple genes for G-alpha proteins. The most common is G-alpha-S for _________. There are also G-alpha-I, for __________

A

stimulation (Gs); inhibitors (Gi)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the two main types of G-proteins?

A
  1. Large multimeric G-proteins (ex. GCPRs = G-protein coupled receptors)
  2. Small monomeric G-proteins (ex. Ras proteins)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Adenylate cyclase generates _________ which propagates signal transduction pathway

A

cAMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Explain the steps to cAMP stimulating the phosphorylation of target proteins through activation of PKA (protein kinase A)

A

(1) PKA has two pairs of subunits: catalytic (blue) and regulatory (yellow). In absence of cAMP, the R2C2 complex is catalytically inactive

(2) The binding of cAMP to the regulatory subunits releases catalytic subunits, which are enzymatically active on their own

(3) Activated PKA then phosphorylates specific serine and threonine residues in many target proteins to alter their activity. The alteration in activity is due to structural and ionic changes that result from the introduction of the large negatively charged phosphate functional group

(4) The cAMP cascade is turned off by cAMP phosphodiesterase - an enzyme that converts cAMP into AMP, which does NOT activate PKA

(5) Blue and Yellow subunits subsequently join to reform inactive enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Since protein kinase A is a kinase, the activity of this molecule is based on its ability to ________ target proteins

A

phosphorylate

28
Q

Kinases _____ phosphates

A

add

29
Q

Phosphotases _____ phosphates

A

remove

30
Q

Describe the three ways termination can take place of epinephrine-imitated pathway

A

(1) The G-alpha subunit has intrinsic GTPase activity, which will cleave the bound GTP back into GDP; the G-alpha unit that is bound to GDP will reassociate with the beta and gamma subunits. Altogether, this will terminate the activity of the G-protein and turn off the pathway

(2) The epinephrine-initiated pathway can also be shut-off through cAMP phosphodiesterase activity which converts cAMP back into AMP. AMP is unable to activate protein kinase

(3) The epinephrine-initiated pathway can also be shut-off through the dissociation of the ligand from the receptor. If the receptor no longer has the bound ligand, the receptor will no longer be able to signal to the intracellular tails of the receptor or to the inside of the cell

31
Q

True or False: IP3 directly causes the rapid release of Ca2+ from intracellular stores—the endoplasmic reticulum and, in muscle cells, the sarcoplasmic reticulum

A

True

32
Q

Phosphoinositide cascade, (like the adenylate cyclase cascade), converts ________ signals into ________ ones

A

extracellular; intracellular

33
Q

Describe phosphoinositide Cascade

A

(1) Phospholipase C activation results in cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) plus diacylglycerol (DAG)

(2) IP3 associates w/ a membrane protein called IP3 receptor or IP3 gated channel, which causes the rapid release/flow of Ca2+ from the endoplasmic reticulum into the cell cytoplasm

(3) The elevated level of Ca2+ in the cytoplasm then triggers a variety of biochemical processes such as smooth-muscle contraction, glycogen breakdown, and vesicle release

(4) DAG (the molecule formed by receptor-triggered hydrolysis of PIP2) is also a second messenger that, in conjunction with Ca2+, helps to activate protein kinase C (PKC) - a protein kinase that phosphorylates serine and threonine residues in many target proteins

34
Q

What are the class of receptors that recruit protein kinases?

A

dimeric membrane receptors

35
Q

Describe the steps to receptor dimerization

A
  1. The receptor arms will exist as monomeric integral membrane proteins w/ an extracellular and an intracellular domain on the surface of a cell
  2. These domains are joined by an intramembrane alpha helix. Upon hormone or ligand binding, receptor dimerization will occur
  3. Ligand binding shifts the quaternary structure resulting in the formation of receptor dimers
36
Q

Describe further steps of receptor dimerization and cross-phosphorylation

A
  1. Dimerization of the extracellular domains of the receptor brings together the intracellular domains as well. Associated with each intracellular domain is a molecule of a tyrosine protein kinase, termed Janus kinase 2 (JAK2), in an unactivated form
  2. Tyrosine kinases phosphorylate proteins on the hydroxyl group of tyrosine residues
  3. Dimerization of the growth-hormone receptors bring together the JAK2 proteins associated with each intracellular domain. Each of the kinases phosphorylates its partner, resulting in the activation of the kinases
                                OR
  4. With receptor dimerization upon ligand binding, intracellular domains are brought together and can recruit intracellular kinases
  5. Kinases associated with intracellular domain can cross phosphorylate the cytoplasmic tails of receptors in cross phosphorylation events (spread out, and face opposite direction)
  6. Janus kinase 2 (JAK2), a tyrosine kinase, can add phosphates on tyrosine residues of intracellular domains of receptor tails. Phosphates are added to hydroxyl group of tyrosine residue = activated JAK2
37
Q

Some growth factors and hormone receptors (ex. epidermal growth factor and insulin) bind to receptors that are tyrosine kinases, called ____________________

A

receptor tyrosine kinases (RTK)

38
Q

Describe the process of epidermal growth factor (EGF) binding to extracellular domains of transmembrane receptors that have tyrosine kinase domains within their intracellular domains

A

(1) Epidermal growth factor (EGF) binds to its receptor (EGFR)
(2) Binding leads to phosphorylation of receptor tails
(3) Phosphorylated receptor tails bind to Sos, recruited by key adapter protein, GrB-2.
(4) Sos then binds to Ras and activate it
(5) Sos stimulates the exchange of GTP for GDP in Ras
(6) Activated Ras binds to protein kinases and stimulates them

39
Q

What is Ras?

A
  • Regulates cell growth through serine or threonine protein kinases
  • A key component of the EGF pathway, as well as other signal transduction pathways
  • A member of the family of signaling proteins called small-proteins or small GTPases
40
Q

Ras is _____ when bound to GTP and ________ when bound to GDP

A

active; inactive

41
Q

True or False: Ras does not have intrinsic GTPase activity

A

False: Ras has intrinsic GTPase activity, which controls signal duration

42
Q

True or False: Additional small molecules (GAPs = GTPase activating proteins; and GEFs = guanine nucleotide exchange factors) help to modulate the GTPase activity of Ras

A

True

43
Q

True or False: Ras proteins have a greater reliance on these other small molecules (GAPS, GEFs) to shut off cascade

A

True

44
Q

The Ras superfamily of GTPases are a large superfamily of proteins group into subfamilies. Name the Subfamilies and their funtions

A
  1. Ras - Regulates cell growth through serine or threonine protein kinases
  2. Rho - Reorganizes cytoskeleton through serine or threonine protein kinases
  3. Arf - Activates the ADP-ribosyltransferase of the cholera toxin A subunit; regulates vesicular trafficking pathways; activates phospholipase D
  4. Rab - Plays a key role in secretory and endocytotic pathways
  5. Ran - Functions in the transport of RNA and protein into and out of the nucleus
45
Q

True or False: Insulin is among the principal hormones that regulate metabolism

A

True

46
Q

Insulin is a _________ released by the_______ cells of the ________ after a meal has been eaten and, is the biochemical signal designating the _________ state

A

hormone; beta; pancreas; fed

47
Q

True or False: Insulin consists of three polypeptide chains linked by disulfide bonds

A

False: Insulin consists of two polypeptide chains linked by disulfide bonds

48
Q

True or False: The polypeptide hormone insulin is secreted when blood glucose levels are low

A

False: The polypeptide hormone insulin is secreted when blood glucose levels are high

49
Q

The insulin receptor is ________________ with two _____ subunits on extracellular side (outside cell) and two ______ subunits on intracellular side (inside cell)

A

receptor tyrosine kinase (RTK); alpha; beta

50
Q

True or False: Similar to the other members of RTK family of receptors, insulin receptor will not exist as a dimer and will need the ligand-binding association to occur for dimerization to occur

A

False: Unlike other members of RTK family of receptors, insulin receptor exists as a dimer even in the absence of insulin

51
Q

True or False: The kinase activity of the insulin RTK exists on the extracellular alpha subunits

A

False: The kinase activity of the insulin RTK exists on the intracellular beta subunits

52
Q

Describe the steps to insulin binding

A

(1) Insulin binds to receptor, which results in changes to the quaternary structure of the receptor. This change in structure further results in the cross-phosphorylation and activation of the two intracellular kinase domains, activating the kinase activity of the cytoplasmic tails

(2) The activated kinase phosphorylates additional sites within the receptor. Phosphorylated sites on the receptor act as binding sites for insulin-receptor substrates, IRS-1.

(3) The IRS proteins are phosphorylated by tyrosine kinase activity of the insulin receptor.

(4) In phosphorylated form, IRS act a as adapter proteins. Lipid kinase phosphoinositide 3-kinase binds to the phosphorylated sites on IRS-1 through its regulatory domain, then converts PIP2 into PIP3

(5) Binding to PIP3 activates PIP3-dependant protein kinase (PDK1), which phosphorylates and activates kinases such as Akt (also called protein kinase B or PKB), another serine or threonine protein kinase

(6) Activated Akt can then diffuse throughout the cell to continue the signal transduction pathway

53
Q

How will termination of the insulin signal transduction pathway occur?

A
  • Signal termination will be mediated by protein phosphatases, which remove phosphates from the activated proteins in the insulin signal-transduction pathway, terminating the insulin signal
  • Lipid phosphatases contribute to signal termination by converting PIP3 into PIP2
54
Q

True or False: Ca2+ is an important second messenger in eukaryotic signal transduction pathways

A

True

55
Q

Protein ______ is a common Ca2+ sensor

A

calmodulin

56
Q

Calmodulin has _______ Ca2+ binding sites called ________, activated upon binding

A

four; EF hands

57
Q

True or False: The Ca2+ calmodulin complex activates a variety of enzymes, pumps, and biochemical targets

A

True

58
Q

True or False: The Ca2+ calmodulin complex activates the plasma membrane Ca2+ ATPase AND calmodulin-dependent protein kinase (CaM kinase)

A

True

59
Q

True or False: Ca2+ does not play a role in phosphoinositide cascade

A

False: Ca2+ does play a role in phosphoinositide cascade

60
Q

True or False: Potassium channels have four binding sites

A

True

61
Q

True or False: Ca2+ calmodulin activates target proteins by binding to them

A

True

62
Q

True or False: If the genes encoding components of the signal-transduction pathways are altered by mutation, pathological conditions, cancer may occur

A

True

63
Q

___________ function in pathways that control cell growth and replication. Mutated versions of _______ are frequently found in human cancers

A

Proto-oncogenes; Ras

64
Q

Describe the steps of the STP in order from releasing of glucagon in the blood to the promotion of glycogenolysis

A
  1. Glucagon binds to GPCR (G-protein coupled receptor), which activates GTP-binding protein (G-protein)
  2. G-proteins releases GDP for GTP
  3. Activated G-protein activates adenylate cyclase
  4. adenylate cyclase converts ATP to cAMP
  5. cAMP activates PKA
  6. phosphorylase kinases phosphorylates glycogen phosphorylase
  7. Glycogenesis is promoted
65
Q

cAMP structure has….

A
  • one NH2 group at top of hexagon
  • 3 double bonds in hexagon
  • has two NH in hexagon
66
Q

cGMP structure has…

A
  • =o structure at top of hexagon
  • has two double bonds in hexagon
  • has NH and NH2 group in hexagon

KIN 217 - Human Biochemistry (34 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions