Learning Objectives Flashcards

1
Q

properties of malignant cancer cells

A
  • unresponsive to normal signs of proliferation control
  • de-differentiated
  • invasive
  • metastatic
  • clonal origin (came from one cell)
  • lack contact inhibition
  • more glucose transport
  • immortal
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2
Q

steps for carcinogenesis

A
  • normal cell
  • increased proliferation
  • neoplasia
  • carcinoma
  • metastasis
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3
Q

cytogenetic abnormalities associated with malignancy

A
  • chromosome translocation, deletion
  • bringing a promoter near an oncogene
  • interrupting transcription
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4
Q

retinoblastoma gene is on chromosome _____

A

13q14

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5
Q

retinoblastoma gene loss can be detected by ________________

A

PCR, Southern blot

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6
Q

RB is a ___________ gene

A

tumor-suppressor

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7
Q

APC encodes for a protein that regulates localization of ___________ protein

A

beta-catenin

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8
Q

When APC is lost, beta-catenin ________________

A

goes to nucleus to produce transcription of oncogenes

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9
Q

p53 is (homozygous/heterozygous) but a ___________________

A

heterozygous, tumor suppressor

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10
Q

adenovirus E18, HPV E6, etc. have __________ that inactivate _____

A

oncogenes, p53

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11
Q

v-src

A

phosphorylates tyrosine residues in other proteins

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12
Q

v-erb

A

mimics epidermal growth factor receptor

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13
Q

v-sis

A

mimics platelet-derived growth factor

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14
Q

Li-Fraumeni criteria

A
  • proband with sarcoma diagnosed before age 45
  • first degree relative with any cancer before age 45
  • first or second degree relative with any cancer before age 45 or a sarcoma at any age
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15
Q

clinical manifestations of Von Hippel-Lindau (VHL) disease

A
  • hemangioblastoma (CNS, retina)
  • clear cell renal cell carcinoma
  • bilateral kidney cysts
  • pheochromocytoma
  • pancreatic cysts and pancreatic neuroendocrine tumors
  • endolymphatic sac tumor
  • cystadenomas of genitourinary tract

(BE HPPCC)

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16
Q

VHL is a _________ gene located on chromosome ___

A

tumor-suppressor, 3p25-26

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17
Q

VHL targets ______ for ubiquination and degradation

A

HIF

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18
Q

phospholipid

A

glycerol-3-phosphate backbone with two fatty acyl chains (saturated or mono- or poly-unsaturated) at one end and polar head group at other

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19
Q

sphingolipid

A
  • long acyl unit (sphingosine) with either of two polar head groups and an attached fatty acid chain
  • NH instead of one of the C’s
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20
Q

cholesterol

A

hydroxylated ring at one end and fatty acid chain on other

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21
Q

Uptake and synthesis of cholesterol are regulated by ________

A

SREBP

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22
Q

With low cholesterol, the transcription factor is released from SREBP via ______________________

A

RIP (regulated intramembrane proteolysis)

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23
Q

Proteases that cleave SREBP release ___________

A

basic helix-loop-helix

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24
Q

_______ binds SREBP and sterols like cholesterol

A

SCAP

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25
Q

_______ binds SCAP when cholesterol is high

A

Insig

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26
Q

plasma volume

A

3 liters

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27
Q

ECF volume

A

13 liters + 5 for “third space”

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28
Q

ICF volume

A

27 liters

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29
Q

physical forces that can determine the gating properties of ion channels

A
  • electric field (voltage-gated, membrane potential)
  • mechanical (stretch)
  • chemical (synaptic receptors)
  • temperature
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30
Q

mechanisms cells evolved to keep from swelling and bursting

A
  • make cell membrane impermeable to water
  • build wall around cell which resists osmotic pressure
  • balance water concentrations osmotically
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31
Q

molarity

A

number of moles of solute/L of solution

-measure of concentration

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32
Q

osmolarity

A

total concentration of solute molecules (sum of molarity)

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33
Q

equivalents

A

number of “combining weights” of an ion per liter

-convert mosM for each ion, multiply most by valence of each ion

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34
Q

tonicity

A

effect of a solution on a cell

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35
Q

_____ protein regulates dissociation of SNARE protein

A

NSF

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36
Q

arterial blood pH

A

7.34-7.44

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37
Q

venous blood pH

A

7.28-7.42

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38
Q

concentration of HCO3- in blood

A

24mmHg

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39
Q

PCO2 in blood

A

40mmHg

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40
Q

One clinical exam finding that suggests irritable bowel disease is _________

A

erythema nodosum

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41
Q

major metabolic disturbances in DKA

A
  • hyperglycemia (elevated blood sugar)
  • acidosis
  • potassium derangement
  • dehydration
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42
Q

action of insulin in liver

A
  • stores glucose (as glycogen) and lipid

- stops lipid and glycogen breakdown

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43
Q

action of insulin in muscle

A
  • stores glucose

- makes protein

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44
Q

action of insulin in adipose

A

-stores glucose and triglyceride

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45
Q

loss of RB gene can occur via…

A
  • local events
  • somatic recombination
  • chromosome loss
  • loss and duplication
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46
Q

In FAP, the mutation is a change from ________ to __________

A

glutamic acid to glutamine

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47
Q

BRCA1 is important in regulating _____________

A

quality control for DNA damage

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48
Q

Most mutations in p53 are _________ mutations

A

missense

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49
Q

Li-Fraumini syndrome is inherited in an ________ fashion

A

autosomal dominant

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50
Q

common ways cancer-associated “hits” can occur

A
  • point mutation (activating oncogene or suppressing tumor inactivation)
  • amplification
  • deletion
  • epigenetic silencing via methylation
  • insertion of retrovirus containing an oncogene
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51
Q

T/F: In Li-Fraumini syndrome, “hits” can be on different genes

A

true

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52
Q

VHL comes from a ________ mutation in ______ of the VHL gene

A

missense, exon 3

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53
Q

VHL is an ___________ inherited cancer syndrome

A

autosomal dominant

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54
Q

VHL is a ___________ gene

A

tumor-suppressor

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55
Q

Where are CNS hemangioblastomas found in patients with VHL?

A

cerebellum, brainstem base, cervical spine (not forebrain)

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56
Q

actions of VHL protein

A
  • regulates HIF (hypoxia inducible transcription factor)
  • suppresses aneuploidy
  • microtubule stabilization/primary cilia maintenance
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57
Q

Gag encodes for ________

A

internal virion proteins

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58
Q

Env encodes for ______________

A

membrane glycoproteins

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59
Q

Pol encodes for ______________

A

reverse polymerase

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60
Q

V-myc mimics ________________

A

c-myc proto-oncogene (cell growth/division)

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61
Q

_____________ are the most common cause of death in patients with Von Hippel Lindeau

A

renal cell carcinomas

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62
Q

Describe the position of activation and inactivation gates in action potentials

A
  • rest: activation closed, inactivation open
  • rising: both open
  • falling: activation open, inactivation closed
  • hyperpolarization: both closed
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63
Q

causes of hyperkalemia (2)

A
  • K+ escaping from cells

- kidney that can’t keep [K+]o below 5mM

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64
Q

systemic therapies for metastatic renal cell carcinoma include…

A
  • vascular endothelial growth factor receptor (VEGF-R) tyrosine kinase inhibitors
  • MTOR inhibitors
  • immunotherapies
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65
Q

Gating of ion channels is controlled by… (3)

A
  • temperature (hot/cold)
  • mechanical deformation
  • membrane potential
  • extracellular chemicals (taste, olfaction, neurotransmitters)
  • intracellular second messengers (ATM, cAMP, Ca2+)
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66
Q

major functions of the ER

A
  • synthesis of lipids
  • control of cholesterol homeostasis
  • synthesis of proteins on membrane bound ribosomes
  • co-translational folding of proteins and early post-translational modifications
  • quality control
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67
Q

major functions of golgi

A
  • synthesis of sphingolipids
  • post-translational modification
  • proteolytic processing
  • sorting proteins and lipids for post-golgi compartments
68
Q

pentameric ligand gated channels

A
  • cys-loop family

- each subunit has four transmembrane alpha helices

69
Q

ionotropic glutamate receptors (NDMA)

A

two of the four subunits bind glutamate and other two bind glycine

70
Q

chloride channels

A
  • gates open and close independently of each other
  • H+-Cl- exchangers
  • CLC chloride channels stabilize resting membrane potential
71
Q

factors that affect channel selectivity

A
  • charge (ionic valence too)
  • size
  • dehydration
  • number of binding sites
  • gating of Kv and Nav channels
72
Q

p53 is a ______________________

A

transcription factor

73
Q

p53 regulates ___________ and _________________

A

microRNA, protein-coding genes

74
Q

reflection coefficient

A

how well the membrane reflects the substance (0 = water, 1 = impermeable)

75
Q

equilibrium potential of RBC

A

-5

76
Q

equilibrium potential of WBC

A

-30

77
Q

equilibrium potential of neuron

A

-70

78
Q

equilibrium potential of muscle

A

-80

79
Q

equilibrium potential of glial cells

A

-90

80
Q

barrier nucleoporins contain ____________ repeats

A

phenylalanine-glycine

81
Q

What are karyopherins?

A

importins/exportins (interact directly or indirectly with cargo and FG nups)

82
Q

Ran.GTP

A
  • high levels in nucleus, helps transport cargo out of nucleus
  • gets hydrolyzed (GTP –> GDP) in cytoplasm to release cargo
83
Q

NFT2

A
  • brings cargo and Ran.GDP from cytoplasm to nucleus

- GDP –> GTP

84
Q

Brownian Ratchet

A

ATP-dependent helicase that unravels nascent RNA to allow binding, dragging nascent mRNA through nuclear pore complex (RNA movement is slower than regular protein)

85
Q

methods of regulating cargo binding to importing/exportins

A
  • intramolecular masking
  • intermolecular masking
  • affinity enhancement
86
Q

N-linked glycosylation amino acid series

A

Asn-X-Ser/Thr (X = any AA except proline)

87
Q

post-translational modifications that occur in the golgi

A
  • glycosylation (sugar and sulfates being put on)

- sorting

88
Q

______ is a sequence of amino acids that targets that amino acid to be recycled back to the ER

A

KDEL

89
Q

The cholera toxin is produced by a ________________

A

bacteriophage

90
Q

The cholera toxin binds to a ___________ via _____

A

ganglioside GM1, cAMP

91
Q

Dukoral cholera vaccine

A

killed 01 x2 and CtxB strains

92
Q

Shanchol cholera vaccine

A

killed 01 and 0139 strains

93
Q

3 major virulence factors of cholera

A
  • cholera toxin (CT)
  • o-specific polysaccharides (OPS)
  • pili: support colonization (TCP)
94
Q

ERp57 provides ER quality control by…

A

allowing formation of disulfide bonds for proper folding of enzymes

95
Q

_____________ are folding sensors in the ER

A

UDP-glucose: glycoprotein glucosyltransferases (UGGT)

96
Q

Proteasomes only degrade…

A

poly-ubiquinated proteins

97
Q

Lysosomes degrade ____________ targeted via the ____________

A

all cellular components, endocytic pathway

98
Q

Functions of macroautophagy

A
  • survival and stress conditions
  • recycle mitochondria
  • antigen presentation
  • neuroprotection
  • removes intracellular pathogens
  • aging
  • tumor suppression (if you don’t have it) and promotion (if you already have it)
99
Q

____ has only an activation gate whereas ____ has both activation and inactivation gates

A

Kv, Nav

100
Q

At the beginning of the relative refractory period, most K+ gates are…

A

open

101
Q

Myelin ________ capacitance and _________ resistance

A

decreases, increases

102
Q

What is the strongest force in nature?

A

strong nuclear force

103
Q

Each 10-fold increase in concentration gradient is equivalent to a force of ____mV

A

60mV

104
Q

Ways to diagnose hyperkalemia (2)

A
  • EKG

- K+ levels

105
Q

If an ion is at equal concentrations across a membrane, what is its equilibrium potential?

A

0

106
Q

Functions of BRCA1 and BRCA2

A
  • regulation of S-phase checkpoint
  • regulation of G2/M phase checkpoint
  • homologous recombination
107
Q

Herceptin is…

A

a synthetic antibody that attacks HER2/ERBB2 receptors

108
Q

Order smallest to largest surface area: cytoskeleton, internal membrane, plasma membrane

A

plasma membrane, internal membrane, cytoskeleton

109
Q

The apical membrane is (positive/negative) compared to basolateral

A

negative

110
Q

The major cellular defect in cholera is overproduction of ______

A

cAMP

111
Q

SRPs have an abundance of ___________ at their signal sequence binding pockets

A

methionine

112
Q

Cholera is caused by _________ diarrhea

A

secretory

113
Q

The __-subunit of proteasome cleaves after __________

A

beta, acidic amino acids

114
Q

T/F: Caveolae form without coat proteins

A

true

115
Q

Caveolin-3 is expressed in _________ and ___________ muscle

A

skeletal, cardiac

116
Q

______ competes with caspase-8 for binding to FADD and prevents apoptosis

A

FLIP

117
Q

Most cases of Li Fraumini are (inherited/sporadic). Most cases of Von Hippel-Lindau are (inherited/sporadic).

A

inherited(?), inherited (80%)

118
Q

Lipid bilayer components are synthesized in the _____

A

ER

119
Q

Features of Nav and Kv that lead to sidedness

A
  • selectivity filter near extracellular side
  • vestibule near intracellular side
  • activation/inactivation gates near intracellular side
120
Q

Direction of conductance (is/is not) unidirectional. Direction an action potential travels (is/is not) unidirectional

A

is not, is

121
Q

In chaperone-mediated autophagy, proteins are ultimately delivered to the ______________

A

lysosome

122
Q

Autophagy production protects against __________ toxicity

A

polyglutamine

123
Q

When caspases are activated, _______ gets cleaved via Bcl-2 and Bcl-xl binding to BH3 domains so autophagy can’t occur

A

beclin protein

124
Q

Nucleoporin misregulation is associated with…

A
  • cancer
  • aging
  • oxidative damage
125
Q

3 mechanisms of protein transport

A
  • vesicular
  • gated
  • transmembrane
126
Q

In DKA, you have a net K+ ______________

A

depletion

127
Q

driving force

A

at any instant, the difference between Vm and Eion

128
Q

heat map

A

gene copy number is correlated with tumor grade

129
Q

proteasomes are located in the ________ and _______

A

cytosol, nucleus

130
Q

In _____ channels, each domain is a polypeptide

A

Kv

131
Q

In Nav channels, ___ polypeptide(s) comprise(s) entire channel

A

one

132
Q

ionotropic

A

neurotransmitter is directly coupled to channel

133
Q

metabotropic

A

2nd messenger pathway that affects physically separated ion channels

134
Q

________ protein regulates G-actin concentration and ADP to ATP exchange

A

profilin

135
Q

________ is an actin-capping protein

A

gelsolin

136
Q

_______ is important for depolymerizing/severing

A

ADF/cofilin

137
Q

mechanisms for signal termination

A
  • uptake, breakdown, diffusion
  • desensitization of receptor
  • termination initiated by another signal
  • termination-dedicated enzymes
  • feedback inhibition
138
Q

During the refractory period of an AP, the activation gates are ________ and inactivation gates are ___________

A

open, shut

139
Q

Under hypoxic conditions, accumulation of HIF activates VEGF transcription, which leads to ________________

A
  • angiogenesis (blood vessel formation)
  • metabolism
  • apoptosis
  • cancer growth and survival
140
Q

Protein kinases can be classified based on… (4)

A
  • residues they phosphorylate
  • activating stimulus
  • substrate protein
  • phylogenic relationships
141
Q

______ causes nsec1 to release syntaxin (leading to zippering)

A

calcium

142
Q

metabolic acidosis vs. alkalosis

A

acidosis: too low bicarb
alkalosis: too high bicarb

143
Q

respiratory acidosis vs. alkalosis

A

acidosis: too high Pco2
alkalosis: too low Pco2

144
Q

S5 and S6 helices of ion channels form…

A

the ion conducting pathway and selectivity filter

145
Q

The strongest association allele for MS is _______

A

HLA-DRB1

146
Q

The contribution of genes on MS is likely driven by ______________ and _____________

A

gene-gene interactions, HLA effect on immune responses

147
Q

pentamer ligand-gated channels

A
  • heteropentamers
  • 4 transmembrane alpha helicies per subunit
  • M2’s surround central ion-conducting pathway
  • selective for Cl- or cations
148
Q

tetrameric ligand-gated channels

A
  • 4 subunits with 3 alpha helices per subunit
  • NDMA: 2 glutamate, 2 glycine
  • ionotropic glutamate receptors
149
Q

CLC chloride channels

A
  • dimers

- some are H+/Cl- exchangers

150
Q

aquaporins

A
  • tetramer
  • water pore and gated, central ion pore
  • excludes all ions (including H+)
151
Q

__________ cleaves the proteins in the proteasomes

A

Beta subunit
B1 = acidic aa
B2 = basic aa
B5 = chymotrypsin-like

152
Q

______ genes are required for formation of an autophagosome

A

Atg

153
Q

The ____ subunit of a microtubule is the + end and the ___ subunit of a microtubule is the - end

A

beta, alpha

154
Q

A _________ stabilizes the ends of microtubules

A

GTP cap

155
Q

Functions of microtubules

A
  • cellular cytoskeleton
  • cilia
  • cell division
  • intracellular transport
156
Q

Intermediate filaments are composed of _____________ that can form __________

A

8 tetramers, coiled coils

157
Q

Predominant proteins found in…

  • microtubules
  • intermediate filaments
  • microfilaments
A
  • microtubules: tubulin
  • intermediate filaments: vimentin, keratin, neurofilament protein, etc.
  • microfilaments: actin
158
Q

GTP favors _________ growth while ATP favors __________ growth

A

microtubule, microfilament

159
Q

Steps of actin filament formation (2)

A
  • nucleation

- extension (from + end)/retraction

160
Q

Actin filament structure is regulated by… (4)

A
  • G-actin polymerization (profilin)
  • ADP to ATP transition (profilin)
  • capping (gelsolin)
  • depolymerization/severing (ADF/cofilin)
161
Q

Functions of actin (4)

A
  • epithelial cell polarity
  • contraction
  • cell motility
  • cell division
162
Q

Two classes of signaling molecules and examples of each

A
  • lipophilic (hydrophobic): steroids

- hydrophilic (lipophobic): peptides, proteins, amino acids

163
Q

_____ is a signal terminator that breaks down cGMP to GMP

A

PDE5

164
Q

Cooperation enables regulation of enzyme activity over a (wider/narrower) range of substrate concentrations

A

narrower

165
Q

Pertussis locks the G-protein in the __________ state

A

inactive

166
Q

Cholera locks the G-protein in the _________ state

A

active