Quiz 1 Flashcards
(255 cards)
1
Q
What gene when mutated causes cystic fibrosis
A
CFTR gene
2
Q
What does the CFTR gene code for
A
chlorine transporter
3
Q
Within the cell, what does the chlorine transporter do
A
transports Cl- from inside the cell to the outside
4
Q
What does the ENaC gene code for
A
a sodium channel
5
Q
What does the sodium channel do
A
allow the transport for Na from outside to the inside
6
Q
What happens if the ENaC gene is mutated but the CFTR is working
A
There is excess hydration of the lung tissue
7
Q
What happens when the CFTR gene is mutated but the ENaC gene is not
A
there is a large influx of sodium resulting in volume depletion
8
Q
What is passive transport
A
transport that does not use ATP energy
9
Q
What types of passive transport are there
A
facillitated diffusion
simple diffusion
ionophore mediated
ion channel
10
Q
What is facilitated diffusion
A
a substrate moves down its electrochemical gradient via a channel
11
Q
What is simple diffusion
A
nonpolor compounds are drawn down their concentration gradient across the membrane
12
Q
Does simple diffusion use a channel
A
no
13
Q
What is ionophore mediated
A
ion is transported down its electrochemical gradient by binding to a protein that transports it across
14
Q
What is ion channel
A
ions move down electrochemical gradient through the channel
15
Q
What can occur to the channel in regards to struture
A
can be ligand gated or ion gated
16
Q
Before equilibrium what is the net flux of ions
A
large flux from high to low gradients, low flux from low to high gradients
17
Q
At equilibrium, what is the net flux of ions
A
no net flux
18
Q
Before equilibrium is reached, what is the Vm for ions
A
greater than zero
19
Q
Why is the Vm greater than zero
A
large flow of negative ions toward positive and large flow of positive to negative, small flow of positive to positive and negative to negative
20
Q
At equilibrium what is Vm
A
zero
21
Q
How does a channel/ transporter effect activation energy
A
lowers the delta G for transport
22
Q
How does the activation, free energy differ between simple diffusion to diffusion with a transporter
A
simple diffusion has a greater free energy whereas the diffusion with a transporter has a lower energy
23
Q
Why is simple diffusion a higher free energy
A
amount of energy to strip hydration of molecule, energy to move through hydrophobic membrane and then the energy need to rehydrate
24
Q
Why is diffusion with a transporter lower in free energy
A
easier to strip molecule, easily moves through the channel that matches its charges and easy rehydration
25
What type of protein is the glucose transporter
integral protein
26
How mmany hydrophobic sections does the glucose transporter have
12
27
What do the 12 hydrophobic sections code for
12 transmembrane segments
28
How many conformations does the glucose transporter have
2
29
What are the two confomations for the glucose transporter
T1
| T2
30
In the transmembrane alpha helices, where do the charged and polar amino acids reside
in the interior of the alpha helice
31
Where do the hydrophobic amino acids reside in the transmembrane helices
on the exterior
32
What is the T1 conformation
the channel when it is open to the exterior and allows glucose to bind to the channel
33
What is the T2 conformation
when the channel opens to the inside once glucose binds and allows its release
34
WHat does transportation have
enzyme-like properties
35
What is Kt equivalent to
Km
36
What is Kt
1/2 max velocity of glucose entry
37
In the burk. plot, what is the crossing of the y axis stand for
1/vmax
38
On the burk plot, what does the interception on x axis code for
-1/Kt
39
What is the y axis on the burk plot
1/V0
40
What is the x axis on the burk plot
1/ [S]out
41
what is an epimer
differs at 1 carbon on carbons
42
How do D and L glucose differ
on the 6th carbon one is up or down
43
How does the change on the 6th carbon affect GLUT1
changes the rate.
44
What does the chloride bicarbonate exchanger allow for
antiport exchange of Cl- for HCO3-
45
In respiring tissues what direction does Cl- and HCO3- flow
Cl- transported in
| HCO3- transported out
46
In lungs, which direction does Cl- flow and HCO3- flow
Cl- flows out
| HCO3- flows in
47
In respiring tissues what direction does CO2 flow
CO2 uptake
48
In lungs what direction does CO2 flow
CO2 released
49
What direction does the bicarbonate formula flow in respiring tissues
CO2+ H2O --> HCO3- +H (allows Cl- in)
50
WHat direction does the bicarbonate formula flow in lungs
HCO3-+ H--> H2O+ CO2
51
What enzyme allows the bicarbonate reaction to move forward or backward
carbonic anhydrase
52
What does active transport require
energy
53
Why does active transport require energy
moving substrates against gradient
54
What types of active transport are there
primary and secondary
55
What is primary transport
movement of one substrate against its electrochemical gradient
56
What is secondary transport
moves two items against substrates electrochemical gradient, driven by ion moving down its gradient
57
What is uniport transport
moving 1 substrate
58
What is cotransport
moving two substrates
59
What is symport
when two substrates move through 1 channel in same direction
60
What is antiport
when two substrates move through 1 channel in opposite directions
61
What are energetic costs
change in substrate to the product
62
How is the energetic costs calculated
deltaG= (8.315J/K*mol)(298K) ln (P/S)= J/mol
63
What is the function of ATPases
to create a gradient
64
WHat is the mechanism of the Na+K+ATPase
pump out 3 Na+ and pump 2 K+ in
| creates a -50 to -70mV gradient
65
How much of resting energy is used for the Na+K+ATPase pump
25%
66
What type of protein is the ATPase
integral protein
67
What components make up the P-type ATPase
T,S membrane domains
| A, P, N domains
68
What is the first step of P-type ATPase
calcium and ATP bind allowing N domain to move
69
After calcium and ATP bind and N domain moves what occurs
ADP phosphorylates an ASP in P domain
70
After ASP is phosphorylated what occurs
conformational change occurs causing calcium to be released to the lumen
71
What occurs after calcium is released
The A domain moves causing ADP to be released
72
After ADP is released what occurs
P domains becomes dephosphorylated
73
What happens after the P domain becomes dephosphorylated
the A domain resets
74
What happens after the A domain resets
P,T, and S domains reset to E1 conformation
75
What are two inhibitors of Na+K+ATPase
oubain
| palytoxin
76
How does ouabain inhibit
locs ATPase open and prevents a conformational change
77
How does palytoxin inhibit
locks ATPase into an open channel
78
What are aquaporins
channels that permit water to cross membrane
79
What type of flow does aquaporins have
a constant flow
80
How many genes for aquaporins have in plants
38 genes
81
Why must H3O+ be kept out of aquaporins
H+ would destroy electrochemical potentials
82
What is an ionophore for K+
valinomyocin
83
Molecules within the aquaporin that help water flow through are what
Asn
His
Arg
84
What types of signals do cells receive constant input from
pH, osmotic strength, availability of food, oxygen, light, presence of noxious chemicals, predators, competitors of food
85
What do the signals that the cells receive elicit
appropriate responses
86
What are appropriate responses
moving towards or away from a cell
87
What is a signal
information that is detected by specific receptors and converted to a cellular response
88
What type of process is the response of a cell
chemical process
89
What is signal transduction
conversion of info into a chemical change
90
What is specificity
precise molecular complementary between the signal and receptor molecules
91
What mediates specificity
weak, non covalent forces
92
In multicellular organisms what else contributes to specificity
only certain cell types have certain receptors
93
What helps achieve sensitivity
high affinity
cooperativity
amplification
94
What helps aid high affinity
receptors have a high affinity for signal molecules, affinity is between ligand and the receptor
95
How is the affinity for the ligand and receptor expressed
Kd
96
What is Kd
dissociation constant
97
What helps aid cooperation
ligand receptor interaction, large changes occur in receptor activation with only small changes in ligand concentration
98
What is amplification
where a signal is amplified by an enzyme cascade
99
What is an enzyme cascade
the ligand binds to a receptor, activates an enzyme that is associated with the receptor, that enzyme activates multiple molecules of a second enzyme which also activates many molecules of another enzyme
100
How fast can an enzyme cascade produce a magnitude
milliseconds
101
Why must signals be terminated
so downstream effects are in proportion to strength of the original stimulus
102
What is modularity
interacting signaling proteins allow a cell to mix and match a set of signaling molecules to create complexes with different functions
103
What are scaffold proteins
proteins that have an affinity for several enzymes that interact in cascades and bring those proteins together
104
What do scaffold proteins ensure
interactions between proteins and enzymes occur at the right time and location
105
What is densitization
when a signal is constantly present the receptor system is desensitized
106
What occurs when the stimulus falls below threshold
the system becomes sensitized again
107
What is integration
the ability of a system to receive multiple signals and produce a unified response
108
What does integration allow
conversing to occur at several levels
109
What does integraiton help maintain
homeostasis
110
What are the 6 basic receptor types
```
g protein coupled
receptor tyrosine kinase
receptor guanyly cyclase
gated ion channels
adhesion receptors
nuclear receptors
```
111
What does GPCR stand for
Gprotein coupled receptors
112
What 3 components make up the G protein pathway
G-protein complex, transmembrane receptor, effector enzyme
113
What is the structure of the transmembrane receptor
binding site for ligand, 7 transmembrane helical segments
114
What occurs to the G protein to make it active vs inactive
The GDP gets swapped out for GTP to become active
115
Where is the effector enzyme located
within the membrane
116
What does the enzyme produce
the second messenger
117
What does the second messenger do
affects downstream targets
118
The human genome encodes how many GPCRs
350
119
What are orphan receptors
receptors that do not have their natural ligands identified
120
What do adrenergic receptors bind
epinephrine
121
What is epinephrine
fight or flight hormone, binds to the receptor in the membrane
122
What are the 4 types of adrenergic receptors
alpha1
alpha2
beta 1
beta 2
123
What defines the differences in the adrenergic receptors
their affinities and responses, location within different tissues
124
What is an agonist
structured analogs that bind to the receptor and result in a similar effect to the natural ligand
125
What is an antagonist
analogs that bind without triggering the normal effect and block agonists and natural ligands
126
Where are beta adrenergic receptors found
muscle, liver, adipose tissue
127
What do beta adrenergic receptors do
mediate changes in fuel metabolism and increase the breakdown of glycogen and fats
128
What is the structure of a beta adrenergic receptor
integral protein, 7 transmembrane helices of 20 to 28 AA
129
What is an alternative name for receptors with 7 transmembrane helices
heptahelical receptors
130
What does the binding of epinephrine to the receptor result in
a conformation change
131
Where does the conformational change occur
to the intracellular domain
132
What does the conformational change to the intracellular domain result in
promotes dissociation of GDP and binding of GTP
133
What occurs to the g protein subunit
it separates into complexes
134
What two complexes
beta gamma and then alpha
135
Which complex moves away to activate the next step
the GalphaS
136
What does the GalphaS complex activated
adenyly clyclase
137
What is adenyly cyclase catalize
cAMP
138
What is cAMP catalyzed from
ATP
139
What does cAMP do
activates protein kinase A
140
What does protein kinase A do
regulates downstream effects
141
G proteins that are composed of three parts are what
trimeric
142
What is the stimulatory protein for the G protein complex
alpha subunit
143
What is the structure of adenyly cyclase
integral protein of plasma membrane
144
How does GalphaS attach to the membrane
via covalently attached palmitoyl groups
145
What inactivates the G alpha unity
intrinsic GTPase
146
What does intrinsic GTPase do
self limits
147
What does Protein Kinase A do
phosphorylate Ser or Thr residues of target proteins
148
In its inactive state, what does protein kinase A structure
two catalytic subunitys and two regulatory subunits
149
When bound together, what is the strucure of PKA like
auto inhibitory domain of each subunit occupies the substrate binding cleft of catalytic domains
150
when cAMP binds to PKA R subunitys, what occurs
R moves out of catalytic domain and dissociates R and C subunits
151
What is a consensus sequence
neighboring residues needed to make Ser or Thr residue for phosphorylation
152
What are the 3 mechanisms that cause G protein termination
concentration of epinephrine
hydrolysis of GTP bound to G alpha subunit
remove 2nd messenger
153
How does the concentration of epinephrine lead to termination of G protein complex
when epinephrine drops belows Kd, the hormone dissociates from the receptor and resumes inactive conformation
154
How does inactivation through hydrolysis of GTP bound to G alpha subunit occur
GTPase activity occurs and GTP becomes GDP
155
How does removing the 2nd messenger inactivate complex
hydrolysis of cAMP to 5'AMP
156
What causes the hydrolysis of cAMP to 5'AMP
cyclic nucleotide phosphodiesterase
157
What does desensitization cause
dampening the response even when the signal persists
158
What mediates densitization
protein kinase that phosphorylates receptor on intracellular domain
159
What does Beta ARK do
phosphorylate Ser residues
160
What does BARK function
creates a binding site for Beta arrestin
161
What does beta arrestin do
prevents further interaction of receptor and G-protein
| facilitates receptor sequestration removal of receptors from membranes into vesicles
162
Can PKA move into the nucleus
yes
163
When PKA moves into the nucleus what does it do
phosphorylates CREb
164
What are adaptor proteins
proteins that hold together other protein molecules
165
What is the receptor tyrosine kinase family
large family of plasma membrane receptors with intrinsinc protein kinase activity
166
How do tyrosin kinase family receptors transduce extracellular signals
via the ligand binding domain and enzyme
167
Where is the ligand binding domain on the receptor
on extracellular side
168
Where is the enzyme domain on the receptor
intracellular side
169
How are the ligand binding domain and enzyme connected
by a single transmembrane segment
170
What is the enzyme of the tyrosine kinase family do
phosphorylate Tyr residues in specific target proteins
171
What is the type of enzyme in tyrosine kinase family
tyrosine kinase
172
What is the function of insulin
regulates metabolic enzymes and gene expression
173
Does insulin enter the cells
no
174
What does insulin do to change gene expression
initiates a signal that travels a branched pathway from PM to insulin sensitive enzymes in cytosol and nucleus
175
The units that make up the extracellular receptor are what
identical alpha subunits
176
What are the units that make up the intracellular receptor
identical beta subunits
177
the tyrosine receptor is made up of what
two alpha/beta monomers to make a dimer
178
which subunit has insulin binding domain
alpha
179
which subunit has kinase activity
beta
180
What does the tyrosine kinase do
transfers phosphate from ATP to hydroxyl group of tyrosine residues
181
each beta subunit phosphorylates what
3 tyrosine residues in beta subunit
182
What type of phosphorylation is this
autophosphorylation
183
What does autophosphorylation cause
opens up the active site so the enzyme can phosphorylate tyrosine residues of other target proteins
184
In the insulin what occurs first
autophosphorylation of INSR occurs
185
What is the target of INSR
insulin receptor substrate 1
186
What does INSR do to INRS-1
phosphorylates on several tyrosine residues
187
What occurs to the activated IRS1 molecule
becomes point of nucleation for complex of proteins that carry message from insulin receptor to targets in cytosol and nucleus
188
What does the phosphorylate tyrosine domain of IRS1 bind
SH2 domain of Grb2 protein
189
What is Grb2 protein
an adaptor protein
190
What does Grb2 protein have
SH3 domain
191
What does the SH3 domain bind
proline rich SOS that acts as guanosine nucleotide exchange factor
192
What does the guanosine nucleotide exchange factor do
replace bound GDP with GTP on Ras, a G-protein
193
What is Ras
a small family of G-proteins
194
What does Ras do
activates Raf-1
195
What is Raf-1
protein kinase
196
What does Raf1 do
activates MEK
197
What does MEK do
activates ERK
198
How are MEK and ERK activated
phosphorylation of both threonine and tyrosine residues
199
What does ERK do
enters nucleus and phosphorylates transcription factors
200
What does ERK phosphorylate
Elk1
201
What does Elk1 do
modulates 100 insulin regulated genes
202
What does insulin act as
growth factor
203
What family does ERK belong to
MAPK
204
What does MAPK stand for
mitogen activated protein kinase
205
What is mitogen
extracellular signals that induce mitosis and cell division
206
What family does MEK belong to
MAPKK
207
What family does Raf1 belong to
MAPKKK
208
What do MAPK, MAPKK, MAPKKK make up
the MAPK cascade
209
What functions as a branch in the insulin signaling pathway
PIP3 pathway
210
Where does the PIP3 pathway branch in the insulin signaling pathway
where the insulin receptor substrate 1 is phosphorylated
211
What interacts with IRS1 through its SH2 domain
PI3K
212
What does PI3K do
convert PIP2 to PIP3
213
What does the charged phosphorylated head protrude into
the cytoplasmic side
214
What attaches to PIP3
protein kinase B
215
What occurs to PKB when attached to PIP3
phosphorylated by PDK1
216
What occurs once PKB is phosphorylated
it phosphorylates Serine and threonine residues of glycogen synthase kinase 3
217
when phosphorylated by PKB is glycogen synthase kinase3 inactive or active
inactive
218
What does PKB trigger
clathrin aided movement of glucose transports from internal vesicles to PM
219
What terminates PI3K activity
PIP3 specific phosphatase
220
What type of kinase activity does the JAK STAT signaling system involve
tyrosine
221
In the JAK STAT signaling system, is there always kianse activity
no
222
When is there JAK STAT signaling system when is there kinase activity
when the ligand binds
223
When the ligand binds, what binds to give the receptor kinase activity
tyrosine kinase
224
Whay is a cytokine for JAK STAT system
erythropoeitin
225
Where is erythropoeitin produced
in kidneys
226
When the tyrosine kinase binds what occurs to the receptor
receptor dimerizes and activates JA kinase
227
What is the function of the JA kinase
phosphorylates Tyr residues in cytoplamic domains of EPO receptor
228
What are STATs
collection of transcription factors that are targets of JAK
229
STATs bind what
phosphorylate tyroside residues in EPO receptor
230
phosphorylates STATS move where
into the nucleus
231
What do phosphoylated STATs moving into the nucleus result in
transcription of specific genes
232
What can JAK also trigger
MAPK cascade
233
What are the general features of a receptor protein of enzyme
ligand binding domain or active site
| transmembrane segment
234
Under what conditions is insulin released
when blood glucose levels are high
235
What does signal transduction mean
converting information into a chemical signal to result in cellular responses
236
What is a hormone
a small chemcial molecule produced by various tissue types that bind to receptor to stimulate cell response. Hormones are produced by one cell and act upon another
237
What is the end product of most signals
phosphorylation for enzyme activation and inhibition
238
How do gated ion channels work
open or close in response to concentrations of signal ligand
239
How do receptor enzymes work
ligand binding to extracellular domain stimulates enzyme activity in intracellular domain
240
How do serpentine receptors work
external ligand binding to receptor activates GTP binding protein which regulates an enzyme
241
What is receptor with no intrinsic enzymatic activity work
interacts with cytosolic protien kinase which activates a gene regulating protein to change gene expression
242
How do adhesion receptors work
binds molecules in extracellular matrix and changes conformation thus altering its interaction with cytoskeleton
243
How do steroid receptors work
steroid binding to a nuclear receptor protein allows the receptor to regulate the expression of specific genes
244
What does a smaller Kd mean
has greater affinity for ligand and receptor
245
How is glycogen phosphorylase b activated by epinephrine
epinephrine binds
activates G protein
activates adenyly cyclase to produce cAMP
cAMP activates protein kinase A
PKA phosphorylates phosphorylase b
phosphoylase b phosphoylates glycogen phosphorylase b to become active
246
How is PKA regulated by cAMP
allosterically by binding at a site other than active site
247
WHat enzyme is responsible for the degradation of cAMP
cyclic nucleotide phosphodiesterase
248
What does cAMP become
5'AMP
249
What allows beta arrestin to bind
after Barr phosphorylates Serine residues of the carboxyl terminus of the receptor
250
When arrestin is bound to the receptor what occurs
the receptor enters cell via endocytosis
251
In the inactive state of the insulin receptor what is its arrangement and structure
an unphosphorylated tyrosine domain keeps the activation loop in a position that blocks substrate binding site
252
In active state what is structure of receptor
the negative aspartate groups nearby the phosphorylate tyrosine cause conformational change that moves the activation loop to move making room for target protein in substrate to bind
253
What is the signaling pathway for insulin
insulin binds to receptor
receptor undergoes autophosphorylation
receptor phosphorylates IRS-1 on Tyr residues
SH2 domain of Grb2 binds to IRS1, SOS binds to Grb2 and then to Ras
causes GDp release and GTP binding to Ras
Ras binds to Raf1/activates it
Raf1 phosphorylates MEK on serine residues
MEK phosphoryles ERK on threonine residues
ERK moves into nucleus
ERK phosphorylates Elk1
Elk1 joins SRF to stimulate the transcription of genes
254
What is the signaling pathway for glycogen synthesis
IRS1 activates PI3K (binds to SH2 domain)
PI3K converts PIP2 to PIP3
PKB bound to PIP3 is phosphorylated by PDK1
PKB inactivates GSK3
GSK3 cannot convert glycogen synthase to inactive form
synthesis of glycogen is accelerated
PKB stimulates movement of glucose transporter to PM
255
What is PIPs
cell membrane lipids
