PDF's Flashcards
(218 cards)
1
Q
Cytogenetic analysis of cells from retinoblastomas showed that the region around
chromosome _____ often had an abnormal structure
A
13q14
2
Q
The Rb protein is ______ in rapidly proliferating cells at S or
G2 of the cell cycle, but is _________ in non-proliferating cells in G0 of G1 of the cell
cycle.
b
A
hyperphosphorylated
hypophosphorylated
3
Q
The hypophosyphorylated form of the RB protein functions to ____
A
repress cells into the S phase
4
Q
RB protein is an oncogene or tumor suppressor?
A
TS
5
Q
What phosphorylates the RB protein?
A
CDKs
6
Q
The RB protein is a target for many animal tumor viruses such as
A
SV40 and HPV
viruses drive a quiescent cell into the S phase
of the cell cycle and to proliferate by producing a viral protein(s), SV40 T antigen (T stands for
transforming) or HPV E7 protein, that binds to and inactivate the RB protein.
7
Q
The ____ gene is a tumor surpessor in Familial Adenomatous Polyposis (FAP)
A
APC
8
Q
Incidence of FAP
A
1/10,000
9
Q
The APC gene is on chromosome ___
A
5q
10
Q
The APC gene encodes a cytoplasmic protein that regulates the localization of ____-
A
beta catenin
11
Q
beta catenin is kept at the plasma membrane by being bound to ___ in normal cells
A
E-cadherin
12
Q
When the APC is lost in FAP patients, ________________.
A
Beta-catenin goes to the
nucleus to produce transcription of oncogenes like c-myc
13
Q
ICF and ECF: Na+
A
ICF: 14 mM
ECF: 140 mM
14
Q
ICF and ECF: K+
A
ICF: 145 mM
ECF: 5 mM
15
Q
ICF and ECF: Cl-
A
ICF: 5 mM
ECF: 145 mM
16
Q
ICF and ECF: A-n
A
ICF: 126
ECF: 0
17
Q
ICF and ECF: H20
A
ICF and ECF: 55,000 mM
18
Q
Osmolarity
A
the total concentration of solute particles: for example, a 1 M solution of CaCl2 gives a 3 osM solution (3 solute particles/molecule dissolved).
19
Q
Nernst equation
A
E=-60/(valence elections)*log([ ]o/[ ]i)
20
Q
Driving force of an ion
A
difference between Vm and Eion
21
Q
3 SNARE proteins
A
VAMPs
Syntaxin
SNAP25
22
Q
Structure of VAMPs
A
transmembrane domain at one end with a helical domain in it
23
Q
Structure of Syntaxin
A
transmembrane domain with helical domain
24
Q
Structure of SNAP25
A
No TM domain, two helical domain, fatty acid binding region that acts like a membrane binding domain
25
All vesicles contain _____, while all target membranes contain _______ and ______.
VAMPs
| Syntaxin and SNAP25
26
Enzyme that regulates dissociation of SNARE proteins
NSF protein (hexamer that uses 6 ATP to for a barrel and twist)
27
Refolding of syntaxin is mediated by ____
Sec1
28
Main primary active transporters
NA/K
CA++
H+
29
Two basic types of secondary active transporters
Cotransporters- same direction
| Antiport or exchange- opposite direction
30
Examples of cancers inherited in autosomal dominant fashion
Familial adenomatous polyposis
familial retinoblastoma
Familial breast and ovarian cancer
Wilms tumor syndromes
31
Examples of cancers inherited in autosomal recessive fashion
xeroderma pigmentosa
ataxia-telangiectasia
bloom's syndrome
Fanconi's anemia
32
Function of HPV E7 protein
bind and inactivate the RB protein
33
Sporadic cases of retinoblastoma are usually ______
unilateral
| unlikely to occur in both retinas
34
BRCA2 is allelic with _____
the Fanconi's anemia D1 gene, FANCD1
35
"Hotspots" in p53 mutations
Certain p53 point mutations are found more frequently than others in human cancers. These mutations are called “hotspots
36
Viruses that inactivate p53 (and also Rb)
Adenovirus E1B
| HPV E6
37
The retroviral RNA genome consists of ______
two identical strands held together by a tRNA molecule
38
```
In a retrovirus:
gag encodes for ___
env for ____
pol for _____
v-onc
```
internal virion proteins
virus membrane glycoproteins
virus polymerase
v-onc gives ability ro rapidly proliferate and form tumors
39
4 examples of v-onc's
v-src: rous sarcoma virus
v-erb: avian erythroblastosis virus
v-abl: Abelson leukemia virus
v-myc: usually fused to gag gene, neoplastic transformation of cells
40
The products of oncogenes typically mimic
hormones or growth stimulating factor
41
The proto-onc or c-onc genes are involved in _______. What type of changes are responsible for these effects?
The proto-onc or c-onc genes are involved in spontaneous malignancies that have nothing to do with a retrovirus.
Either quantitative changes (too much protein) or qualitative changes (overactive or unregulated protein) in the proto-oncogene are responsible for these effects.
42
Difference between c-src and v-src
c-src has a different carboxy-terminal amino acid sequence that v-src and has numerous introns that do not exist in v-src
43
Difference between c-myc and v-myc
c-myc also has many introns not present in v-myc, although the coding sequences are nearly identical (7 amino acid changes
44
Human bladder cancer mutation
c-ras
45
Oncogene found in neuroblastomas
N-myc
46
Oncogene that codes for an integral membrane protein kinase that is amplified in about 20% of breast cancers
erbBw or HER2/neu
47
monoclonal antibodies specific for the protein product of the HER2/neu/erbB2 oncogene
Herceptin
48
Why do drugs that inhibit “normal” cellular proteins (c-myc, c-abl, etc.) kill only the cancer cells?
cancer cells but not normal cells have become dependent or “addicted” to the overexpressed oncogene. This referred to as “oncogene addiction
49
Diagnostic criteria for LFS (3)
* A probandwith a sarcoma diagnosed before 45 years of age AND
* A first-degree relative with any cancer under 45 years of age AND
* A first-or second-degree relative with any cancer under 45 years of age or a sarcoma at any age
50
How do you test for LFS?
Direct sequencing of p53 (either only hotspots or entire gene)
51
The major causes of death in patients with VHL are_______ and________
Metastatic RCC
| CNS hemangioblastomas
52
Von Hippel-Lindau disease is classified based on presence or absence of _________ and type of ___________.
Pheochromocytoma (adrenal gland tumor)
| VHL mutation
53
Type 1 VHL disease is due to ____
total or partial loss of VHL
54
Type II VHL disease is due to
VHL missense mutation
55
VHL chromosomal location
short arm of chromosome 3
56
Actions of VHL protein
Regulation of HIF
suppression of aneuploidy
maintenance of primary cilia
stabilization of macrotubules
57
HIF-alpha is hydroxylated by
proline and asparagine hydroxlase
58
Hydroxylated HIF-alpha is___
ubiquinated by WT VHL and undergoes proteosomal degredation
59
When VHL is mutated HIF ____ and activates ____ (4)
accumulates
| VEGF, PDGF, TGF alpha and Beta
60
3 classes of lipids in a membrane
phospholipids
sphingolipids
cholesterol
61
Two important properties of channels
1. most are selective
| 2. some channels contain molecular gates
62
The "patch clamp" technique is used to _____
see individual ion channels at work
63
molecules can cross membranes through _____ or ______
channels or transporters
64
3 mechanisms to solve problem of volume contro (due to movement of water)
1. make cell impermeable to water
2. build a strong wall around cell
2. balance the osmotic force osmotically
65
What does the Van't Hoff equation tell you?
quantitative relationship between osmotic suction and the pressure one has to exert in order to balance it
66
Solution that makes a cell shrink
hypertonic
67
Solution that makes a cell swell
hypotonic
68
Time course of volume change when immersed in 600 mosM glycerol (+) with 300 Anion in cell
Cell will initially shrink but will later fill with water and burst
69
What does the Nernst equation tell you?
Equilibrium potential
70
What does the membrane potential depend on?
Relative permeability
71
What is the driving force of a cell?
the difference between Vm and Eion
72
Causes of hyperkalemia
Injuries that disrpt cell membranes
| attack of red blood cells
73
Diagnosis of hyperkalemia
EKG to detect arrhythmias
74
Treatment of acute hyperkalemia
C BIG K
| Calcium, Bicarbonate, Insulin + Glucose, Kayexalate
75
What does Kayexalate do?
Ion exchanger- gives up sodium for potassium ions
76
In regards to Inflammatory Bowel disease, smokers are at increased risk for ______
Crohn's disease
77
In regards to IBD, former smokers and nonsmokers are at increased risk for_____
ulcerative colitis
78
Fistulas are ____ in Crohns but ____ in UC
common
| rare
79
Inflammation is _____ in Crohn's and _____ in UC
transmural
| mucosal
80
Pattern in Crohn's vs. UC
discontinuous vs continuous
81
Hematochezia (blood in stool) is ____ in Crohn's but ____ in UC
rare
| common
82
Location of Crohn's vs. UC
Ileum vs Rectum
83
Mechanism of insulin release
: glucose enters the cell through the GLUT2 transporter, undergoes glycolysis, leading to an increase in the intracellular ATP to ADP ratio. This change closes the ATP-sensitive potassium channel, preventing outward leak of potassium ions. The resultant buildup of intracellular potassium (because there are other sodium/potassium channels actively antiporting against the gradient) depolarizes the membrane, activating a voltage-gated calcium channel and leading to calcium influx. The increased intracellular calcium ion concentration leads to exocytosis of preformed insulin-containing secretory granules
84
Half life of insulin
5 minutes
85
Two cardinal sins of DKA management
Prematurely stopping insulin infusion
| Failing to use enough dextrose
86
How does dehydration occur in DKA?
Excess glucose in filtrate-> kidney cannot absorb as much water
87
Mechanism of potassium depletion in DKA
aldosterone released in response to dehydration-> sodium is retained at the expense of potassium ions
88
Despite the fact that a DKA patient may present with hyperkalemia, they will have _____.
low potassium levels in cells and have greater potassium needs
89
Cerebral edema in DKA clinical manifestations
mental status changes; headache; Cushing’s triad (hypertension, bradycardia, irregular respirations); or fixed, dilated pupils
90
Treatment of cerebral edema in DKA
elevate head of bed
hyperventilating the patient
giving IV mannitol (not metabolized) or hyertonic saline
91
Glucose transporter
Example of facilitated diffusion
transport glucose in either direction while burning no energy
Once in the cell, glucose in phosphorylated to G-6-P
92
What pump is responsible for moving calcium out of the cell
Na/Ca pump
93
Digitalis
extract that can help the heart beat stronger by blocking the Na/K pump and indirectly inhibitinf the Na/Ca exchanger
94
Na/H exchange carrier
secondary active transport system, in which the inward leak of Na+ drives the outward pumping of H+.
95
What pump bring chloride ions to the ICF?
Na/K/2Cl
96
While certain studies suggest the existence of a _____ pump, it likely does not exist.
H/K
97
Voltage gated channels of the KV, NaV and CaV families have______ membrane-spanning domains, each of which contains _________
4
| 6 alpha helices (S1 through S6)
98
_____ helices have ______ at every ______ position that sense voltage
S4
positively charged residues (lys or arg)
third position
99
The "P loop" between ____ and ____ helices forms the _____
S5 and S6
| ion conducting pathway
100
Neurotransmitter receptors directly coupled to ion channels
Ionotropic
101
Examples of an ionotropic receptors (2)
pentameric ligand gated channels
| Ionotropic glutamate receptor
102
Pantameric ligand gated channels are _____ and contain _____. _____ is the alpha helix that assembles around the central ion conducting pathway.
heteropentameric
4 transmembrane alpha helices (M1-M4)
M2
103
Ionotropic glutamate receptors are ____
tetrameric ligand gated channels
| NMDA receptors
104
NMDA receptors bind:
two of the four subunits bind glutamate and the other two bind glycine.
105
Chloride channels (CLC family)
dimer- each su has an ion permeation pathways
106
Aquaporin water channel
tetramer w 4 water pores and a central pore
107
Rank selectivity between the following channels: Na, K, Ca, nicotinic AChR
K > Na > Ca > nicotinic
108
In regards to epithelial cells, the Na/K pump is ALWAYS located on the _____ membrane and is the driving force for nearly all transport
basolateral
109
The apical membrane is ______ to sodium
highly permeable
110
TransPD = Vm (_____) – Vm (______)
basolateral
| apical
111
The key to understanding epithelial secretion in general and the main defect in those diseases is a _______ channel in the ________ membrane. in a resting cell this channel is _____
chloride
apical
closed
112
What activates the Cl channel on the apical membrane of epithelia?
in GI tract- digestion
| Pathogens (cholera)
113
Most important chloride channel on the apical membrane of epithelia
Cystic fibrosis transmembrane conductance regulator (CFTR)
114
Most important function of the kidney
get rid of non-volatile wastes
115
How does the kidney get rid of extra water?
hypothalamus stops secreting vasopressin-> removes aquaporins from apical membranes
116
What determines the threshold voltage in an action potential?
The point at which sodium and potassium CURRENTS are exactly equal and opposite
117
What is gained by having voltage-gated potassium channels?
Faster repolarization
118
Two types of refractory periods
Absolute
| Relative
119
What is accommodation mean in regards to action potentials?
If an axon is depolarized slowly, it may fail to generate an action potential, even if depolarized beyond what had been threshold for a rapid depolarization. In other words, the axon accommodates to the slow, steady stimulus
120
What is the safety factor in regards to action potentials and why is it important?
axons have more than enough Na channels to do the job; their safety factor of transmission is 5-10 times the minimum required for successful propagation.
Important for: branching of axons, speed of transmission
121
small diameter fibers have ____ threshold to external stimulation, conduct action potentials at ____ velocities, and have ____ safety factor for conduction.
High
lower velocities
low
122
Pain fibers have ____ diameters
small
123
Strongly associate allele in MS
HLA-DRB1
124
Virus and MS
EBV- infection late in life is bad
125
Drug that improves walking in MS patients
Dalfampridine
126
The typs of Nups
membrane anchored
scaffolding
barrier
127
Barrier Nups contain regions enriched in _____
phenylalanine/glycine repeats
128
NLS
rich in lysine
129
NES
Rich in leucine
130
NTF2
specific transporter for Ran GDP
131
NXF1/NXT1
transporters for mRNA and Ribosomal RNA
132
Low Ran GTP levels in ____
Cytoplasm
133
High Ran GTP levels in _____
nucleus
134
Six major functions of the ER
(1) synthesis of lipids (phospholipid, ceramide, and cholesterol; primarily in the smooth ER), (2) control of cholesterol homeostasis (cholesterol sensor and synthesis), (3) storage of Ca+2 (rapid uptake and release), (4) synthesis of proteins on membrane bound ribosomes (rough ER), (5) co-translational folding of proteins and early posttranslational modifications, and (6) quality control.
135
Protein that recognizes ER signal sequence
Signal recognition particle (SRP)
136
Chaperone protein involved in ER lumen
BiP
137
Type I membrane protein
amino terminal in ER lumen
138
Importance of N linked glycosylation
1. keeps proteins from aggregating
| 1. monitor unfolded proteins
139
Major functions of Golgi (4)
(1) Synthesis of complex sphingolipids from the ceramide backbone, (2) Additional post-translational modifications of proteins and lipids (most notably, glycosylation and sulfation), (3) Proteolytic processing, (4) Sorting of proteins and lipids for post-Golgi compartments.
140
Sulfation occurs where in the Golgi?
trans Golgi and trans Golgi network
141
Two major routes of endocytosis
1. phagocytosis
| 2. pinocytosis
142
Phagocytosis is carried out by ____ and _____
macrophages and neutrophils
143
Pinocytosis is usually associated with specific uptake of ____ and _____
ligands and receptors
144
Vesicles involved in endocytosis are typically formed by ____ or _____
clathrin coat proteins or caveolae
145
LDLRs are clustered on the membrane because ___
an adaptor protein complex AP2 binds the receptor and also binds clathrin
146
Caveolae are small endocytic vesicles that form ______
without coat proteins
147
Caveloae are especially important for membrane domains know as ____
Lipid rafts
148
Protein for caveolae formation
Caveolin
149
Each caveolae structure contains how many caveolin
144
150
The UPS is responsible for ____ degradation
rapid
151
Autophagy is mainly involved in degradation of _____ protein
long-lived
152
Enzyme in ER that allows formation of disulphide bonds
ERp57
| thiol oxidoreductase
153
Proteins in the ER involved in holding misfolded proteins there until they are properly folded
calnexin (TM) and calrericulin (Soluble protein in ER lumen)
154
Calnexin and calreticulin bind proteins if there is a ___ attached
Glucose
155
After one round of calnexin/calreticulin, glucose is removed. If not correctly folded ___ adds glucose back on
glucosyltransferase
156
The proteasome cuts up polypeptides into ____ AA segments
short 7-9 AA
157
the _____ of the proteasome is where proteolytic cleavage takes place
central cylinder
158
Th two caps of the proteasome recognizes ____ and uses ____ to unfold the protein
Polyubiquitin
| ATP
159
Three ligase enzymes involved in ubiquination
E1. E2, and E3
160
A chain of ___ ubiquitins is needed for proteosomal degradation
4
161
Interferon gamma induces transcription of
three novel beta subunits for proteasome (form immunoproteosome)
162
pH of lysosome
5
163
___________ plasma membrane proteins are targeted for endocytosis and are transferred via the late endosome/multivesicular body to the lysosome for degradation.
monoubiquinated
164
Necrosis
Mitochondria swell-> starve cell of ATP-> plasma membrane's opn pumps fail-> water fills cell-> cell bursts
Intensely proinflammatory
165
Defining morphologica feature of apoptosis
Collapse of nucleus
Chromatin becomes super condensed
Cells shrink
166
An apoptotic cell tears itself apart into ____
apoptotic bodies
167
Cell that eats apoptotic bodies
phagocyte
168
Why is a phagocyte important?
ensure that the apoptotic cell gets taken up by a healthy cell, before it has had a chance to spill its dangerous, proinflammatory contents.
169
Apoptosis in cells is accompanied by changes in which phospholipid in the plasma membrane?
PS
170
What happens to PS in an apoptotic cell?
Scramblase exposes it on the cell exterior
171
What happens when PS is exposed on the cells exterior?
Phagocytic cells recognize and digest cell
172
A macrophage recognizes an apoptotic cell and releases ____, which is anti-inflammatory. Thus, removal of apoptotic cells is ___
TGFB
| silent
173
low-dose radiation _____ lymphocytes; rather, it ______
does not kill
| induces them to kill themselves
174
Normally the mitochondrial membrane is guarded by
Bcl-2 and Bcl-Xl
175
When a cell receives an apoptotic signal ___ and ____ make the mitochondrial membrane permeable to _____
Bax and Bak
| cytochrome C
176
Proteins that replace Bcl-2 and Bcl-Xl during apoptosis
Bim and PUMA
177
Cytochrome C activates ____, which activates _____, which activates ______
Apaf-1
Caspase 9
Caspase 3
178
Caspase 9 is a ___ caspase, while caspase 3 is an ___
signal
| executioner
179
_____ are responsible for surveillance of the surfaces of all body cells.
Cytotoxic (killer) T cells (CTL)
180
CTL-> ___-> which then_____-> ______-> ____-> ____
```
upregulates FasL
engages and cross links with Fas or CD95
CD95 activates FADD
Caspase 8
Caspase 3
```
181
autoimmune lymphoproliferative syndrome (ALPS) mutation
Fas or FasL
182
Protein related to Caspase 8 that competes with FADD and inhibits apoptosis
FLIP
| viral form in herpes
183
In the other CTL mechanism, the killer cell secretes ____ and a _______ that together deliver apoptosis-inducing molecules to its intended target
granzymes
| pore making protein (perforin)
184
Why are lymphocytes so susceptible to radiation?
a damage lymphocyte can lead to autoimmunity or lymphoma
185
Example of receptor family karyopherins
karyopherin beta
| interacts directly with cargo and FG Nups
186
Example of adapter Karyopherins
karyopherin alpha
| have specific binding sites for specific cargos and receptor family karyopherins
187
Specific transporter for Ran GDP
NTF2
188
Transporters for mRNA and rRNA
NXF1/NXT1
189
____ relieves binding affinity for Ran-GTP/Karyopherin binding, allowing _____ to activate Ran's intrinsic GTPase
Ran BP1
| RanGAP1
190
Durin RanGTP facilitated export ____ exchanges GTP for GDP
NTF2
191
Cholera exhibits >____ serogroups including ____
>200
| O-specific polysaccharide (OPS) of LPS
192
The ___ of cholera supports colonization.
Pili (TCP)
193
The cholera toxin subunits
1 alpha
| 5 beta
194
Receptor of cholera toxin
ganglioside GM1
195
Cholera toxin increases ____ production, which induces the ____ to secrete ____
cAMP
CFTR
Cl-
196
Patients with blood group ____ are more susceptible to severe cholera infections
Blood group O
197
3 main types of autophagy
1. macroautophagy
2. microautophagy
3. chaperone mediated autophagy
198
Autophagy is induced during times of ____
nutrient stress
199
You can monitor autophagy by attaching GFP to ____
LC3
200
Genes that regulate autophagy
Atg
| Very "druggable"
201
Why can you not always be certain that an observed effect was autophagy related when you knockout an ATg gene?
All known autophagy regulators also do other things independent of autophagy
202
Autophagic process
1. induction
2. vesicle nucleation (phagophore)
3. V expan (omegasome)
4. cargo transporting (LC3 and p62)
5. vesicle closure (autophagosome)
6. V fusion with endosome (amphisome)
7. V fusion with lysosome (autolysosome)
203
If Beclin 1 binds to Bcl-2/Bcl-Xl->
No autophagy
204
Beclin-1 interacts with BCL-xl via a ___ domain
BH3
205
BH3 mimetic that disrupts Beclin-1-Bcl-xl interaction
ABT 737
206
Rapamycin ____ autophagy
increases
207
AA recognition sequence in chaperone mediated autophagy
KFERQ
208
Describe rationale behind autophagy’s protective action against neurodegeneration
Autophagy degrades the aggregate-prone proteins (perhaps after they have started to form small aggregates).
209
IV insulin 2 purposes in treatment of DKA
```
decrease blood glucose
halting ketoacidosis (takes longer)
```
210
Insulin actions in liver (4)
+ glucose uptake, glycogen synthesis
- gluconeogenesis
- ketogenesis
+lipogenesis
211
Insulin actions in muscle (2)
+ glucose uptake, glycogen synthesis
| + protein synthesis
212
Insuliin actions in adipose tissue (3)
+ glucose uptake
+ triglyceride uptake
+ lipid synthesis
213
3 types of cytoskeleton fibers
microtubules
actin
intermediate filaments
214
Domains in microtubules
alpha, beta, and gamma
215
2 steps in microtubule formation
1. Heterodimer formation
| 2. protofilaments binding to one another
216
Polymerization of microtubules is on the ____ end
plus
217
The ___ cap on the plus end of microtubules stabilizes them
GTP
218
Microtubule severing protein mechanisms (2)
GTP-> GDP
| or cut them
