Unit 1 Deck 4 Flashcards
1
Q
In what phase of the cell cycle are G1 cyclins made?
A
G1
2
Q
DNA damage leads to increased synthesis of what protein?
A
p21, a cdk inhibitor
3
Q
Cells can be stimulated to divide by activation of cell surface proteins, including adhesion molecules like integrins, to activate what?
A
MAP kinase pathway
4
Q
MAP kinase activity increases what in the cell
A
The MAP kinase pathway increases cyclin subunits and blocks p21 and p27, both related cdk inhibitors.
5
Q
What protein must be phosphorylated and degraded to access the origin recognition complex in S phase?
A
Cdc6
6
Q
In what stage of the cell cycle are histones made?
A
S phase
7
Q
In G2 phase, what must be done to histones to initiate condensation?
A
Phosphorylation
8
Q
What two proteins help the chromosomes complete condensation and at what stages of the cell cycle do they become active?
A
Cohesins - added during G2 - link replicated sister chromatids until anaphase
Condensins - added during M - help package chromosomes
9
Q
The onset of mitosis is controlled by __1__ in the __2__.
A
- kinase activity
2. cytoplasm
10
Q
When are additional centrioles synthesized?
A
In S phase, but do not separate and become their own centrosome until mitosis.
11
Q
What is the theme of prophase?
A
Chromosome condensation
12
Q
What is the theme of prometaphase?
A
Breakdown of the nuclear envelope
Chromosomes attach to spindles.
13
Q
Unattached microtubules in the spindle are called:
A
Astral MT’s
14
Q
MT’s that attach to other MT’s in the mitotic spindle are called:
A
Polar MT’s
15
Q
MT’s that suspend chromosomes on the metaphase plate are called:
A
Kinetochore MT’s
16
Q
At mitosis, another name for the centrosome is the:
A
Spindle pole
17
Q
Separation of sister chromatids is inhibited until:
A
All chromosomes achieve bipolar attachment.
18
Q
What is the official trigger for entering anaphase?
A
Tension on the kinetochores inhibits the kinase and they don’t separate.
19
Q
What is the difference between Anaphase A and Anaphase B?
A
Anaphase A - kinetochore MT’s are shortening, pulling apart sister chromatids
Anaphase B - poles start to move apart
20
Q
What are the functions of kinesin and dynein during anaphase B?
A
Kinesin pushes from the middle of the spindle. Dynein pulls at the ends.
21
Q
At what stage of mitosis does the nuclear membrane reform?
A
Right after anaphase, and completes during telophase
22
Q
In telophase, the division of the cytoplasm begins with the assembly of the:
A
Contractile ring
23
Q
The contractile ring is made of:
A
Actin filaments
24
Q
Cytokinesis is achieved by:
A
Myosin and actin, myosin II sliding along the MF’s, constricting the new cells.
25
What is the function of cytochalasin?
Blocks actin assembly, if given to a mitotic cell, it will not undergo cytokinesis.
26
What is the function of the drug vincristine?
Disrupts MT assembly, cancer tx
27
What is the fx of the drug taxol?
Stabilizes MT's to prevent further growth, cancer tx
28
What is a cyclin dependent kinase?
A serine or threonine-specific protein kinase that has no activity unless combined with a matching regulatory cyclin subunit
29
What are the steps of cdk activation?
1. Mitotic cdk finds M-cyclin, they attach.
2. Inhibitory kinase Wee1 AND activating kinase Cak phosphorylate their respective sites on the cdk.
3. Activating phosphorylase Cdc-25 removes the inhibitory phosphate on cdk 21.
30
How is cdc25 phosphatase involved in a positive feedback loop?
Cdc25 is activated by an activated M-cdk, which then activates an M-cdk...etc...
31
When Cdk activity is no longer needed, what are the steps in inactivation?
1. Cyclin is ubiquitylated by an E3 ubiquitin ligase, thereby targeting the protein for destruction by a proteasome.
2. The final (activating) phosphate is removed from the cdk.
32
What is the APC, anaphase promoting complex?
An E3 ubiquitin ligase that
(1) turns off the M-Cdk at the transition from metaphase to anaphase
(2) activates a protease called separase which promotes chromosome separation
33
What protein cleaves cohesins at the metaphase/anaphase junction?
Separase
34
What would stop entry into S phase from G1? Name 2 things.
1. Unfavorable extracellular environment
| 2. Damaged DNA
35
What would stop entry from S phase to G2 phase? Name 1 thing.
Damaged or incompletely replicated DNA
36
What would stop entry from G2 phase into M? Name 1 thing
Damaged or incompletely replicated DNA
37
What would halt M phase? Name 1 thing.
Chromosome improperly attached to mitotic spindle.
38
What are the steps in activation and function of p53?
1. DNA damage detected, cell cycle arrested to synthesize p53
2. p53 activated by phosphorylation
3. activated p53 binds to regulatory region of p21 DNA, p21 is transcribed and translated
4. p21 attaches to cyclin-Cdk complex and inactivates it
39
Name the three major cell cycle checkpoints:
G1/S
G2/M
metaphase/anaphase in M
40
The kinase that phosphorylates the retinoblastoma gene, allowing E2F-dependent transcription, can best be described as:
A proto-oncogene.
41
What is the MOA of the glycopeptides (vancomycin):
The glycopeptides bind to the substrate of the transpeptidation enzyme and disrupt cell wall construction.
42
What is the MOA of the penicillins?
Penicillins prevent cross-linking of peptidoglycan sheets. (Pop!)
43
What is the MOA of most fluoroquinolones IF the target is a gram-negative bacteria?
DNA gyrase, inhibition of relaxation of supercoiled DNA
44
Name the 4 functions of the Golgi.
1. Sorting/dispatching station
2. Modification of N-linked oligosaccharide chains on glycoproteins made in the ER
3 synthesis of O-linkedoligosaccharides on proteins and lipids made in the ER.
4. synthesis of GAG chains for proteoglycans
45
Where is the Golgi usually located?
Near the nucleus.
46
Both the cis and trans networks are involved in:
Protein sorting
47
Each Golgi cisterna contains its own:
Processing enzymes
48
Modification of N-linked oligosaccharides is carried out by what 2 main Golgi enzymes?
1. Glycosidases
| 2. Glycosyl transferases
49
The degree of modification of proteins in the Golgi can vary to produce diverse N-linked oligosaccharides which have been divided into 3 main classes:
1. High mannose
2. Complex
3. Hybrid
50
What is O-linked glycosylation?
The *covalent* attachment of sugars to the OH groups of serine or threonine residues. Occurs in the Golgi.
51
Which kind of sugar addition is post-translational?
O-linked glycosylation
52
How are proteoglycans and glycoproteins different?
Proteoglycans - mostly sugar, usually >95% carbs by mass
| Glycoproteins - mostly protein, they DO NOT contain repeating units
53
What do glycoproteins always have?
GAGs, glycosaminoglycans
54
What is a GAG?
A GAG is a linear polymer os repeating disaccharide units - uronic acid-hexosamine, that are 100's of sugars long.
55
Heparin is a kind of:
GAG, there are 6 classes!
56
Where are proteoglycans synthesized?
The Golgi
57
What protein is responsible for creating GAGs on the initial core protein?
Glycosyltransferases specifically intended for this job
58
Where are proteoglycans and glycoproteins degraded?
Lysosomes, by proteases and glycosidases
59
What is the function of an endoglycosidase?
To remove the carb from the core protein, step 1 in proteoglycan/glycoprotein degradation in the lysosome.
60
Cell surface antigens, like the ABO blood group antigens, are made of:
Glycoproteins
61
Glycoproteins carry out MAJOR functions in the body! Name 7.
1. ECM structures
2. Hormones, ie FSH
3. Cell surface antigens, is ABO blood grouping
4. Plasma proteins, ie blood clotting factors
5. Immunologic molecules, ie immunoglobulins
6. Enzymes, ie proteases
7. Lubrication and protection, ie mucus secretions in GI
62
Mucins are a special class of:
O-linked Glycoproteins
63
The most abundant macromolecules in mucus are ___1___ which are typically secreted by specialized cells within the ___2___.
1. mucins
| 2. epithelium
64
The polymerization and high density of ___1___ in mucus allows these glycoproteins to generate a ___2___ and makes them resistant to ___3___.
1. carbohydrates
2. hydrated gel
3. proteases
65
GalNAc is associated with what allele?
A allele
66
Gal is associated with what allele?
B allele
67
Individuals with AB blood can donate to:
Only other AB individuals
68
The regulated (non-default) pathway of exocytosis is found only in:
specialized secretory cells, such as those that secrete large quantities of hormones or digestive enzymes.
69
In regulated exocytosis, what is necessary for fusion of the vesicles to the plasma membrane?
Only in response to an extracellular signal
70
What two kinds of WBC's participate in phagocytosis?
Neutrophils
| Macrophages
71
Fun fact!
Macrophages ingest more than 100 BILLION senescent red blood cells PER DAY!
72
Cells import cholesterol by
Receptor mediated endocytosis
73
Most blood cholesterol is transported as:
Low density lipoprotein (LDL)
74
What are the steps in the uptake of cholesterol.
1. Cholesterol is needed, cells synthesize receptors for RME and insert into PM.
2. LDL fuses with its receptor and is endocytosed.
3. Vesicle fuses with early endosome, and lowering pH dissociates LDL from receptor.
4a. Receptor recycled to PM.
4b. LDL continues to lysosome, where it is cleaved and becomes free cholesterol.
5. Cholesterol is released into the cytosol for use in membrane synthesis.
75
What is the defect in familial hypercholesteremia?
LDL receptors defective
| LDL builds up in blood
76
Receptor-mediated endocytosis can be exploited by __1__ to gain entry into a cell.
Viruses, ie used by HIV and influenza
77
Where are late endosomes located?
Usually near the nucleus.
78
What is "receptor-down regulation"?
When the receptor is degraded along with its ligand, in RME. Leads to a decrease in those receptors on the PM.
79
Transcytosis occurs in:
Transcytosis is the delivery of cargo/receptors in RME in polarized cells, ie travel in early endosomes from the basolateral to apical membranes.
80
How do lysosomes maintaintheir low pH?
Proton pumps maintain physosomes at a pH around 5!!
81
How do membrane proteins of lysosomes protect themselves from degradation by the low pH in the lumen?
They are heavily glycosylated, as are the enzymes in the lumen.
82
Nascent lysosomal hydrolases are tagged with:
Mannose-6-phosphate (M6P) marker, recognized by receptor in trans-Golgi, allows for specific transport to the lysosome.
83
Give an example of autophagy.
The removal of expanses smooth ER in liver cells following processing of a high toxic dose (ie too much alcohol).
84
What is the defect associated with Hurler syndrome?
Defect in enzyme required for GAG degradation
| Progressive cellular damage ensues
85
What is the defect associated with Schindler disease?
Defect in enzyme needed for oligosaccharide degradation, phenotypes vary considerably depending on what enzyme is affected
86
What is the defect associated with Gaucher or Tay-Sachs disease?
Defect in enzyme responsible for sphingolipid degradation
87
What is the defect associated with Inclusion cell (I-cell) disease?
Defect in enzyme responsible for generating M6P marker, therefore hydrolases are sent out of the Golgi via the default pathway, almost all hydrolytic enzymes are missing from lysosomes
88
What is a glycosidic bond?
Bond between 2 sugars
89
True or False: Glycosyltransferases transfer preformed oligosaccharides to the growing sugar.
False! Gylcosltransferases move 1 sugar at a time from e nucleotide to the growing sugar. **Oligosaccharyltransferases move larger sugars from lipid anchors to the growing sugar (Asn residue in ER)
90
The targeting of newly synthesized enzymes to mitochondria involves which transport mechanism?
Transmembrane transport
91
What is the role of the signal recognition particle RECEPTOR in protein targeting to the ER?
To release the SRP from the ER targeting signal
92
Name 5 intracellular bacteria.
1. Neisseria (cocci)
2. Enterics (Shigella, Salmonella, E. Coli, Yersinia)
3. Mycobacter
4. Chlamydia
5. Listeria
6. Legionella
7. Rickettsial (Rickettsia, Erlicihia, Anaplasma, C. burnetti)
8. SOME bacilli (B. anthracis)
93
What are the two obligate intracellular bacteria?
1. Rickettsia
| 2. Chlamydia
94
What are 3 pathways for surviving endocytosis?
1. Escape endosome
2. Subvert endosome and prevent it from fusing with lysosome
3. Survive lysosomal fusion (virulence factors that neutralize pH)
95
What are two trojan horse infections?
1. Mycobacter, TB
| 2. Enteric, typhoid
96
What kinds of bacteria has actin tails and can propel themselves from one cell to another? (Actin rockets)
Listeria
| Shigella
97
What is shigella's mechanism of infection?
```
Enters through M cells in gut
infects macrophages
travels to other side of the gut
enters neighboring cells, Act A virulence factor
local infection
```
98
What antibiotics are contraindicated in pregnancy?
Tetracyclines (doxy), instead use azithromycin or chloramphenicol
99
Give three characteristics of Listeria monocytogenes
1. Infects through contaminated food
2. Gram + rod
3. Beta-hemolytic
4. Tumbling motility
5. Grows well in cold
100
Listeria monocytogenes primarily infects:
```
Pregnant women (fetus/newborn)
Immunocomprimised adults
```
101
Rickettsia rickettsiae is responsible for what disease?
Rocky mountain spotted fever
102
True or False: Rickettsia Rickettsiae are short rods, and (difficult to stain) gram (-).
True.
103
What is the life cycle of Chlamydia trachomatis?
Elementary bodies attach to cell, are endocytosed, survive and become reticulate bodies
Reticulate bodies replicate, metabolize, pack into elementary bodies, and escape host cell
104
Which chlamydial being is the only one that divides?
Reticulate bodies
105
Which chlamydial being it the only one that's infectious?
Elementary bodies
106
Elementary bodies house what kind of virulence factor that prevents it from fusing with a lysosome?
T3SS, it alters the endosome
107
What is the most common STI?
Chlamydia
108
What is the tx for chlamydia?
Doxycycline or azithromycin
| If pregnant, use erythromycin and amoxicillin
109
Actin-based cell-cell spread in intracellular bacteria accomplishes what?
Evade immune system by not going through the blood stream.
110
Reactive arthritis can follow what bacterial infection?
Chlamydia
