Unit 1 Deck 2 Flashcards
1
Q
Name the hydrophobic part of sphingomyelin.
A
- Sphingosine hydrocarbon chain
2. Fatty acid chain
2
Q
Name the hydrophilic part of sphingomyelin.
A
- Phosphate
- Choline
(phosphoryl chloline)
3
Q
Name the hydrophobic part of the phosphoglycerides
A
- Fatty acid chains
4
Q
Name the hydrophilic part of the phosphoglycerides.
A
- Phosphorylated OH group
5
Q
Name the hydrophobic part of cholesterol
A
Everything but the OH!
6
Q
Name the hydrophilic part of cholesterol
A
OH group
7
Q
True or False: An interstitial deletion is more likely to be deleterious than a terminal deletion.
A
False. The deletion does not depend on the area, but the size, and which chromosome is involved.
8
Q
After five miscarriages, karyotype analysis revealed that your patient, Sara, has a paracentric inversion of chromosome 8. She wants to understand what this means. What is her reproductive capability?
A
Biologically, it is quite possible for Sara to have normal children, but she needs to be patient because the presence of the inversion may result in further miscarriages. For this type of inversion, chromosome imbalances are usually lost during gametogenesis, so the highest probability is that children will have a balanced genome and will be clinically normal with respect to the inversion. If the partner also has a chromosomal abnormality, that will complicate the issue further.
9
Q
A baby is born with multiple congenital anomalies. By age 3, he clearly shows signs of developmental delay. Phenotypically, he appears very different than his siblings and parents. A family history shows three generations of multiple miscarriages in the father’s family. A paternal great-uncle was delayed and died early in life. What is the most likely cause of this child’s medical problems?
A
This is a chromosomal abnormality. the scenario described above is classic for a familial chromosome abnormality. The three generations of multiple miscarriages clinches the interpretation.
10
Q
Name the syndrome associated with the aneuploidy 47,XXY
A
Klinefelter’s syndrome
11
Q
Of the 4 main sex chromosome aneuploidies 47,XXY, XYY, 45,X and XXX, which must be only a parternal meiotic nondisjunction error?
A
XYY, paternal meiotic II nondisjunction
12
Q
Name three characteristics of a XXX female
A
- Average to tall in stature
- Usually doe to maternal meiosis I error
- Learning deficit or fertility problems possible
13
Q
Name 3 characteristics of Klinefelter’s syndrome
A
- May have breasts, or small testes
- Tall
- Infertile
- May have learning disabilities
- 50% are due to a paternal meiosis I error
14
Q
In what syndrome might a patient seek surgical correction of a webbed neck?
A
Turner syndrome
15
Q
Turner syndrome may be from a deletion of the X (45,X), however give me some other examples in which it might occur:
A
Mosaicism, 45,X/46,XX with rearrangements, 45X/46,XY
16
Q
In Turner syndrome, the X is usually maternal. What does this mean for the source of the nondisjunction?
A
Paternal meiotic nondisjunction the most common source of the error.
17
Q
What is a health risk for Turner syndrome patients with a complete or partial Y chromosome in at least one cell line?
A
Increased risk for gonadoblastoma
18
Q
What phenotype will an individual with 45,X/46XY have?
A
Depends! This depends on what cells are most active at the time of development.
19
Q
What is another term for “androgen insensitivity?”
A
“Testicular ferminization”
20
Q
How can you have an XY female?
A
Y chromosome is fully present and functional, but ther is a mutation in the androgen receptor gene located on the long arm of the X chromosome, resulting in no production of androgen receptor.
21
Q
What is the non-cytogenetic source of an XX male?
A
Congenital adrenal hyperplasia (CAH), in either the mother (ambiguous genitalia) or the fetus –> results in in-utero virulization of the fetus
22
Q
What is the defect in congenital adrenal hyperplasia?
A
Biochemical imbalance, lack of enzyme 21-hydroxylase. Without this enzyme, the normal biosynthetic pathway is blocked and androgens accumulate in the body
23
Q
What is the cytogenetic source of an XX male?
A
XY recombination in the pseudoautosomal region on the short arms of the X and Y chromosomes.
24
Q
What is the effect of a balanced translocation?
A
No clinical abnormalities. The issue becomes the offspring of this individual (ie if SRY gene was translocated to an X chromosome, and that X is passed on)
25
How can an individual have a balanced translocation with clinical abnormalities?
If the break occurred in a gene, resulting in loss of that gene or function
26
Unbalanced chromosomal complements are most commonly associated with what clinical feature?
Developmental delay or mental retardation
27
Give an example of a syndrome associated with a terminal deletion.
Wolff-Hirschorn syndrome, loss of end of chromosome #4, aka "4p syndrome"
28
What is a recriprocal translocation?
A "balanced" translocation of genes on nonhomologous chromosomes
29
Eukaryotic cilia ans flagella are powered by the motor protein dyenin. What are their cargoes?
Doublet microtubules
30
What is the function of taxol?
Taxol is a chemotherapy agent that destabilizes dynamic microtubule structures in dividing cells.
31
Microvilli are protrusions of the plasma membrane whose shape is maintained by _____.
Microfilaments
32
True or False: The neurofilament class of intermediate filaments provides tracks for retrograde transport of neurotropic viruses.
False
33
The normal distribution of endoplasmic reticulum and Golgi membrane systems in a typical mammalian cell is dependent upon ___________.
Microtubules and microtubule-associated motor proteins
34
Which kind of DNA contains more repetitive sequences?
Heterochromatin
35
What are DNA single-stranded binding proteins used for?
Proofreading or maintenance
36
Name the four types of DNA damage.
1. depurination or modification of DNA bases by radiation, chemical agents etc
2. two-base alterations (thymine-thymine dimers with UV light)
3. strand breaks from radiation or free radicals
4. cross-linkage of DNA with its associated proteins from chemical agents
37
p53 plays a key role as what during the cell cycle?
p53 is a tumor suppressor gene, active at G1 and G2 checkpoints, mutated in Li-Fraumeni tumor syndrome
38
What condition is caused by copying errors that cannot be fixed by mismatch repair?
Hereditary nonpolyposis colon cancer, HNPCC
39
What is a potential effect of germ-line mosaicism?
Neither parent is affected by a disease, but all their children may be affected.
40
What kinds of cells must be used to perform karyotype analysis?
A karyotype can be obtained from dividing cells (blood leukocytes), bone marrow, fibroblasts, amniocytes), but NOT from frozen or formalin-fixed cells. *requires metaphase for chromosomal view.
41
What does an individual with cytogenic notation 46,XX,del(5p) mean?
Female with a deletion the short arm of chromosome 5
42
Why might one use FISH (fluorescent in situ hybridization) in cytogenetics?
FISH can detect microdeletions in chromosomes that might encompass several genes
43
Define the term "mosaicism."
Mosaicism is 2 or more cell lines with different karyotypes in the same individual. For example, a person who is 45,X/46,XX is a Turner syndrome mosaic.
44
What is chimerism?
Extremely rare, when 2 different cell lines from two different zygotes arise in the same individual
45
What is polyploidy?
Entire extra sets of haploid chromosomes, ie 69,XXX triploidy. This will end in a spontaneous abortion or severely malformed, short-life infant
46
What is euploidy?
Normal chromosome number and composition
47
Paternal meiotic nondisjunction in meiosis I would cause what syndrome?
47,XXY, Klinefelter's syndrome (24,XY gamete)
48
Actin is a globular protein that assembles to form ______
Microfilaments.
49
Actin filaments are almost exclusively associated with what part of the cell?
The plasma membrane
50
What two cofactors are needed for actin assembly?
ATP and Mg2+
51
Actin binding proteins are responsible for what functions? Name 6.
1. generate force (myosin)
2. crosslink
3. regulate motility (troponin)
4. bundle (alpha-actinin)
5. cap (capping proteins)
6. anchor, as to the plasma membrane
52
The combination of the plasma membrane and an underlying mesh of crosslinked actin filaments is called the ________.
Cell cortex
53
Which kind of actin-associated membrane structures are branched/unparallel and involved in a migrating cell?
Lamellapodia
54
Name the four main actin-associated membrane structures.
1. Microvilli - GI
2. Lamellapodia - migrating cell
3. Contractile ring - anaphase/telophase cell
4. Stress fibers
55
Name the three small G-proteins that regulate actin assembly patterns.
1. Rho
2. Rac
3. Cdc42
56
What is the function of ARP, the actin-related protein?
ARP mediated the assembly of a BRANCHED array of actin filaments at the leading edge of an extending cell membrane. ie fibroblasts
57
How are actin monomers made available in treadmilling?
They disassemble from the (-) or slow-growing end of the actin, and can then be added to the (+) or fast-growing end.
58
What are two actin-assembly poisons?
Phalloidin (death cap mushroom)
| Cytochalasin (in mold)
59
How can myosins form dimers (two-headed)?
Coiled coil interactions of the C-terminal tails
60
True or False: Myosin I forms filaments.
False. Myosin I is a monomeric myosin, and binds to membranes or actin (toward plus end). Important in non-muscle cells.
61
How does myosin II assemble?
Into bipolar filaments, with the heads facing in opposite directions. Basis of the thick filaments in muscle contraction.
62
How does myosin II work with actin in a migrating cell?
Pulls up the rear of the cell
63
What are the 3 steps in myosin-based of thick filament-based regulation?
1. Ca2+ causes phosphorylation of MLCK
2. MLCK phosphorylates myosin "neck" (light chain)
3. spontaneous self-assembly of myosin tails
64
What is a myofibril?
A muscle cell - long, multi-nucleate, made up of repeating units called *sarcomeres*
65
What is a sarcomere made up of?
Anchored bundles of interdigitating actin and myosin filaments
66
Where are the plus ends of actin filaments anchored in a sarcomere?
Z disc
67
How is a sarcomere anchored to the sarcolemma?
Dystrophin. Together with actin, they strengthen muscle cell membranes
68
Name the steps in muscle contraction
1. ATP binds myosin, changes its conformation
2. Myosin releases from actin filament
3. ATP hydrolyzed to ADP
4. Energy created causes a small translocation of the myosin head
5. Dissociation of Pi allows myosin to reassociate with the actin filament (power stroke)
69
What happens in actin or thin filament-based regulation?
1. Ca2+ binds to troponin C
2. Conformational change of troponin C induces movement of troponin I and troponin T
3. Troponin T moves tropomyosin away from myosin-binding site on actin
70
What are the three functional characteristics of myosin heads
1. ATP binding and hydrolysis site
2. Actin binding site
3. Lever arm
71
What is the difference between the rigor and relaxed states of muscles?
In rigor, no ATP, so myosin head is bound to actin. In relaxed, myosin head is bound to ATP, and will stay relaxed until Ca2+ is released.
72
What happens to Ca2+ when a muscle is relaxed?
Following a contraction, it is being pumped back into the sarcoplasmic reticulum by a Ca-ATPase.
73
Why does myosin-II, but not myosin-I form bipolar thick filaments?
Myosin-I does not have a tail domain that engage in coiled coiling. Its tail binds to membranes, in general
74
For what diagnoses would you consider use of an N95 mask?
TB, chickenpox, shingles, measles, pandemic influenza
75
What is the difference between disinfection and sterilization?
Sterilization refers to the destruction of all microbial life and is carried out in health care facilities by physical or chemical methods.
Disinfection refers to a process that eliminates many or all pathogenic microorganisms *except* bacterial spores, on inanimate objects.
76
What is antisepsis?
Antisepsis is the reduction of microorganisms on living tissue/skin. This process does not kill spores and its products cannot be used as disinfectants. It can kill germs in/on the body and on inanimate objects *related to medical/surgical use*
77
How are single-use medical supplies ensured for sterility?
Gamma radiation
78
True or False: Alcohol-based rubs kill bacteria and most viruses.
True, for intermediate and low level of disinfection
79
At high concentration, what product would be effective at killing HIV and hepatitis viruses?
Chlorine/chlorine-releasing compounds.
80
What shower might be prescribed to a person about to undergo a major surgery?
Chlorhexidine (2% soln)
| pHisoHex - hexachlorophene detergent cleanser
81
What is a "quat"?
Quats are quaternary ammonium compounds ie benzalkonium chloride, used as antimicrobials and disinfectants. Lethal agains TB and non-enveloped viruses.
82
What can kill both gram-positive and gram-negative bacteria within two hours of exposure, and delivers continuous and ongoing antibacterial action, even after repeated contamination?
Copper
83
A patient is diagnosed with methicillin resistant Staphylococcus aureus pneumonia. What type of isolation is MOST appropriate for this client?
Contact isolation - anything to prevent direct or indirect contact. Gown is required when entering the room, patient equipment is not shared.
84
The most widely used, effective, economical and reliable method of sterilization used in the health care setting is:
Moist Heat.
85
What makes droplet precautions more extensive than contact precautions?
The patient must wear a mask if he exits the room
The health care providers must wear masks when the enter the room
The room must be private.
86
What four types of infections are responsible for over 75% of HAI's?
Catheters
Surgical site infections (SSI's)
Bloodborne infections
Pneumonias
87
When might you use paracetic acid to disinfect?
For organisms that like water systems, ie legionella. Also used in gas phase/plasma sterilization
H2O2 plus acetic acids
88
What kind of process would you use to disinfect endoscopes and related material?
Plasma sterilization. Safe, non-toxic, dry, low-temp sterilization in about 1 hour.
89
What is the "organism" with the greatest resistance to disinfectants?
Prions, then coccidia, then spores, then mycobacteria
90
What process renders beef tartar safe to eat, and eliminates the risk of residual E. Coli on meat?
Irradiation in the form of ionizing radiation. Medical application: Irradiated RBC's prevent graft vs. host disease (GVHD)
91
What is the only liquid chemical that can be considered a sterilant?
Cidex - an aldehyde solution
92
What substance is being used in many personal care products that has not been shown to provide any extra benefit beyond anti-gingivitis effects in toothpaste?
Triclosan
93
What is a bacteria that is considered a normal flora commensal on our skin?
```
Staph epidermidis (can also be staph aureus, but will cause disease if not contained)
Candida albicans
```
94
What is a bacteria that is considered a normal flora commensal in our throat?
Staph, strep, neisseria (Neisseria can cause meningitis in the bloodstream of an unvaccinated person)
95
What is a bacteria that is considered a normal flora commensal in our gut?
Coliforms - bacilli, gram (-), non-sporulating
96
An opportunistic pathogen that has violated the terms of commensal existence would have what kind of ID50, and what kind of LD50?
High LD50, Mid to low ID50. (LD = lethal dose)
97
What are three ways that exotoxins--polypeptides secreted from the pathogen or injected by T3SS pilus--have or cause pathogenicity?
1. interfering with actin polymerization
2. interfering with signal transduction
3. Superantigenicity
98
Several important exotoxins have an A-B subunit structure. What does this mean?
A has the toxic activity, and B delivers A to the target site.
99
True or False: Previous exposure to an endotoxin is protective due to immune recognition.
False. Neither previous exposure nor vaccine is protective.
100
What are Koch's postulates?
1. Observe disease
2. Culture pathogen
3. Infect new host from culture
4. Observe same disease
5. Culture same pathogen
* *Anything less is suppositional**
101
What is the concept of colonization resistance?
Normal flora--commensal bacteria and yeasts have taken up all the good spots in an organism, thereby protecting the organism from infection from a true pathogen.
102
20% BY MASS of stools is made of:
Bacteria!
103
What bacteria helps women maintain low pH in the vagina?
Lactobaccili, candida overgrowth follows too high a pH.
104
15-20% of women carry what bacterium that can cause meningitis in newborns if no prophylactic treatment was sought?
Strep B.
105
The presence of what bacteria predisposes women to toxic shock syndrome?
Staph aureus.
106
What is a noncommunicable infection?
You get the pathogen from the environment, not a previous host, ie botulism, Legionnaire's Disease
107
What is the difference between an epidemic and a pandemic?
Epidemic - much more frequent infection than usual
| Pandemic - worldwide distribution of infection.
108
ALL virsus and some bacteria are _________
Obligate intracellular parasites. They must enter the host's cells to reproduce.
109
What are siderophores?
Siderophores are small, high-affinity iron chelating compounds secreted by microorganisms such as bacteria, fungi and grasses.
110
What are three modes of vertical transmission?
1. Transplacental
2. Vaginal delivery
3. Breast milk
111
What is fomite transmission?
ie. Washcloth or countertop
112
In a patient, what effect does S. aureus's coagulase quality have?
It breaks down fibrinogen to form a fibrin clot.
113
What does pyogenic mean?
Pus-forming (neutrophil reaction)
114
What is a granulomatous inflammatory response?
Macrophages kill most of the bacteria, but some survive inside macrophages within a granuloma.
115
Name 3 facultative intracellular biggies.
1. Listeria
2. Legionella
3. Mycobacteria
116
Name 2 obligate intracellular biggies.
1. Chlamydia
| 2. Rickettsia
117
Exotoxins are made and secreted by ___1____ AND gram (-) bacteria, they are made of ____2___, are known to be some of the most ___3____ substances known, often encoded on ____4____ or brought in by a ____5____. Exposure ___6____ induce neutralizing antibodies, thus you can raise a ___7___ against inactivated ___8___ for many toxins.
1. gram (+)
2. polypeptides
3. toxic
4. plasmids
5. bacteriophage
6. DOES
7. vaccine
8. Toxoid
118
What is another term for T3SS (type 3 secretion system)?
Injectosome
119
What is the prodome period in the timeline of an infectious disease?
Nonspecific symptoms - fever, malaise, right after incubation period
120
A man asymptomatically carrying dermal S. aureus gets a bad infection when he burns his hand. Which assumption of the commensal relationship was violated?
Containment in the proper compartment
121
Pseudomembranous colitis is often caused by what pathogen?
Chlostridium difficile
122
What is the difference between type 3 and type 4 secretion systems?
Type 4 secretion systems can ALSO transmit DNA, in addition to proteins.
123
What is legionella's strategy for host cell takeover?
Legionella is taken up by macrophages and gets contained in an altered phagosome, then becomes motile and escapes the phagosome, then lyses the cell to spread to another
124
What does LD50 mean?
A dose that was lethal to 50% of the experimental population.
125
A bacterium that has a very low pathogenicity and a high ID50 is most likely a
Nonpathogen.
126
What is a superantigenicity toxin?
This kind of exotoxin causes activation of 3/4 less T cells than would normally respond to an infection, can cause shock (TSS), and multiple organ failure, ie staph aureus, strep pyogenes
127
True or False: Candida albicans is part of the normal flora of both women and men.
True
128
The main host defense against bacterial exotoxins is:
IgG and IgM antibodies.
129
What toxin causes paralysis by blocking release of acetylcholine?
Botulism toxin
130
What toxin inhibits protein synthesis by blocking elongation factor-2?
Diptheria toxin
131
What toxin stimulates T-cells to produce cytokines?
TSS-toxin
132
What toxin stimulates production of cAMP by adding an ADP-ribose to a G protein?
Cholera toxin
133
What toxin inhibits the release of inhibitory neurotransmitters causing muscle spasms?
Tetanus toxin
134
What enzyme phosphorylates? What enzyme dephosphorylates?
Kinase phosphorylated, Phosphatase dephosphorylates
135
What residues are most commonly phosphorylated?
The -OH groups of serine, threonine, tyrosine
136
To what GPCR subunit does GTP always bind?
Alpha subunit
137
True or False: G-proteins covalently bind GTP to induce an off state
False and false. G-proteins *non-covalently* bind GTP to induce a signal-on state
138
What is a GEF?
A GTP-exchange factor, which aids in the release of GDP and the binding of GTP.
139
How are trimeric G proteins linked to the plasma membrane?
Lipid tails
140
What are the steps in GPCR activation?
1. Ligand binds receptor (7-pass transmembrane receptor) on extracellular side of cell.
2. Inner doman of receptor changes conformation, increasing affinity for GCPR.
3. Alpha subunit binds receptor and GDP is exchanged for GTP
4. GTP binding to alpha subunit changes conformation of alpha subunit to reduce affinity of alpha for beta/gamma subunits and they separate.
5. **Both alpha and beta/gamma subunits are now activated.
141
What might be an effect of an activated beta/gamma dimer?
Opening of an ion channel
142
How quickly is GTP hydrolyzed to GDP on an alpha subunit of a trimeric G-protein?
Slowly! The inorganic phosphate comes off quickly, but GDP is slow to remove itself from the alpha chain.
143
What is the cascade following activation of a Gs alpha subunit?
1. Gs-alpha binds to adenylate cyclase
2. AC catalyzes the conversion of ATP to cAMP many times over
3. cAMP binds to PKA and activates it
4. PKA has both gene regulatory effects and specific target proteins which it phosphorylates
144
What is the structure of PKA?
PKA has 2 regulatory subunits and 2 catalytic subunits. When cAMP binds to the regulatory subunits, the two catalytic units dissociate and are activated.
145
Destruction of cAMP by ________ leads to reassociation of regulatory and catalytic subunits, inhibiting PKA.
Phosphodiesterase
146
Do intermediate filaments have polarity? How does this impact their ability to be motility tracks?
IF's have NO structural polarity (unlike actin filaments). They are NOT useful as motility tracks because motor proteins wouldn't know which way to move on them.
147
Name the 4 types of IF's.
1. Nuclear lamins
2. Vimentin-family
3. Keratins
4. Neurofilament proteins.
148
What are IF's known for?
Tensile strength
149
Where are vimentin and vimentin-related IF's found?
1. Connective tissue
2. Muscle cells
3. Glial cells
(all mesodermal derivations)
150
Where are keratin IF's located?
Epithelial cells, skin, hair, nails
151
Where are neurofilament IF's located?
In both the CNS and PNS
152
What are the two types of IF's found in the nervous system?
1. Neurofilaments
| 2. Vimentin-family
153
How do IF's, like keratins, seem to "connect" from once cell to the next?
IF's connect at plasma membranes to desmosome junctions (made of desmin). Gives tissue wide structural support.
154
Lamin A mutations are related to what disease?
Progeria
155
In cancer diagnosis and treatment typing of what cytoskeletal element can help identify the source of the cancer?
IF's being made.
156
Actin motors are made of ____1____ whereas microtubules motors are made of ___2___ and ___3___.
1. Myosin
2. Dyenin
3. Kinesin
157
What cofactors are required for microtubule assembly?
Mg2+, GTP
158
What are two anti-cancer drugs that work to stop microtubule assembly?
1. Taxol
| 2. Vinblastine/vincristine
159
What is a centrosome made up of?
1. 2 centrioles perpendicularly aligned (triplet MT's)
2. centrosome matrix surrounding the centrioles, creating a ball
3. Gamma-MT ring complexes, forming the sites for MT growing (bunch of plus-ends sticking out)
160
Dyneins move toward the __1__ end of MT's, while kinesins move toward the __2__ end.
DYN-MIN(us) end
| Kinesin - plus end
161
What are the 9+2 organelles? Why are they called that?
Cilia and flagella, so named because of the association of the building blocks of 9 doublet MT's on the edge, with 2 central MT's.
162
What is the mechanism of colchicine?
Used for gout, works by binding to free tubulin and preventing its assembly into MT's.
163
MT's that no longer show dynamic instability have undergone _______.
Maturation - post-translational modification of alpha and beta tubulin by acetylation and detyrosination contributes to the stability of mature MT's.
164
Give two examples of mature MT's.
1. Nerve axons
| 2. Cilia
165
Name two MAPS's.
1. MAP2 - found in dendrites and cell bodies of nerve cells
| 2. Tau - found in axons associated with long arrays of MTs.
166
Dynein and kinesin motor proteins are central to the most basic functions of microtubules: ____1____ and ____2____.
1. Organelle and vesicle transport
| 2. Segregation of chromosomes at mitosis
167
The Golgi uses ____1____ to gather MT ___2___ ends.
1. Dynein
| 2. Minus
168
The ER uses ___1___ to ___2___ between its attachment sites on the nucleus, and MT ___3___ ends toward the periphery of the cell.
1. Kinesin
2. stretch
3. plus
169
What is an axoneme?
Doublet MT's and all their associated proteins form a structure called an axoneme.
170
The flagellum or cilium consists of the ___1___ and is surrounded by specialized cell membrane, which forms a separate cellular compartment closed at the base through attachments to the ___2___, which is formed from ___3___.
1. Axoneme
2. Basal body
3. Triplet MT's
171
What are the functions of dynein and kinesin in cilia?
Cargo transport
"IFT" - intraflagellar transport
**Not for beating**
172
Kartegener's Syndrome is caused by:
AKA PCD - primary ciliary diskinesia
Malfunction/lack of motility in cilia that should be beating/motile, leading to:
1. respiratory disease
2. situs inversus
3. Heterotaxy (this has bad heart defects associated with it)
173
Non-motile cilia lacking ___1___ are also called ___2___.
1. Dynein arms
| 2. Primary cilia (not to be confused with Kartagener's syndrome, aka primary ciliary disease, PCD)
174
PKD, Polycystic Kidney Disease, is caused by:
Mutations in the genes that encode protein needed for assembly of primary/non-motile cilia, normally present in the cells lining the kidney tubules.
175
Besides PKD, name a condition associated with disruption to sensory cilia.
Barter-Biedl Syndrome
| --obesity, retinal degeration, retardation, diabetes, PKD etc.
176
What produces the movement of cilia and flagella?
MT-sliding - Dynein ATPase activity is coupled to MT-sliding
177
What structures give IF's their individuality?
Globular domains at the end of their coiled-coil dimers.
178
What makes up the heterodimer tubulin unit?
Alpha tubulin and beta tubulin
179
What kind of motor protein carries the heaviest cargo in the cell?
Dynein - can even carry the nucleus!
180
What pathology occurs when the migration of neurons to their proper places in the brain is inhibited during development?
Lissencephaly
181
What is the function of a primary cilium?
Receptor, as in renal cells, rod and cone cells etc. Non-motile
182
Which cytoskeletal element is most often important for changes in cell shape?
Microfilaments (requires a link to the cell membrane)
183
What is the cargo carried by a dynein motor in a cilium?
Cytoplasmic dyneins typically move vesicles, but in cilia, each of the doublet MT's acts as both track and cargo.
184
Why is ciliary assembly important for vision?
Vision requires display of the light receptor, rhodopsin, in sensory cilia in rod and cone cells.
185
True or False: cAMP binds directly to transcription factors in a second-messenger cascade.
False. cAMP binds to PKA which activates TF's.
186
What is an unusual function of a Gi protein?
Can alter K+ channel conductance in some cells. This is unusual because G proteins usually initiate a secondary cascade.
187
Name the steps in a Gq cascade.
1. Signal molecule binds to GPCR
2. GPCR changes affinity of alpha subunit for GTP, and GDP is replaced by GTP on alpha subunit
3. Activated alpha subunit removes itself from the b/g subunits and attaches to a phopholipase C (PLC), also in the membrane
4. PLC changes conformation, and this action hydrolyzes the GTP to GDP in the alpha subunit, which detaches from the PLC.
5. PLC cleaves PIP2 (phosphoinositol bisphosphate)
6. PIP 2 becomes diacyl glycerol (DAG) and inositol triphosphate (IP3).
7. IP3 diffuses into the cytoplasm and opens Ca2+ gates on the ER
8. Ca2+ does 2 things, first, it joins DAG back up at the plasma membrane, and together they activate PKC, and second, it binds to calmodulin to activate it
9. Calmodulin then activates serine/threonine-specific CAM kinases, ie MLCK
188
What is a phorbol ester?
An irreversible binder to (and activator of) PKC. It is classified as a tumor promoter
189
What molecule participates in transphosphorylation?
Tyrosine kinase receptor (dimerization and transphosphrylation)
190
What is a major family of monomeric G-proteins involved in second messenger systems?
ras family
191
What is a major family of monomeric G-proteins involved in vesicle trafficking?
rab family
192
Once activated by receptor tyrosine kinase activity, ras does what?
Stimulates a MAP (mitogen activated protein) kinase cascade (also works with C-kinase to achieve this)
193
MAP-kinases are mostly ___1___ kinases with specificity for targets important in ___2___.
1. serine/threonine
| 2. growth control
194
What is the difference between receptor tyrosine kinases and tyrosine kinase-linked receptors?
TKLR's have associated proteins that are phosphorylated, but they themselves are only phosphorylated once (not three times), and the phsophorylation attracts the regulatory gene proteins which associate, then become activated, then disassociate to migrate to the nucleus
Example of this: JAK-STAT pathway, **where JAK kinase (attached to TKLR) transphosphorylates itself.
195
What are SH2 domains, and what role do they play in signal transduction?
SH2 domains bind to amino acid sequences that include phosphorylated tyrosine residues. By binding, they change the conformation of the SH2 domain protein, and signal to the rest of the cell that the receptor tyrosine kinase has been activated.
196
Compare the regulation of GTPase activity for monomeric G proteins and trimeric G proteins. Which type usually has the higher rate of spontaneous GTPase activity?
In general, trimeric G-proteins hydrolyze GTP on their own, but monomeric G proteins normally require a GAP to hydrolyze their GTP.
197
True or False: In G-protein signaling pathways, no signal diffuses throughout the cell.
False: Ca2+ and cAMP do this.
198
How is A-kinase activated?
PKA is activated by cAMP.
199
How is PKC activated?
C-kinase is activated by DAG (remember both are associated with the plasma membrane)
200
How is CAM kinase activated?
Ca2+, usually through Gq pathway
201
Why do anaerobic bacteria hide from blood?
1. To avoid O2
| 2. To avoid immune surveillance
202
Why should you never feed a baby honey?
The honey may have chlostridium spores that the immunosuppressed cannot clear, ie babies. (Botulism)
203
What bacteria causes gas gangrene?
Chlostridium perfringens, **known for necrosis of the bowel**
204
What does gas chromatography tell you about a bacterial sample?
Gas chromatography tells you what organic acids and alcohols are being produces by a certain bacterium, and serves as a footprint.
205
Why do anaerobic bacteria growl slowly?
Because if they are only using fermentation, their metabolic system is comparatively inefficient.
206
What is the tx for anaerobic infections?
Debride wound, or drain abscess
Use antitoxin if applicable (tetanus, botulism)
Antibiotics
207
What three bacterial species use soil as a reservoir, and produce spores, and need those spores to survive the transfer from soil to human?
1. C. perfringens
2. C. botulinim
3. C. tetani
208
What bacteria is responsible for a jaw-nodule infection?
Actinomyces, creates an abscess
209
What does GNAB stand for? What does it include?
Gram Negative Anaerobic Bacilli - primarily bacteroides and prevotella, also includes the less common fusobacter
210
What is the primary virulence factor for C. tetani?
Tetanus toxin, tetanospasmin
211
What is the primary virulence factor for C. botulinim?
Botulinim toxin
212
What is the primary virulence factor for C. perfringens?
Tissue-degrading enzymes for gas gangrene.
| Enterotoxin for food poisoning
213
What is the primary virulence factor for GNAB?
Capsule, some tissue-degrading enzymes
214
What condition does C. difficile cause?
Pseudomembranous colitis
215
What is the primary virulence factor for C. difficile?
Exotoxins A and B.
216
What condition can infection with GNAB cause?
Abscesses
217
How can you get foodborne botulism if the botulinim bacteria cannot survive in the gut?
There is already exotoxin in the food you have eaten.
218
What is the new technology replacing gas chromatography in bacterial identification?
Benchtop shotgun sequencing, become less expensive
219
Clostridium, botulism, Prevotella and Actinomyces are what shape of bacteria?
Rod, **actinomyces, as the name implies, is a long, filamentous rod
220
What anaerobes are part of normal flora, when not causing disease?
C. Difficile, Actinomyces, GNAB
221
What is the target of the A-B subunit exotoxin of C. tetani?
Motor neuron, gets into cell, retrograde neuronal transport, results in loss of central inhibitory (GABA) activity on motor and autonomic neurons
222
Of what recurring themes in exotoxin function does tetanospasmin remind you?
1. Interferes with signal transduction
| 2. AB subunit structure
223
What is the tetanus vaccine called?
DTap
224
What is unique about C. Diff?
Even though it is part of our normal flora (3% in overall population, 30% in hospitalized population), it is spore-forming
225
What is the mode of transmission of C. diff?
Fecal-oral
226
What antibiotics are recommended for C. diff infection?
Oral metronidazole
| Vancomycin
227
What are the bacterial enzymes required to grow in an oxygen-rich medium?
1. catalase
2. peroxidase
3. superoxide dismutase
228
True or False: The clostridia bacterial group are gram (-).
False. The clostridia (and actinomyces) are gram (+) bacteria.
229
Colonoscopes cannot be autoclaved, therefore they can potentially transmit what from one patient to the next?
C. diff!!!!
230
True or False: Integrins are only found in junctions linking the extracellular matrix to the actin cytoskeleton.
False
231
If a protein being translated lacks a sorting signal, where will it end up?
It will stay in the cytosol.
232
What are the three mechanisms of protein transport in the cell?
1. Nuclear pores
2. Protein translocators
3. Vesicles
233
True or False: All proteins destined for organelles are imported cotranslationally.
False. Proteins destined for the ER are imported cotranslationally, but for mitochondria and peroxisomes, they are imported posttranslationally.
234
What is the general size of a signal sequence destining a protein to a particular organelle?
Anywhere between 3-60 aa's.
235
When would a signal peptidase cleave a signal sequence in a nascent protein?
If the sequence was at the N-terminus, after being transported.
236
What can be found in the mitochondrial matrix? Name 2 things.
1. Mitochondrial genome, and its transcriptional and translational machinery
2. high concentration of enzymes a) that break down fatty acids **via B-oxidation** an b) involved in the citric acid cycle
237
Where can proteins of the electron transport chain and ATP synthase be found?
On the inner membrane of the mitochondria -- needed to help maintain electrochemical gradient
238
What kind of molecules can travel through outer mitochondrial membrane porins?
Small, about <5000 daltons (these porins are aqueous channels)
239
Where can cytochrome c be found?
The intermembrane space of the mitochondria.
240
What is cytochrome c?
It is a component of the ETC. It is released into the cytosol during apoptosis.
241
Where does glycolysis happen in a cell?
Glycolysis, the breakdown of glucose to pyruvate, happens in the cytosol.
242
What is the caspase cascade?
The caspase cascade is an intracellular proteolytic cascade responsible for cleaving key intracellular proteins, inducing apoptosis. It is started when the mitochondria is stimulated to release cytochrome c into the cytosol.
243
What do TOM and TIM stand for?
TOM - transporter outer membrane
TIM - transporter inner membrane
Both form complexes in the mitochondria for protein transport.
244
Chaperones are known to exist in the ER lumen to aid in protein folding. Where else in the cell can they be found?
Chaperones can also be found in the mitochondrial matrix, as protein import must be completed with the protein in an unfolded state.
245
Name the steps in protein import into the mitochondria.
1. Precursor protein binds to a receptor associated with a TOM complex.
2. The TOM complex diffuses laterally to find a TIM complex.
3. When a TIM complex is found, the protein is transferred, signal sequence first, through the TOM and TIM, into the matrix.
4. Chaperones help the protein fold.
5. Signal peptidase cleaves the signal peptide, and the protein completes folding.
246
What are the energy requirements for protein translocation into the mitochondrial matrix?
1. ATP hydrolysis
| 2. Electrochemical gradient
247
What are the relative sizes of the human genome and the mitochondrial genome?
1. The mito genome is about 16,500 bp
| 2. The human genome is about 3 billion bp
248
True or False: Mitochondrial DNA is transcribed the same way that regular human DNA is.
False!! The Mito genome, apart from being circular, has no introns.
249
What kinds of RNA does the mitchondrial genome code for?
1. 2 rRNA
2. 22 tRNA
3. 13 mRNA
250
FUN FACT!!
Each mitochondrion contains 10-20 copies of the mitochondrial genome which are found in clusters in the mitochondrial matrix.
251
True or False: Mitochondrial replication is not limited to the S phase, and occurs throughout the cell cycle.
True!! As a result, the total # of mitochondrial DN molecules doubles in every ell cycle as the organelles grow and divide prior to each cell division.
252
The 13 mRNAs encoded by the mitochondrial genome become
They all become subunits in complexes involved in electron transport and ox phos.
253
In addition to breaking down alcohols, fatty acids and toxins, peroxisomes are known to produce what?
Peroxisomes synthesize special phospholipids like cholesterol, bile acids and some other lipids.
254
How many peroxisomes are in a typical human cell?
Hundreds!
255
What is beta oxidation?
The breakdown of fatty acids.
256
Why do many peroxisomal disorders lead to neurologic disease?
Because peroxisomes are responsible for catalyzing the initial steps of creating plasmalogens. Plasmalogens are the building blocks of the myelin sheath. If there is a defect in plasmalogen creation, serious abnormalities in the myelination of nerve cells can occur.
257
In what two organelles does B-oxidation occur?
1. Mitochondria
| 2. Peroxisomes
258
Peroxisomes contain enzymes that remove H atoms from organic substrates in an ___1___ reaction that produces ___2___.
1. oxidative
| 2. H2O2
259
What is H2O2 used for in peroxisomes?
Catalase uses H2O2 to oxidize a variety of substrates, is phenols, formaldehydes, formic acid and alcohol. **Important in kidney and liver cells**
******25% of consumed alcohol is oxidized to acetaldehyde by catalase.
260
What are the two functions of catalase w/r/t H2O2?
1. Oxidation of toxic substrates
| 2. Converts it to water when H2O2 is not needed.
261
___1___ ---> B-oxidation ---> ___2___
1. Long chain fatty acids
| 2. Acetyl CoA (blocks of 2-C's, much shorter than original chain)
262
Name a disorder associated with peroxisome biogenesis.
Zellweger syndrome, "empty peroxisomes" due to defect in protein import, patients die soon after birth
263
Name a disorder associated with deficiency of a single peroxisomal enzyme.
X-linked Adrenoleukodystrophy (ALD), results in partially functional peroxisomes, lack a membrane protein to degrade fatty acids which leads to their build-up...their build-up leads to demyelination of neurons and adrenal insufficiency
264
What is the old treatment for ALD?
Allogeneic hematopoietic stem cell transplantation (HCT) - has high morbidity, donor not easy to find always, must be performed before brain lesions are bad.
265
What is the new/upcoming treatment for ALD?
Gene therapy. Recent success suggests this is a new tx. Used HIV-derived vector to fix the children's stem cells in vivo, chemotherapy was used to irradiate the bone marrow, which was then replaced with new, WT cells.
266
The first successful clinical test of HIV-derived vector in HSC-based gene therapy was to treat what disorder?
X-linked ALD.
267
True or False: Once inside the ER or embedded in the ER membrane, individual proteins do not return to the cytosol.
True.
268
ER signal sequences are directed to the ER membrane by the ___1___ and the ___2___.
1. SRP - signal recognition particle * in the cytosol that binds to the ER signal sequence
2. SRP receptor/docking protein embedded in the ER membrane.
269
For soluble proteins, ER sequences are almost always where?
At the N-terminus
270
Respiratory infections by M. tuberculosis and M. kansaii have similar symptoms and drug susceptibility profiles. What reason is there to bother differentiating between the two?
Different epidemiology. M. Kansaii is from the environment and non-communicable. M. Tuberculosis requires tracing of other contacts to control its spread.
