SNAPP Week 1: Concepts and Questions

Question 1

Which of the following is an expected result of a drug that enhances the action of normal p53 in response to ultraviolet exposure?

Answer 1

Increased apoptosis in damaged cells.

-p53 is a tumor suppressor gene so it arrests the cell cycle, promotes DNA repair and induces apoptosis in damaged cells.

Question 2

Which of the following is a true statement regarding the regulation of cholesterol synthesis?

Answer 2

Insig binds SCAP only when cholesterol is high.

• SREBP needs to move into the Golgi to be cleaved and released as a transcription factor.
• Insig binds SCAP when cholesterol levels are high, this complex blocks SCAP signaling.
• SCAP signal domain is recognized by COPII for vesicles to move from ER to Golgi.
• As cholesterol concentration drops, Insig no longer binds SCAP and SCAP/SREBP complex gets packaged into vesicles to go to the golgi.

Question 3

Which of the following is true regarding the body’s normal pH levels?

Answer 3

Venous blood is more acidic than arterial blood.

• Veins carry more CO2 and are slightly more acidic than arteries
• The inside of cells is MORE acidic than the outside.
• Blood pH = 7.4, [H+] = 40nmol/L
• The major regulatory organs are the kidneys and the lungs.
• Venous blood pH = 7.28-7.42
• Arterial blood pH = 7.34-7.44

Question 4

You calculate the pKa for a compound and find it to have an extremely high value. Without knowing anything about the compound, which of the following conclusions is most correct?

Answer 4

It is a strong base.

-High pKa = strong base
-Low pka = strong acid
-pKa indicates the tendency of a species to be a proton donor (acid) or acceptor (base)
pKa = -log ([H+][A-] / [HA])
-think pKa = -log (dissociated concentration/undissociated concentration)

Question 5

If you wanted to calculate the pH of a given solution and had the pKa, the concentration of the base, and the concentration of the acid, which equation would you use?

Answer 5

pH= pKa+log ([base]/[acid])

This is the Henderson Hasselbalch equation. In the question stem, you have ever variable except for the pH. This would be the appropriate equation to use.

Question 6

Your Aunt Betty came over last night asking for help from her ‘soon to be doctor.’ She says she had a stomach ache last night and took some antacids, but is worried that she may have taken too many. Assuming she is correct, which of the following physiologic functions has been impaired?

Answer 6

facilitation of passive diffusion of plasma across the mucosal barrier.

• Low pH of gastric juice facilitates passive diffusion of plasma across mucosal barrier
• H. Pylori is a bacteria that can thrive in the gut because it uses urease to neutralize its environment. –For ionizing drugs, uptake can be determined by pH of local environment

Question 7

If [A-]/[HA] = 2, what percentage of the solution is deprotonated?

Answer 7

66% (2/3) If [A-]/[HA] = 2 then you know that there are 2 A- molecules for every HA The deprotonated:protonated ratio is 2:1. Therefore, 2/3 are deprotonated. (Note: the number 3 comes from adding [A-] and [HA-] to account for the whole solution.

Question 8

As a result of ketoacidosis, blood HCO3- concentration is reduced from 24 to 8mM. Hyperventilation causes pCO2 to drop to 15mmHg. What is the patient’s blood pH?

Answer 8

7. 3

7. 3 pH = 6.1 + log (8mM)/(.03x15) = 7.34

Question 9

Which of the following is a characteristic of malignant tumors but NOT a characteristic of benign lesions?

Answer 9

metastatic.

benign tumors are not invasive or metastatic but they are:

• undifferentiated
• unresponsive to growth control signals
• immortalized

Question 10

p53, BRCA1 and BRCA2 mutations are considered risk factors for cancer because they:

Answer 10

encode DNA repair factors

p53, BRCA1 and BRCA2 encode DNA repair factors

Question 11

Which of the following is true regarding the APC (adenomatous polyposis coli) gene?

Answer 11

loss of heterozygosity is associated with Familial Adenomatous Polyposis.

loss of heterozygosity is associated with FAP It has a dominant inheritance pattern APC (adenomatous polyposis coli) is a tumor suppressor gene individuals who are born as heterozygotes are at increased risk but normal individuals will need 2 mutations in the same cell to develop cancer (odds are much lower)

Question 12

In the presence of elevated CDK (Cyclin-Dependent protein kinase) levels:

Answer 12

more cells will proceed into S phase.

increasing CDK will decrease RB (Retinoblastoma) inhibition (double negative by phosphoralating) and more cells will proceed from G1 into S phase (proliferation)

Question 13

An 8 year old patient is diagnosed with a unilateral retinoblastoma in her right eye. A biopsy and genetic sequencing of normal tissue surrounding the tumor is homozygous for the RB (Retinoblastoma) gene, with normal protein expression. Which of the following findings is MOST likely, given this patient’s history and exam findings?

Answer 13

both copies of RB (Retinoblastoma) are inactivated in tumor cells.

Unilateral retinoblastomas indicate a spontaneous RB mutation. Since the surrounding normal tissue is expressing normal RB protein levels, the patient does not have familial RB heterozygosity. Retinoblastoma cells will be homozygous for mutated RB , but all other cells will be homozygous for normal RB. Bilateral retinoblastomas are rarely the result of spontaneous mutations because the likelihood of a single cell getting 2 mutations to RB is rare and will probably not occur in more than one place. Bilateral retinoblastoma is a trademark of familial RB.

Question 14

Which of the following correctly describes the function of the protein normally transcribed by APC (adenomatous polyposis coli) gene?

Answer 14

degradation of free Beta-catenin in the cytoplasm.

APC codes for a protein that degrades free beta-catenin If APC is lost, free beta catenin will go to the nucleus and produce c-myc oncogenes Beta-catenin is normally held outside the nucleus by E-cadherin

Question 15

BRCA1 and BRCA2 code for proteins involved in which of the following functions?

Answer 15

DNA repair.

BRCA1 and BRCA2 are involved in DNA repair Inherited BRCA mutations exhibit LOH, but acquired cases do not. Other genes likely influence BRCA function indirectly

Question 16

Mutations to p53 are present in what percentage of all cancers?

Answer 16

50% .

50% of all cancers have a p53 mutation. However, 100% of all cancers have mutations that either directly alter p53 or interfere with one of its pathways.

Question 17

95% of p53 mutations alter p53 function by:

Answer 17

inhibiting the DNA binding domain

95% of all p53 mutations inhibit its binding domain (so p53 can’t bind DNA)

Question 18

Human Papilloma virus is an oncogenic virus in humans meaning that it:

Answer 18

inhibits p53 and RB (Retinoblastoma).

oncogenic viruses inhibit RB (Retinoblastoma) and p53

Question 19

Which of the following correctly characterizes the genetic basis of Retinoblastoma?

Answer 19

autosomal recessive disorder with a dominant inheritance pattern

recessive disorder (requires 2 hits) but has a dominant inheritance pattern
A single cell that has lost heterozygosity will turn into a tumor.
 Familial cases = 36% of the time 
bilateral Spontaneous = 6% of the time is bilateral Surgically repaired

Question 20

A cell that is homozygous for mutated RB (Retinoblastoma gene) is in S phase of the cell cycle. If a signal from outside the cell arrives to the plasma membrane in order to trigger inhibition of cell growth, which of the following will occur?

Answer 20

the cell to continue to divide.

if RB (Retinoblastoma) is mutated, it is constitutively turned off, and the cell is free to proliferate without regulation. The outside of the cell can no longer communicate with the inside and RB (Retinoblastoma) cannot be activated. In normal cells, if you want to divide you must turn off RB (Retinoblastoma)

Question 21

p53 mutations are most often:

Answer 21

missense.

p53 mutations are mostly missense (75%)

Question 22

Internal virion proteins are encoded by which type of viral gene?

Answer 22

gag.

-gag: codes for internal virion proteins
-env: encodes for membrane glycoproteins
-pol: encodes for reverse polymerase
v-myc: mimics the c-myc proto-oncogene (cell growth/division)

Question 23

If the RB (Retinoblastoma) protein is hypophosphorylated in a cell, what will happen?

Answer 23

the cell will be arrested in G1 phase.

-hypophosphorylation means RB (Retinoblastoma) is active and cells cannot go from G1 to S phase of the cell cycle

Question 24

A cell containing only water and 300mM of a non-permeating protein is placed in a solution of 600 non-permeating sucrose. The membrane is permeable to water. What will be the volume of the cell (relative to its initial volume) after all net fluxes have stopped?

Answer 24

the cell will be 1/2 its initial volume

the cell will shrink to 1/2 its initial volume, at which point the osmolarity inside will equal the osmolarity outside, which is another way of saying that the concentration of water on the two sides is the same

Question 25

A cell containing only water and 300mM of a non-permeating protein is placed in a solution of 300 mM non-permeating NaCl, and 600 permeating glycerol. The membrane is permeable to water. What will be the volume of the cell (relative to its initial volume) after all net fluxes have stopped?

Answer 25

the cell will be 1/2 its initial volume

the cell will shrink to 1/2 its volume. 300 mM NaCl - 600 mosM solution of Na and Cl ions [See above for explanation] You can ignore glycerol completely.

Question 26

Which of the following DKA patients has the lowest risk for cerebral edema?

Answer 26

a 10 year old diabetic diagnosed 5 years ago

established diabetics have less risk of cerebral edema than new onset.

• Risk factors for cerebral edema:
• Administration of bicaRB (Retinoblastoma)onate
• insulin during first hour
• smaller than normal increase in Na
• increased volume of fluid treatment increases risk.

Question 27

Which of the following is a result of insulin release from pancreatic beta cells?

Answer 27

increased storage of glycogen in the liver.

-insulin increases caRB (Retinoblastoma)ohydrate storage as glycogen in the liver

insulin release:

• Decreases lipolysis
• decreases gluconeogenesis (liver)
• Inhibits ketone body formation
• Increases FA storage as triglycerides
• Signals cellular uptake of glucose

Question 28

An 8 year old boy presents to your office for increased work of breathing. His parents explain that he has been complaining of increased thirst and urination for the past 3 weeks. He has lost 8 pounds since his last visit and his breath smells slightly fruity. After doing initial blood work, you find a venous pH of 7.04. You proceed with a urine analysis. Which of the following findings is most likely?

Answer 28

increased K+

These are classic findings for Diabetic Ketone Acidosis (confirmed by lower than normal pH). The increased levels of H+ will be cause H+ to be exchanged for K+. Potassium will come out of cells and then be excreted in the urine. Thus the patient can become hypokalemic even though initially their levels of K+ seem normal if not high (all the potassium is extracellular and the cells are being depleted of it).

Question 29

What is the best explanation for the rationale behind slow administration of insulin?

Answer 29

to avoid rapid cellular fluid uptake.

During DKA, potassium is exchanged for hydrogen and ions and then lost in the urine. Treatment with insulin improves the acidosis and drives the potassium intracellular. This increase in intracellular K+ increases the osmotic pressure and therefore water is likely to be driven into the cell. If this fluid intake happens too rapidly, cerebral edema can occur. A is not correct because although osmotic diuresis happens during DKA, it is not a result of the treatment.

Question 30

Which of the following best describes the correct distribution of fluid in the human body?

Answer 30

27 L inside of cells,
18 L outside of cells

the two major fluid compartments are the intracellular (2/3 of total=27 liters) and extracellular (1/3 total=13 liters + 5 liters (from the ‘third space’)

Question 31

Extracellular fluid (ECF) and intracellular fluid (ICF) differ in their ionic composition . Which of the following correctly describes the ionic concentrations of sodium, potassium and chloride ions of the intracellular fluid?

Answer 31

[Na+]i < [Na+]o; [K+]i > [K+]o; [Cl-]i < [Cl-]o

These are relative values that are important to know. There is a helpful chart on the second page of Dr. Betz’s ‘Composition of Cells’ lecture notes. One rule of thumb is that blood is table salt, cells are PP (Potassium Protein)

Question 32

A soldier is stranded and starving in the desert. Because of his starvation, he has become less capable of producing ATP. As a result his Na+/K+ transporter is affected. Which of the following effects would a compromised Na+/K+ pump have on his cells?

Answer 32

The resting membrane potential will move towards the sodium equilibrium potential.

The Na+/K+ pump pumps Na+ out of cells and K+ into cells [to actively maintain a negative membrane potential.- this is an incorrect upshot of the Na/K pump activity. Resting membrane potential is primarily determined by relative membrane permeability. The pump creates the ‘batteries’ for Na and K If this were non-functional, Na+ would flow into the cell unopposed and K+ would flow out of the cell (down their respective electrochemical gradients). Because there is an increased concentration of Na+ in the cell, the sodium equilibrium potential will be closer to zero (because the concentrations inside and out are more nearly equal to each other) If membrane permeabilities to ions do not change, then the membrane potential will stay in its same position relative to the equilibrium potentials, and because they (the equilibrium potentials) are moving towards zero, so will the membrane potential and the cell will depolarize.

Question 33

A 30-year-old man presents to the ER with heart palpitations and is unable to move his arms and legs. You suspect hyperkalemia so you order a complete metabolic panel. Sure enough, his serum potassium is elevated. What percentage of potassium has likely leaked from the intracellular compartment into the extracellular compartment?

Answer 33

2% .

Ionic balance and maintenance is so important that as little as a 2% K+ leakage into ECF can be fatal (hyperkalemia as in this example), if the leakage occurs rapidly or if renal function is compromised.

Question 34

Most ions and molecular compounds are pumped. However, there are two compounds for which pumps have not evolved; they always move passively across membranes What are they?

Answer 34

Urea and H2O

Urea and water are not pumped anywhere in the body as they Always move down their respective concentration gradients.

Question 35

Which of the following drugs have been shown to DECREASE serum K?

Answer 35

loop diuretics.

-diuretics increase excretion, so would decrease K

Things that increase blood potassium:

• ACE inhibitors
• ARB (Retinoblastoma)s
• NSAIDS
• heparin, and drugs that contain K
• Dietary K also contributes

Question 36

K redistribution can cause hyperkalemia because K shifts from the cells into the ECF. Which of the following will promote potassium reuptake into cells?

Answer 36

beta agonists.

• Beta agonists promote K uptake into cells
• Beta blockers impair K movement into cells
• Insulin deficiency/resistance impairs K movement into cells
• Acidosis causes H+ to move into the cell in exchange for K so ECF potassium goes up.
• ACE inhibitors, NSAIDS, etc. don’t shift K out of cells. They increase serum K by reducing excretion.

Question 37

Where does aldosterone act on the kidney?

Answer 37

collecting duct

Aldosterone acts at the collecting duct. Aldosterone increases K excretion. Aldosterone is low in diabetics and activity is decreased by ACE inhibitors and ARB (Retinoblastoma)s

Question 38

Which of the following is the most serious symptom of HYPOkalemia?

Answer 38

cardiac arrhythmias

arrhythmias are the most serious symptom. 
Presenting symptoms = 
-low BP
-high HR
-decreased appetite
-diarrhea
-low K Replete

give K. If this doesn’t work, you should suspect Mg depletion
Don’t give K too fast because you can cause an arrhythmia

Question 39

A patient presents to your clinic with hyperkalemia caused by rhabdomyolysis. Why are you concerned about decreased kidney function?

Answer 39

Myoglobin is toxic to kidneys.

Rhabdomyolysis causes myoglobin and potassium to be released into blood stream.
-This is toxic to kidneys.
-causes glomerular filtration rate to decrease so less K can be excreted.
The result is hyperkalemia and metabolic acidosis (blood pH 7.35).

Question 40

A 42-year-old female presents to your clinic with bloody discharge from her left nipple. After genetic testing, a p53 mutation is confirmed. In order to narrow your differential diagnosis, you begin to ask her about her family history. Which of the following details of her family history is most consistent with a Li Fraumeni Syndrome diagnosis?

Answer 40

Her 40-year-old sister and her 20-year-old daughter both have ovarian cancer

Diagnostic Criteria for Li Fraumeni Syndrome:

• Proband with sarcoma before 45
• 1st degree relative with cancer before 45
• 1st or 2nd degree relative with cancer before 45, or sarcoma at any age

Question 41

Knudson developed his “two hit” theory based on the idea that both copies of a chromosome are mutated:

Answer 41

Separately, once in the germline and once over the lifetime of the individual

The “Knudson Two Hit” theory refers to a pre-malignant mutation that occurs initially in the genome of a person with a predisposition to cancer and the second mutation that happens during the lifetime of an individual, as a result of an environmental factor like radiation.

Question 42

Which of the following is a characteristic of SNARE proteins?

Answer 42

SNAPS and syntaxins are located on the target membrane.

-Molecular motor proteins carry and deliver the vesicles
-SNARE proteins are for the actual fusion of the vesicles.
-SNARES are soluble NSF attachment protein receptors (hence the S in SNARE)
There are three main classes of SNARES: VAMPS, syntaxins and SNAPS

Question 43

Which of the following correctly describes the function of NSF?

Answer 43

hydrolysis of ATP to disassemble the SNARE complex.

• NSF hydrolyzes 6 ATP to unwind and recycle the SNARE complex so that it can be reused.
• A is referring to botulinum toxin (cleaves SNAREs, prevents NT release, paralysis)
• C is not correct because NSF deactivates SNARE so that it can be recycled and re-used.
• D is not correct because nucleation and zippering are the steps of membrane fusion where SNARE is active. NSF functions during recycling.

Question 44

If you wanted to design a drug that would prevent the refolding of SNARE back into its active confirmation, which of the following proteins would you want the drug to inhibit?

Answer 44

Sec1.

Sec1 proteins refold SNAREs into their active conformation (binds to/acts on syntaxin)

Question 45

Which of the following characteristics is common to all three classes of SNARE proteins?

Answer 45

a helical domain.

• All SNARE proteins have at least one helical domain
• While SNAP actually has two helical domains
• However SNAP does not have a transmembrane domain so this is not a characteristic they all share.
• Only VAMP is carried in vesicles
• only SNAP and syntaxin are located in the target membrane.

Question 46

If ATP were cut off from a cell, which of the following membrane proteins would no longer be able to function?

Answer 46

primary and secondary active transport systems

as well as Na/K pumps!

-if no ATP, the primary pumps won’t work, which means they will not generate any potential energy for secondary pumps to be able to work either. Secondary transport depends on Na leakage into the cell, and metabolism

Question 47

Which of the following substances will not dissociate in a solution?

Answer 47

(NH2)2CO

urea will not dissociate (neither will glucose), all the others will

Question 48

For every solute particle in the plasma, there are how many water molecules?

Answer 48

• the concentration of water in plasma is 55,555 mMol.
• the total solute osmolarity of plasma is approximately 300 mMol.

55,555/300 is around 185, so 150 is the best answer.

Question 49

What is the osmolarity of a 35M solution of KCl?

Answer 49

70 osM

70 osM 1K, 1Cl = 2osM/L x 35L = 70 osM

Question 50

You create a solution that makes a cell shrink. Without knowing more, you can conclude that

Answer 50

the solution is hypertonic

Question 51

Suppose we have a cell that is permeable to Cl-, with a higher concentration of Cl in the ECF than in the cell. What will be the sign of the Cl equilibrium potential?

Answer 51

negative

a negative Ecl will be necessary to repel C and keep it from diffusing into the cell down its concentration gradient

Question 52

A cell in a steady state contains 200mM of a neutral nonpermeating protein. The cell membrane is impermeable to Na+ but permeable to Cl-. If there is 200mM Na in the ECF, what is the total osmolarity, Na+ and Cl- concentrations inside the cell?

Answer 52

total osmolarity = 400, Na = 100, Cl = 100

total osmolarity = 400, Cl = 100, Na = 100 Make this table from the question and then fill it in: Na = ____ (-) 200 Cl = _____ (+) ___ P = 200 (-) ____ Total osM= ___________ You know there must be 0P outside the cell, and 200 Cl outside to balance the charge, which means total osmolarity outside and inside must be 400. This means you have 200 osm to split evenly between Na and Cl inside the cell. So 100 Na, 100 Cl inside.

Question 53

During clysis, 300mosM glucose is administered subcutaneously to an infant. Why does a blister grow, but eventually disappear?

Answer 53

the reflection coefficient of glucose is greater than the reflection coefficient of NaCl.

the reflection coefficient of glucose is greater than that of NaCl meaning that the injected solution will exert a larger osmotic force than NaCl, as so water will move from the blood to the blister. Let’s say the reflection coefficient for glucose = .5, then the osmotic forces are: ICF = 300, ECF = .5(300) = 150 (Hypotonic so water will flow out of the blood) Eventually, glucose will diffuse into the blood and be carried away, and the blister will disappear.

Question 54

A cell containing 300 mosM of non-permeating ions is placed into a solution containing only 300 mosM solute with a reflection coefficient of 0.5. What will happen to the cell?

Answer 54

it will swell eventually

it will swell eventually. A reflection coefficient of .5 means that the solute can get into the cell half as easily as water. Osmotic pressure is given as:\Pi:=\sigma RT\Delta C:
thus, the osmotic pressure due to the solute inside of the cell (which cannot cross the plasma membrane, so sigma = 1) is RT(300) and the osmotic pressure due to the solute outside of the cell is 0.5RT(300) = RT(150), only half as strong as the pressure pulling water into the cell. This has the net effect of drawing water into the cell as the extracellular solute (to which the membrane is somewhat permeable) diffuses into the cell.

Question 55

If urea has a reflection coefficient of zero, what is the osmotic driving force for H20 to enter this cell?
Solute	[ICF]	[ECF]	Permeable?
Na+	        100  100  No
Urea	100	0	Fully
Glucose	100	0	No

Answer 55

100*RT

100 mosM If the reflection coefficient for urea =0 then it does not exert any osmotic force. Thus, there is a 100 mosM difference between ECF and ICF and water will move into the cell with an osmotic driving force of 100 mosM

Question 56

If a cell is a steady state has a Vm = -80 mV, and the concentration of H+ out = 50 nM, and H+ in = 100 nM, Which of the following must be true?

Answer 56

H is being pumped out of the cell.

H is pumped out. Vm = -80 mV E = 62log (50/100) = -18 mV

Question 57

If a cell’s Vm = -40 mV, and the concentration of Na out = 140 and Na in = 14, which of the following must be true?

Answer 57

Na is being pumped out of the cell.

Na is pumped out. Vm = -40 E = 60log(140/14) = +60

Question 58

A transporter in the proximal convoluted tubule of the kidney expels a bicaRB (Retinoblastoma)onate ion into the lumen of the tubule, while a chloride ion moves from the lumen into the cell. No ATP molecules are split in the process. Rather, energy from the downhill leak of sodium ions into the cell is what drives this transporter. Based on this information, you know this transporter must be which of the following?

Answer 58

exchanger

Exchangers and antiporters are secondary active transport pumps that move two ion species in opposite directions. Co-transporters are secondary active transporters that move two ion species in the same direction. Co-transporters and exchangers are examples of secondary active transporters meaning their energy is NOT derived from the direct splitting of ATP but is instead derived from the downhill flow of sodium ions into cells.

Question 59

Which of the following would make hyperkalemia a more serious problem in a patient?

Answer 59

kidney failure

kidney failure because normally the kidney would excrete excess K

Question 60

On your first day at preceptor, a patient presents to the emergency department of Denver Health with a serum potassium of 9.0 (normal range: 3.5 to 5). Thanks to Molecules to Medicine, you distinctly remember that intracellular potassium is actually low in the patient, despite a high serum K reading. Of the following drugs that should be given to this patient, which ones function to stimulate the uptake of extracellular potassium into cells?

Answer 60

insulin and glucose

glucose/insulin administration will encourage cells to take up K from the extracellular fluid by providing extra energy in the form of ATP for the Na/K pump (a primary active transporter).

Question 61

A cell sequesters amino acids in its cytoplasm via secondary active transport. What would happen to the concentration of amino acids if extracellular sodium is reduced so that Na inside the cell equals Na outside the cell?

Answer 61

net uptake of amino acids will stop

amino acids will stop entering the cell because secondary active transport relies on the Na/K pump. Decreasing ECF Na will inhibit the Na/K pump because the inward leak of Na ions into the cell will be reduced, thereby reducing the potential energy available for secondary active transport. Many substances in the body are pumped via secondary active transport.

Question 62

By studying cases of familial VHL disease, the phenotypic implications of VHL inactivation were established. Which of the following is not manifestation of familial VHL disease?

Answer 62

Spelnic cysts.

The manifestations of VHL are largely vascular, fitting with the impact of the mutation, noting that renal cell carcinomas are especially vascular tumors.

Cysts frequently arise in the kidneys, pancreas, and liver, but not in the spleen.

So what you do get apparently is renal cell carcinoma, hemangioma, and angiomatosis retinae

Question 63

Sorafenib and sunitinib are drugs that target which of the following?

Answer 63

VEGF-Receptor and PDGF-Receptor

VEGF and PDGF are targeted by drugs that treat renal cell carcinoma (physiology was understood based on VHL disease) Drugs aren’t very targeted so they inhibit a lot of other stuff besides kinases.

Question 64

What is the inheritance pattern for von-Hippel Lindau?

Answer 64

Autosomal dominant

Autosomal dominant Heterozygous genotype is inherited 1/36,000 births (rare)

Question 65

Which of the following is the most common cause of death in patients with von-Hippel Lindau Disease in the modern era?

Answer 65

Renal cell carcinomas

Renal cell carcinomas All others are common manifestations of VHL, but do not commonly cause death Disease manifestations = multiple vascular tumors on the same organ

Question 66

In normally functioning cells, which of the following is observed?

Answer 66

If O2 level decrease, Hif1 alpha will not be ubiquitinated and will promote vascularization.

If O2 level decrease, Hif 1 alpha will not be ubiquitinated and will induce vascularization. In normal cells, VHL forms a multiprotein complex (heterodimer) that targets hif1 alpha for degradation via ubiquitination. If VHL is dysfunctional, Hif 1alpha is not targeted for degradation and it is able to form a heterodimeric transcription factor that promotes expression of hypoxia inducible genes such as VEGFR and PDGFR. The resulting unregulated vascularization results in vascular tumors seen in the clinical presentation of Von-Hippel Lindau disease.