Unit 3

Question 1

Describe at least five different properties of malignant cancer cells.

Answer 1

(1) Altered morphology
(2) Loss of contact inhibition
(3) Ability to grow without attachment to solid substrate (anchorage independence)
(4) Ability to proliferate indefinitely (immortalization)
(5) Reduced requirement for mitogenic growth factors
(6) High saturation density
(7) Inability to halt proliferation in response to deprivation of growth factors
(8) Increased transport of glucose
(9) Tumorigenicty

Question 2

Describe the multi-step process for carcinogenesis, and discuss the relative importance of heredity and the environment and why early events may include mutations in DNA repair genes.

Answer 2

Increased proliferation
Early neoplasia
Progressive neoplasia
Carcinoma
Metastasis

Fidelity of tumor suppression genes is critical to keep the cell cycle in check. When this function is lost, cells can proliferate uncontrollably.

Early exposure to carcinogens can lead to further mutations later in life.

Question 3

Discuss the types of genes usually mutated in tumor initiation and their effect on cellular proliferation.

Answer 3

Oncogene: Drives proliferation (quantitative or qualitative changes)

Tumor Suppressors: Inhibit cancer (molecules that inhibit proliferation or metastasis)

Question 4

Describe at least two different examples for the type of cytogenetic abnormalities associated with malignancy.

Answer 4

BCR-ABL: BCR gene contains a strong promotor and ABL gene is a protein kinase which drives cell proliferation. (Philadephia Chromosome) - Causes CML

Retina blastoma: Loss of heterozygosity because one gene will be mutated at birth. When cells divide, mitotic recombination can lead to one cell getting both mutations knocking out the RB1 gene (a tumor suppressor).

Question 5

Give at least two examples of events that can produce loss of heterozygosity and how they support Knudson’s theory.

Answer 5

(1) Mitotic recombination
(2) Tumor viruses targeting tumor suppressors (RB, p53)

Supports Knudson’s theory of just needing “one additional hit” to get cancer.

Question 6

Describe how cancers are associated with both dominant and recessive syndromes.

Answer 6

For loss of function (tumor suppressors) inheritance is in a dominant manner. However both genes need to be lost (during mitotic recombination) to be affected which behaves in a recessive manner.

Question 7

List at least three biochemical properties of the protein product of the RB gene.

Answer 7

(1) stabilizes constitutive heterochromatin to maintain the overall chromatin structure
(2) hypophosphorylated form of the protein binds transcription factor E2F1
(3) Recruits and targets histone methyltransferases, leading to epigenetic transcriptional repression

Question 8

Describe how the RB protein functions during the cell cycle and why it is important in cancer; specifically how the loss of RB may produce a malignancy.

Answer 8

RB gene blocks the cell cycle from moving from the G1 phase to the S phase of the cell cycle.

Question 9

Describe the hallmark of a tumor suppressor gene or anti-oncogene and how this relates to the RB gene.

Answer 9

Tumor Suppressors: Inhibit cancer (molecules that inhibit proliferation or metastasis). The RB gene is a tumor suppressor so in the case of homozygous loss of this gene, the cell has a high chance of becoming cancerous.

Question 10

Explain why APC, BRCA1 and BRCA2 genes are tumor suppressors.

Answer 10

APC, BRCA1 and BRCA2 inhibit cell cycle:

APC: Beta-catenin, is regulated by the APC protein through the Wnt signaling pathway. Regulation of beta-catenin prevents genes that stimulate cell division from being turned on too often and prevents cell overgrowth.

BRCA1: regulates cell cycle when there is DNA damage. Either leads to DNA repair or apoptosis.

BRCA2: important to binding Rad51 which is important in recruiting sister chromosome to for homologous recombination.

Question 11

Describe why p53 was originally incorrectly thought to be an oncogene.

Answer 11

Because cells which are heterozygous for p53 mutations result in cancer. This is because the active form of the protein is a tetramer of four “good” proteins. When one protein is misformed, it kills the functionality of p53.

Question 12

Explain why p53 is the “guardian of the genome.”

Answer 12

In its anti-cancer role, p53 works through several mechanisms:

(1) Activate DNA repair proteins when DNA has sustained damage.
(2) Arrest growth by holding the cell cycle at the G1/S regulation point to allow for DNA damage repair
(3) It can initiate apoptosis if DNA damage proves to be irreparable.

Question 13

Describe the cellular function of the p53 protein.

Answer 13

p53 is a transcription factor which identifies then binds to a promotor region.

Question 14

Recognize HPV (human papilloma virus) as an example of an oncogenic virus in humans

Answer 14

HPV produces two proteins: E6 and E7. E7 binds RB and inactivates it. E6 binds p53 and causes it to be degraded.
HPV also integrates into the DNA of a cell and destroys the E1 repressor which turns on E6 and E7.

Question 15

What is oncogene dependence?

Answer 15

When a tumor requires a product of a mutation in order to survive.

Question 16

Explain the Wnt2 pathway

Answer 16

Wnt (growth factor) binds Frizzled

Bound Frizzled releases beta-catenin from cytoplasm into nucleus

Beta-catenin activates the TCF transcription factors

TCF turns on an oncogene called c-myc

Question 17

What percentage of cancers include p53 mutations?

What is the most common type of p53 mutation?

Answer 17

~50%

missense (~75%)

Question 18

What is a dominant negative mutation?

Answer 18

A mutation that occurs when one miscoded protein can result in an inhibitory effect for other interacting proteins/molecules.

Question 19

What is c-myc?

Answer 19

Myc protein is a transcription factor that activates expression of many genes through binding enhancer box sequences and recruiting histone acetyltransferases (HATs). It can also act as a transcriptional repressor.

Question 20

Discuss the functions of protein products of viral oncogenes, including at least four examples of oncogenes of known function.

Answer 20

(1) v-src gene codes for a membrane bound protein
kinase that phosphorylates tyrosine residues in several different proteins, affecting gene expression.
(2) v-erb-B codes for a protein that is similar in structure to the cell surface receptor for epidermal growth factor (EGFR). This raises the possibility that this protein has growth stimulating properties like EGFR.
(3) v-abl codes for a protein kinase that phosphorylates tyrosine residues on other proteins. Similar to c-ABL
(4) v-myc - This gene is usually fused with a portion of the gag gene. It appears that this gene is capable of eliciting neoplastic transformation of cells.

Question 21

Describe why oncogenes are useful as molecular markers in prognosis

Answer 21

Oncogenes are gain of function mutations which cause hyper-proliferation in a cell. Using FISH to identify n-myc, for instance copy number can be identified. The higher the copy number, the worse the prognosis.

Question 22

Differentiate between oncogenes and tumor suppressor genes and describe the function of these two types of cancer genes and how mutations in them may combine to produce cancers.

Answer 22

Oncogenes: Gain of function
Tumor Suppressor: Loss of function

Both increased ability to proliferate (oncogene) and decreased regulation (tumor suppressor) lead to increasingly aggressive cancers.

Question 23

Describe two examples of how molecular, genomic, and clinical information (Bioinformatics) about a patient’s cancer are being used for targeted therapy and for “personalized medicine” in cancer.

Answer 23

Humanized Herceptin: Increases radiation efficacy (antibody binds to receptor Her2 (ErbB2) - oncogene)

Gleevec: Mimics ATP and fits only into ABL binding pocket (CML) so won’t interfere with other cellular functions.

Question 24

How are bioinformatics and personalized medicine used to treat cancer patients?

Answer 24

Diagnosis (malignant breast cancer)
Prognosis (poor - need therapy)
Therapy (high ER [Tamoxifen]; high ErbB2 [Herceptin])

Question 25

Describe the criteria for classifying a hereditary cancer syndrome as Li‐Fraumeni syndrome (LFS)

Answer 25

(1) Proband with a sarcoma diagnosed before the age of 45; and
(2) 1st degree relative with a sarcoma diagnosed before the age of 45; and
(3) 1st or 2nd degree relative diagnosed with any cancer before the age of 45

Question 26

Describe the Knudson two hit hypothesis.

Answer 26

Two mutations in a gene would be required to lead to the deactivation of a tumor suppressor (such as p53). The first hit is being born with a mutation on one allele. The second hit is the spontaneous mutation of the second allele.

Question 27

Describe the function of p53 in response to UV exposure.

Answer 27

p53 decides to shed off skin that is damaged by UV radiation. Skin is very regenerative so it can regrow cells.

Question 28

Describe the criteria for classifying a hereditary cancer syndrome as Li‐Fraumeni-Like syndrome (LFL)

Answer 28

(1) Proband with any childhood cancer, sarcoma, brain tumor or adrenal cortical tumor diagnosed before the age of 45; and
(2) 1st degree relative with a typical LFS tumor diagnosed at any age; and
(3) 1st or 2nd degree relative diagnosed with any cancer before the age of 60

Question 29

What are the common “hits” which activate cancerous states (two oncogenes; two tumor suppressors)?

Answer 29

Oncogenes
 - RAS
 - MYC
Tumor Suppressors
 - p53
 - pRB

Question 30

How does p53 work?

Answer 30

DNA damage, cell cycle abnormalities or hypoxia can stimulate p53.
p53 decides whether cell will go to cell cycle arrest (through Cdk2 and Cdc2), DNA repair and cell cycle restart or go to apoptosis.

Question 31

Recognize the clinical manifestations of Von Hippel‐Lindau (VHL) disease.

Answer 31

Formation of cystic-highly vascularized tumors.

• Cerebellar & spinal hemangioblastomas
• Retinal hemangioblastomas
• Bilateral kidney cysts and cc renal cell carcinomas
• Pheochromoctomas
• Pancreatic cysts and neuroendocrine tumors
• Endolymphatic sac (inner ear) tumors
• Cystadenomas of GI tract

Question 32

Recognize the molecular basis of Von Hippel‐Lindau (VHL) disease and the pathogenesis of clear cell renal cell carcinoma.

Answer 32

VHL is a tumor suppressor gene which targets unwanted proteins for proteosomal degradation by ubiquitination.

Protein

• Regulates HIF
• Suppresses aneuplody
• Stabilizes microtubule/primary cilia maintenance

Question 33

Define the rationale for therapies used to treat clear cell renal cell carcinoma.

Answer 33

Surgery to remove the offensive tissues

Radiotherapy to target specific masses to cause additional DNA damage in tumor cells.

Systemic therapy (targeted) to attack oncogenetic dependence)

Question 34

What is the inheritance pattern of von Hippel-Lindau syndrome?

Answer 34

Autosomal Dominant

Highly penetrant

High variable expressivity

20% of cases are de novo

Question 35

Define the following

• Hemangioblastoma
• Pheochromocytomas
• Endolymphatic sac tumors (ELSTs)

Answer 35

Hemangioblastoma: Tumors that originate from the vascular system
Pheochromocytomas: Norepinephrine -secreting tumors that can occur in adrenal gland
Endolymphatic sac tumors (ELSTs): tumors of the blind pouch in the inner ear.

Question 36

How is HIF controlled?

Answer 36

Oxygen dependent

Under normoxic conditions, VHL ubiquinates HIF-α marking it for proteosomal degredation

Under hypoxic conditions (or if VHL is mutated), VHL is unable to ubiquinate HIF-α.

Accumulation of HIF-α results in over-expression of (vascular endothelial growth factor) VEGF, (transforming growth factor) TGF, (platelet dependent growth factor) PDGF

Question 37

Describe the molecular components of a membrane.

Answer 37

Membrane phospholipid bilayer (hydrophilic heads and hydrophobic tails)

Cholesterol

Question 38

Describe the concept of membrane fluidity.

Answer 38

Membrane fluidity refers to the ability of phospholipids to move around in the bilayer

Question 39

Identify the parts of a phospholipid

Answer 39

(1) Glycerol backbone
(2) 2-fatty acid tails
(3) Polar phosphate/headgroup

Question 40

Identify the parts of a sphingolipid

Answer 40

(1) Sphingosine
(2) Fatty acid tail
(1) + (2) = ceramide
(3) Polar phosphate/headgroup

Question 41

Identify the parts of cholesterol.

Answer 41

(1) Hydroxyl group
(2) 4-ring hydrocarbon
(3) hydrocarbon tail

Question 42

Describe the asymmetry of membrane bilayers.

Answer 42

Asymmetry established in ER during synthesis

Functionally important as the headgroups react very specifically with various proteins.
- Different headgroups have different charge which affect the interaction

Question 43

List the different ways proteins associate with membranes.

Answer 43

Transmembrane proteins (single or multi α-helices or β-barrels)

Anchored membrane proteins (anchored by α-helices)

Attached to the bilayer by a covalently attached lipid chain (fatty acid chain or a prenyl group) or via an oligosaccharide linker, to phosphatidylinositol in the noncytosolic monolayer

Attached to the membrane only by noncovalent
interactions with other membrane proteins

Question 44

Explain how cholesterol synthesis is regulated.

Answer 44

1. When cholesterol levels are low SCAP-SREBP complex dissociates from Insig.
2. SCAP escorts SREBP to the Golgi by vesicular transport.
3. The bHLH transcription factor is released from SREBP by two step proteolysis- RIPRegulated Intramembrane Proteolysis
4. S1P is luminal, S2P is within the membrane – cleavage by both is required for activation
5. Nuclear bHLH SREBP moves to the nucleus, binds to DNA promoters, and activates many genes to produce more LDLR to bring cholesterol into the cell and to increase all the enzymes involved in cellular synthesis of cholesterol.

Question 45

What does cholesterol do in the lipid bi-layer?

Answer 45

(1) maintains membrane fluidity in changing temperature environments.
(2) increases membrane thickness

Question 46

What are the typical values for the volumes of plasma, extracellular fluid, ‘third space’, and intracellular fluid compartments.

Answer 46

Plasma: 3 liters
ECF: about 13 liters
‘third space’: 5 liters
ICF: about 27 liters

Question 47

Describe the major differences in ionic composition between ECF and ICF.

Answer 47

ECF: High Na+, Cl-; Low K+; no A-n
ICF: High K+, A-n; Low Na+, Cl-

Question 48

Describe the two most important functional properties of membranes, one conveyed by lipids, the other by channels and transporters.

Answer 48

Lipids: Impermeable to charged/polar substances and electrically strong.

Channels and transporters: Proteins which allow transmembrane movement of substances that wouldn’t otherwise be permitted based on signals or through actively pumping.

Question 49

Recite the routes by which a given substance can traverse a membrane.

Answer 49

Channels are selective proteins which allow transmembrane movement based on gated signals

Transporters move big molecules or actively pump molecules across the membrane (against gradient).

Question 50

Identify physical forces that can determine the gating properties of ion channels.

Answer 50

Temperature
Mechanical force
Chemical environment
Electrical potential

Question 51

What are the rules and assumptions which determine under a given set of conditions, whether a cell will swell or shrink.

Answer 51

1) ECF is constant
2) Only water determines change in volume
3) Water osmolarity (EC) = osmolarity (IC)
4) osmolarity of particular solute: [EC] = [IC] if membrane is permeable to solute

Question 52

List the three mechanisms that different cells have evolved to keep from swelling and bursting.

Answer 52

1) Cell impermeability to water
2) Cell wall (strong inelastic shell)
3) Osmotically

Question 53

Describe the difference between diffusion and osmosis.

Answer 53

Diffusion is a spontaneous movement of particles from an area of high concentration to an area of low concentration.

Osmosis is the spontaneous net movement of water across a semipermeable membrane from a region of low solute concentration to a solution with a high solute concentration, down a solute concentration gradient.

Question 54

Describe the effect of having a membrane with different, non‐zero permeabilities (i.e., reflection coefficients less than one) to different solutes.

Answer 54

Reflection coefficients dictate the rate that a solution with different solutes permeate across a membrane. A coefficient close to zero causes little osmotic pressure while a coefficient close to one causes high osmotic pressure.

Question 55

Define molarity, osmolarity, equivalents, and tonicity, and describe how to convert between them.

Answer 55

Molarity: the number of moles of solute dissolved in one liter of solution

Osmolarity: the total concentration of solute particles: for example, a 1 M solution of CaCl2 gives a 3 osM solution

Equivalents: the number of ‘combining weights’ of an ion per liter. Combining weight concerns acid-base titration (e.g., titrating 100 mM H2SO4 takes twice as much base as does 100 mM HCl, so SO4 has twice as many ‘combining equivalents’ per mole as Cl-).

Tonicity: The property of a solution that makes a cell shrink (hypertonic) or swell (hypotonic).

Question 56

Recognize the importance of sub‐cellular protein targeting.

Answer 56

Sub cellular protein targeting assures that specific vesicles only merge with targeted membranes.

Question 57

Describe the basic principles of membrane and viral fusion, including: a) the function and structure of SNARE proteins b) regulation of SNARE‐based fusion c) the mechanism of viral fusion d) the regulation of viral fusion.

Answer 57

(a) SNARE proteins form α-helix tetramers which force the membranes together
(b) NSF disassembles the tetramer and n-sec refolds synataxin and holds it in conformation until it is released.
(c) Viral envelope viruses fuse in the same way using SNARE protein homologues.

Question 58

Compare qualitatively the relative strengths of electric and osmotic forces.

Answer 58

The electric force is 10^18 times stronger than the osmotic force.

Question 59

Describe the two forces acting on an ion moving across a membrane.

Answer 59

(1) concentration difference
(2) membrane potential difference

The two forces, combined, make an electrochemical gradient.

Question 60

Define equilibrium potential.

Answer 60

The electrical potential difference across the membrane that must exist if an ion is to be at equilibrium.

Question 61

Describe the difference between an equilibrium potential and a recorded membrane potential.

Answer 61

While the equilibrium potential is the electrical potential required to maintain an ion at equilibrium, the actual recorded membrane potential could be different due to ion pumps.

Question 62

Determine if a pump for a particular ion must exist in a cell at rest (steady state), given an ion’s concentration inside and out, the membrane potential, and knowledge that the membrane is permeable to the ion in question; and, if a pump must exist,determine which direction it pumps the ion.

What is the formula?

Answer 62

E = (RT/zF) ln (Co/Ci) = 60 log [Co]/[Ci]

E= equilibrium potential
Co= outside concentration of the ion 
Ci= inside concentration
R= gas constant
T= temperature
z= valence of the ion in question;
F= Faraday constant.

Question 63

Answer correctly that the number of excess anions in a typical cell is small compared to the total number of anions.

Answer 63

Usually 1 part per 100,000

Question 64

Describe how an artificial cell can be in a state of equilibrium even though the concentrations of ions are not the same inside and out.

Answer 64

If a cell is permeable to only some ions, the movement of a small percentage of ions can create a large membrane potential difference causing concentration disequilibrium.

Question 65

Describe what ions are moved (and how many and in what direction) by one cycle of the sodium pump.

Answer 65

3 Na+ ions are pumped out

2 K+ ions are pumped in

Question 66

Differentiate between equilibrium and steady state.

Answer 66

Equilibrium indicates a state where no energy is required to maintain cellular ion concentrations whereas steady state indicates a state where ion concentrations are maintained but through the expenditure of energy.

Question 67

Describe how membrane potential depends on relative, not absolute, permeabilities to ions.

Answer 67

Relative permeability refers to the permeability of ions (in relation to each other) through a membrane. A membrane that is more permeable to K+ (leaving the cell down its concentration gradient) will have a negative membrane potential compared with one that is more permeable to Na+ (entering the cell) which will have a positive membrane potential. Capisce?

Question 68

Define Driving Force on an ion.

Answer 68

The difference between Vm (membrane voltage ) and the ion’s equilibrium potential. Positive ion potential across a negative membrane potential has a strong driving force (Na+ REALLY wants in)

Question 69

Describe why, in neurons and other excitable cells, membrane potential is sensitive to small changes in [K+]o, but not [Na+]o.

Answer 69

Small changes in [K]o is usually do to a leak from cells (from a large volume to small volume). This changes relative concentrations leading to change in Ek. Large changes in {Na]o doesn’t move [K]o greatly.

Question 70

Describe the law of mass action.

Answer 70

The rate of a reaction is proportional to the product of the concentrations of the reactants.

Keq = kf/kr = [Products]/[Reactants]

Question 71

Define pH and pKa.

Answer 71

pH - Negative log of [H+]. Measures acidity of a solution (lower = more acidic)
pKa - Negative log of the dissociation constant of an acid into its conjugate base and a proton. (lower = stronger acid)

Question 72

Write the Henderson‐Hasselbalch (H‐H) equation for any given weak acid or base.

Answer 72

pH = pKa + log [A-]/[HA]

Question 73

Define the H‐H equation for the bicarbonate buffer system in extracellular fluid and use it to evaluate clinical lab data.

Answer 73

pH = 6.1 + log [HCO3-]mM/ .03Pco2mmHg

Question 74

Define normal blood pH, [HCO3‐] and pCO2.

Answer 74

pH = 7.4 (7.35-7.45)
[HCO3-] = 24mM (22-26)
pCO2 = 40mmHg (35-45)

Question 75

Describe how weak acids and bases work to buffer pH and define the pH range of maximal buffering capacity.

Answer 75

Weak acid/bases are able to dissociate into their conjugates in order to buffer excess H+ or OH-. The pH range for buffers is approximately +/- 1.0 from it’s pKa.

Question 76

What is Inflammatory Bowel Disease (IBD)?

Answer 76

An inappropriate inflammatory response to intestinal microbes.

Question 77

What are the genetic and non-genetic contributing factors to IBD?

Answer 77

Genetic Factors:
 - nucleotide oligomerization domain 2 (NOD2)
 - Interleukin-23-type 17 helper T-cell (Th17) pathway
 - autophagy genes.
Non-genetic Factors:
 - Changes in diet
 - Antibiotic use
 - Altered intestinal colonization
 - tobacco

Question 78

How does diabetic ketoacidosis (DKA) present?

Answer 78

Polydipsia
Polyuria
Dizzy / altered mental status
Fatigue
Tachycardia
Tachypnea
Fasting glucose >125mg/dL, 2hr glucose > 200mg/dL

Question 79

Describe the major metabolic disturbances in DKA:
‐Elevated blood sugar (hyperglycemia)
‐Acidosis
‐Potassium derangements
‐Dehydration

Answer 79

Hyperglycemia: due to the body’s in ability to absorb glucose from the blood stream.

Dehydration: Excessive sugar in the blood gets excreted through urine, pulling water with it.

Acidosis: As a result of beta-oxidation. Byproducts are hydrogen ions and ketone bodies.

Potassium Derangements: Due to the body being dehydrated, the distal tubules hold onto Na+ to try to suck water back into the body. To keep balanced, the body releases K+. High H+ concentration influxes into the cells, at the expense of K+ efflux. Even though high K+ levels will exist in serum, the patient will need K+ when insulin is administered.

Question 80

Describe the stimulus for insulin release.

Answer 80

(1) Glucose enters the beta cells in the pancreas leading to increased ATP/ADP ratio (through glycolysis)
(2) which closes a K+ channel to cause rising intracellular K+
(3) increasing intracellular K+ depolarizes the membrane
(4) Calcium ions influx
(5) leading to insulin exocytosis

Question 81

Describe at least three target‐site actions of insulin.

Answer 81

(1) Liver – store glucose (as glycogen) and lipid, stop lipid and glycogen breakdown
(2) Muscle – store glucose, make protein
(3) Adipose – store glucose and triglyceride (incorporated into chains of fats)

Question 82

Describe the risk for cerebral edema in DKA.

Answer 82

Cerebral edema is the major cause of morbidity and mortality in DKA

May be present even before treatment starts, but some treatment factors can cause/exacerbate it:
- Rapid drops in glucose and sodium from too much or too hypotonic IV fluid cause fluid to osmotically enter the brain space.

Question 83

What is Cushing’s Triad

Answer 83

(1) Increased blood pressure
(2) Irregular breathing
(3) Reduction of HR

Question 84

Crohn’s vs. Ulcerative Colitis

• Hematochezia (bloody stool/diarrhea)
• Location
• Pattern
• Upper GI Tract
• Extra-GI manifestations
• FISTULAS
• Inflammation

Answer 84

Hematochezia (bloody stool/diarrhea)
 - Crohn's: Rarely
 - Ulcerative Colitis: Commonly
Location
 - Crohn's: Ileum
 - Ulcerative Colitis: Rectum
Patern
 - Crohn's: Discontinuous
 - Ulcerative Colitis: Continuous
Upper GI Tract
 - Crohn's: Yes
 - Ulcerative Colitis: No
Extra-GI manifestations
 - Crohn's: Common
 - Ulcerative Colitis: Common
FISTULAS
 - Crohn's: Common
 - Ulcerative Colitis: Rare
Inflammation
 - Crohn's: Transmural
 - Ulcerative Colitis: Mucosal

Question 85

Extraintestinal manifestations of IBD:

Answer 85

Sensorineural hearing loss
Pleuritis
Myocarditis
Pancreatitis
Pyoderma gangrenosum

Question 86

What are the components of DKA?

Answer 86

Diabetic: Hyperglycemia
Ketonemia and ketonuria
Acidotic

Question 87

How does Cerebral Edema present?

Risk factors?

How to treat?

Answer 87

Presents with mental status changes, headache, Cushing’s triad, fixed/dilated pupils.

Sicker or younger patients

Treatment is to raise the osmolality of the blood (Mannitol)

Question 88

What does Insulin do?

Answer 88

STORES ENERGY

• Make glycogen
• Make protein
• Make fat

Question 89

Describe the difference between primary and secondary active transport.

Answer 89

Primary active transport uses ATP as an energy source to pump ions across a membrane.

Secondary active transport uses the electrochemical gradient to drive transport.

Question 90

Define cotransport and exchange transport.

Answer 90

Co-transport: Transports a molecule along with the ion in the same direction.

Exchange transport: Transports a molecule in the opposite direction of the ion.

Question 91

Describe the non‐existence, but conceptually useful idea, of the H+/K+ exchanger.

Answer 91

There is no actual pump that exchanges H+ for K+ however the empirical evidence suggests that the concentrations of H+ and K+ in the ECF influence the uptake/excretion of the other.

Question 92

Describe how cells concentrate glucose inside, even though the glucose transporter cannot pump glucose against its concentration gradient.

Answer 92

Glucose is transported through facilitated diffusion.

Once inside, glucose is phosphorylated into glucose-6-phosphate G6P.

G6P is unable to fit into the transporter and doesn’t diffuse through the membrane.

Question 93

Describe two treatments for hyperkalemia by which cells can be encouraged to take up potassium from the ECF.

Answer 93

(1) Bicarbonate: lowers pH, pulling H+ out of cells and K+ in.
(2) Glucose/Insulin: Converted to ATP to drive Na+/K+ pump.

Question 94

What ion is the furthest away from its electrochemical equilibrium in the cell?

Answer 94

Ca++

Question 95

Describe the basic structure of Nav and Kv ion channels (number of subunits or repeats, number of membrane-crossing alpha helices per repeat/subunit) and whether this pattern is common to all known ion channels.

Answer 95

4 membrane-spanning domains

Each domain contains 6 α-helices

S4 helices have + charged residues (lys or arg) at
every third position which sense voltage

S5 and S6 helices, and the connecting “P loop”, assemble to form the ion conducting pathway and “selectivity filter.”

Question 96

Describe the basic principles of channel selectivity, the features of ions that are important for selectivity, and the role of dehydration of the ions.

Answer 96

Most channels are highly selective for their ions (some not as much). Selectivity depends on:

• Size of ion
• Charge (sign and valence)
• Dehydration of ions makes unmasks their true qualities making the pore more selective.
• Multiple binding sites can also increase selectivity

Question 97

Describe specific structures of Nav and Kv channels that serve as the voltage sensors.

Answer 97

S4 helix: Located on intracellular side of membrane. Rotational gate that senses the relative polarity of the membrane.

Question 98

Describe specific structures of Nav and Kv channels that serve as the voltage sensors, the selectivity filter.

Answer 98

within a central, ion conducting pathway formed by the four KV subunits or four repeats of NaV, where this central pathway is surrounded by S5 and S6 helices and connecting P loop contributed by the each of the four subunits or repeats.

Question 99

Describe specific structures of Nav and Kv channels that serve as the voltage sensors, the selectivity filter, and the activation/inactivation gates.

Answer 99

Activation Gates: a hinge-like motion of the S6 segments around a conserved glycine.

Inactivate Gates: formed by the cytoplasmic loop which
connects S3 and S4.

Question 100

Describe what structural features of Nav and Kv lead to “sidedness” of agents that act on these channels and to “state-dependence” of action.

Answer 100

Selectivity filter is located near the extracellular side

The vestibule is located near the intracellular side of the KV/NaV channels

The activation/inactivation gates are located near the intracellular side

Depending on the agents and their mechanism, they will work only when inside or outside the membrane wall.

Question 101

Describe the generic epithelial transport mechanisms for absorbing NaCl and water into the blood.

Answer 101

Na+/K+ pump exchanges Na+ ions (out) for K+ ions (in) on the basolateral side.

Na+ and Cl- freely enter the cell on the apical side down their electrochemical gradients.

Water follows the ions due to osmotic forces.

Question 102

Describe the basic transport mechanisms by which glucose and amino acids are absorbed into the blood.

Answer 102

Glucose and AAs are absorbed by epithelial cells through their apical membrane through a Na+ cotransporter using it’s electrochemical gradient (secondary active transport).

Glucose and AAs are then absorbed by the blood through facilitated diffusion through the epithelial cells basolateral membrane.

Question 103

Differentiate between ‘tight’ and ‘leaky’ epithelia.

Answer 103

Tight epithelia have impermeable junctions in between the cells.

Leaky epithelia have relatively permeable junctions in between the cells.

Question 104

Describe the basic process by which some epithelial cells secrete (rather than absorb) fluid.

Answer 104

Chloride channels are an example of how epithelial cells secrete ions/fluid through the apical membrane.

Cl- channel is normally closed.
When opened - Cl- leaks out bringing Na+ and water with it (intercellular shunt)

Question 105

Identify four important substances (water, O2, CO2, and urea) that are never pumped across membranes, but always move passively down their concentration gradients.

Answer 105

H2O: Always flows down it’s osmotic gradient

O2 and CO2: Non-polar gasses that diffuse through all membranes freely

Urea: Dumped into the glomerulus with everything else. The kidneys then reabsorb what they need, leaving urea and other waste products to be urinated out.

Question 106

Compare and contrast the relative roles of the G.I. tract (minimal) and kidney (extensive) in excreting non‐volatile
metabolic wastes and regulating ECF composition.

Answer 106

GI tract excretes mainly bilirubin (about 30 mMol/day).

Kidneys excrete all other non-volatile waste products.

Question 107

Describe how the passive electrical properties of axons render them poor conductors of electrical signals over distances greater than a few millimeters.

Answer 107

They leak ions so that when a cell start to depolarize, the ion leak to buffer the signal.

Question 108

Describe the positions of the activation and inactivation gates in sodium channels during an action potential.

Answer 108

At rest:
 - activation gates: closed
 - inactivation gates: open
Depolarization:
 - activation gates: open
 - inactivation gates: open
Repolarization:
 - activation gates: open -> closed
 - inactivation gates: closed
 - K+ channels: open

Question 109

Describe why intracellular concentrations of sodium and potassium do not change much after a single action potential.

Answer 109

This occurs when the neuronal cell volume is large compared with the surface area of the cell. While thousands of ions flow in and out, the relative volume of the cell compensates.

Question 110

Describe the role of the sodium/potassium pump during the action potential.

Answer 110

Na+/K+ pump restores the proper ECF/ICF concentrations to enable action potentials to recur.

Question 111

Describe the mechanisms underlying the refractory period of the action potential.

Answer 111

The refractory period is due to the inactivation gates of the Na+ channels opening slower than the activation gates.

Question 112

Describe the mechanisms underlying accommodation of the action potential.

Answer 112

Accommodation may occur when a slowly depolarizing cell allows sufficient time for the inactivation gates to close before a large number of activation gates open.

Question 113

Define the threshold for an action potential.

Answer 113

Threshold is when the current of Na+ ions into the cell equals the current of K+ ions out of the cell.

Question 114

Describe the positive‐feedback nature of the rising phase of the action potential.

Answer 114

Once threshold is met, Na+ ions start flowing into the cell faster than K+ ions flow out opening more gates, increasing the Na+ current.

Question 115

Describe how action potential propagation relies on voltage‐gated sodium channels acting like molecular “booster stations”.

Answer 115

As an action potential fires, it’s impulse propagates down the axon.

As the area depolarizes, the Na+ channels depolarize along the axon, firing again (boosting signal)

Unidirectional as once the AP fires, there is a refractory period that prevents the impulse from traveling backward.

Question 116

Discuss why action potential propagation is much slower than the velocity of light.

Answer 116

Resistance in the cell

Question 117

Describe how myelination increases action potential conduction velocity.

Answer 117

By disabling the current from dissipating out of the cell during an AP, myelin speeds the transmission of the signal directionally down the axon.

Question 118

Describe refractoriness, and explain how it prevents an action potential from reversing its direction of propagation.

Answer 118

“Refractoriness” is the characteristic of a potential to travel in only one direction down an axon.

Accomplished by inactivation Na+ channels disabling the ability of the impulse to travel back from the direction it came.

Question 119

Describe the effect of extracellular calcium ions on action potential threshold.

Answer 119

Extracellular Ca++ ions bind to negative charged polar headgroups on the exterior of the cell membrane.

This effectively hyperpolarizes the cell making it harder to reach potential threshold.

Question 120

Discuss the effect of axon diameter on conduction velocity, threshold to extracellular stimulation, safety factor of
conduction, and likelihood of being myelinated.

Answer 120

Velocity: Increased diameter = increased velocity

Threshold: Increased diameter = decreased threshold

Safety factor: Increased diameter = increased safety factor

Myelination: Increased diameter = increased myelination

Question 121

Describe basic clinical features of Multiple Sclerosis (MS).

Answer 121

Fatigue
Ataxia
Spasticity
Cognitive impairment
Bladder dysfunction
Pain
Mood instability
Sexual dysfunction

Question 122

Describe the consequences of demyelination in nerve conduction.

Answer 122

Prolonged conduction velocity

Question 123

Describe how certain therapies might improve nerve function.

Answer 123

K+ channel blocker - lowers threshold

Immune response modification

Question 124

Describe the structure of the nuclear pore complex

Answer 124

~30 distinct proteins
Repetitively arranged in sub-complexes
3 Distinct regions
 - Nuclear envelope
 - Scaffolding layer
 - Barrier layer

Question 125

Describe the basic mechanisms of how proteins and RNA/protein complex transport can be regulated.

Answer 125

Nuclear pore channel: NPC permeability; Nup expression

Transport receptor: Expression; sequestration

Cargo: Posttranslational modification; posttranscriptional modification; intermolecular/intramolecular interactions

Question 126

Explain how changes that impact nuclear transport and/or NPC components can contribute to disease.

Answer 126

DNA repair enzymes (BRCA 2, RAD51, P53) which cannot be imported into the nucleus or are transported out, blocking them from repairing the DNA.

Question 127

What are the roles of nucleoporins (Nups), karyopherins, and Ran in transport.

Answer 127

Nucleoporins: Transport water-soluble molecules across the nuclear envelope.

Karyopherins: Complex with proteins to transport them across the nuclear envelope (importins/exportins)

Ran: Interact with karyopherins enabling/disabling them from carrying cargo. They are either GDP (inactivated) or GTP (activated) bound.

Question 128

Describe the three mechanisms of protein transport.

Answer 128

to come

Question 129

List the major functions of the ER.

Answer 129

Synthesis of lipids
Control of cholesterol synthesis
Ca++ storage
Synthesis of proteins on membrane bound ribosomes
Co-translational folding of proteins
Post-translational protein insertion into membranes
QC

Question 130

Describe co‐translational translocation for the synthesis of cargo and transmembrane proteins.

Answer 130

Amino terminal end has a membrane signal sequence recognized by a signal recognition particle (SRP)

Ribosome pauses translation until SRP is bound by SRP receptor in ER.

[In the case of membrane bound, secondary signal sequences cause the ribosome to stop and generate proteins on opposite side of membrane]

Ribosome synthesizes protein through translocon in ER.

Signal peptidase degrades signal sequence.

Question 131

List the major functions of the Golgi.

Answer 131

Puts sugars and sulfates on proteins and lipids

Question 132

Name three well‐studied vesicle coats and describe how these coats function in vesicular transport.

Answer 132

COP I: Involved with the retrograde budding of vesicles off the Golgi back to the ER.

COP II: Involved with vesicles budding off of ER and moving to Golgi.

Clatherin: Involved with vesicles budding off of the Golgi to the plasma membrane and involved with endocytosis through the plasma membrane.

Question 133

What is an SRP made up of?

Answer 133

RNA backbone

6-proteins

Question 134

What are Type I and Type II transmembrane proteins?

Answer 134

Type I: Amino terminal inside lumen, Carboxy terminal outside.

Type II: Carboxy terminal inside lumen, Amino terminal outside

Question 135

What is the purpose of glycosylation of hydrophobic AAs during production?

Answer 135

Transfered to Asn residue

Keeps protein from aggregating prematurely

Signals whether or not the protein is folded properly.

Question 136

How are proteins tagged for the ER?

How is it modulated?

Answer 136

KDEL sequence

Modulated by pH. Lower pH causes carrier protein to bind. Higher pH causes carrier protein to release.

Question 137

Recognize the key clinical features of cholera infection.

Answer 137

Severe acute rapidly fatal watery diarrhea
vomiting
abd pain
dehydration
renal failure
low K+, Ca++
low HCO3-
acidosis
hypoglycemia
coma

Question 138

Describe the role of cholera toxin A and B and the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in
cholera infection.

Answer 138

A: Active
B: Binding

Made by bacteriophage (virus) associated with Cholera bacterium.

Binds to cAMP which turns on CFTR effectively excreting salt and then water.

Question 139

Describe the physiology behind oral rehydration solutions.

Answer 139

Juice/soft drinks. Glucose promoted salt/water uptake.

Question 140

What is the leading cause of morbidity and death with cholera?

Answer 140

Dehydration

Question 141

What bacterial and host molecules contribute to the development of diarrhea with V. cholerae?

Answer 141

Gram-negative motile rod
From brackish water
Acute massive watery diarrhea

Question 142

What molecules are used to distinguish between V. cholerae strains?

Answer 142

OPS - O-specific Polysaccharides

Question 143

Name the molecules that contribute to protection against cholera disease.

Answer 143

Antibodies to OPS.

Question 144

Describe the vaccines available to prevent V. cholerae infections and how they provide protection against disease.

Answer 144

Killed Cholera bug.

B-sub unit

Question 145

How does the CFTR gene protect agains Cholera?

Answer 145

CFTR heterozygosity reduces the Cl- channels in membranes which protects agains the Cholera toxin mechanism.

Question 146

Describe two major routes for small volume endocytosis.

Answer 146

Coated vesicle => early endosome => late endosome => lysosome

Question 147

Explain how quality control of protein synthesis ensured in the ER.

Answer 147

1) It is folded properly
2) If not, it correctly folds using chaperone
3) if not, degraded

Question 148

Describe two types of molecular chaperones.

Answer 148

hsp70: Help fold protein by binding to exposed hydrophobic patches
hsp60: Form large barrel-shaped structures to act as “isolation chambers” to help refold.

Question 149

Describe the proteasome, protein degradation, and the role of ubiquitin.

Answer 149

ATP-dependent protease (1% of cellular protein)

Mediated by ubiquitin (on lysine residue) tagging of proteins (has to have 4 ubiquitins in a row).

Question 150

Describe the functions of the lysosome.

Answer 150

Lysosome degrades all cellular components.

Targeted via the endocytic pathway

Question 151

What is the purpose of degradation?

Answer 151

Misfolded proteins create havoc

Proteins have finite lifetimes

Organelles get damaged - need to be removed

Both good and bad endocytosed materials need to be degraded.

Question 152

Which beta-subunits cleve which AAs?

Answer 152

Beta1: Cleaves after acidic aa
Beta2: Cleaves after basic aa
Beta5: Cleaves after hydrophobic

Question 153

Differentiate between two main types of autophagy: macroautophagy and chaperone‐mediated autophagy.

Answer 153

Macroauthophagy: Series of regulated steps, formation of a double membrane vesicle that engulfs cellular components for degradation.

Chaperone-mediated autophagy: Delivers certain proteins to lysosome in a controlled manner.

Question 154

Describe the process of macroautophagy.

Answer 154

1) Induction (nutrient starvation, growth-factor mediated starvation, exposure to chemo-drugs, Rapamycin, etc.)
2) Vesicle nucleation
3) Vesicle expansion
4) Cargo targeting
5) Vesicle closure
6) Vesicle fusion with endosome
7) Vesicle fusion with lysosome

Question 155

Describe the rationale behind autophagy’s protective action against neurodegeneration.

Answer 155

Degradation of accumulated proteins in neurons.

Question 156

Identify mechanisms by which apoptosis induction and autophagy are connected.

Answer 156

Autophagy might be an induction of apoptosis in certain circumstances.

Question 157

What is autophagy?

Answer 157

Controlled degradation of cellular components.

Question 158

Compare and contrast apoptosis and necrosis in terms of morphology, common triggers of the two phenomena, and
relative importance in physiological and pathological processes.

Answer 158

Necrosis: Cell is starved -> Mitochondria swell -> as ATP production ceases, Na+ pump can’t run -> Cell swells and bursts -> Inflammatory response.

Apoptosis: Nucleus collapses -> hypercondenses -> lysed -> cell loses 1/3 of their volume -> Cell tears itself apart -> phagocytosed before it causes inflammatory response.

Question 159

Name tissues in which there is most and least apoptosis.Suggest reasons for this difference.

Answer 159

Most: Skin, gut (small intestine), immune system

Least: gut (large intestine)

Question 160

Describe the role of caspases in apoptosis, and discuss the role that the mitochondrion may play in the process.Identify the roles of Caspases 8, 9, and 3.

Answer 160

Caspase 8: Signaler of apoptosis (activates Caspase 3)

Caspase 9: Initiator or apoptosis (activates Caspase 3)

Caspase 3: Executioner of the cell

Question 161

Distinguish between the signaling of the intrinsic and extrinsic apoptosis pathways.

Answer 161

Intrinsic: Signalling releases Cyt-C into the cytosol, activating Apaf-1, activating Caspase 9, activating Caspase 3 (The executioner)

Extrinsic: Killer-T cells activate the pathway through ligand-ligand binding. This activates Caspase 8, activating Caspase 3.

Question 162

Discuss the essential biological difference between phagocytosis of apoptotic and necrotic cells.

Answer 162

Apoptotic: cells are recognized by phagocytes (through PS). They are phagocytosed before they burst. No inflammatory response.

Necrotic: cells burst, dumping their contents, triggering inflammatory response.

Question 163

Discuss the importance of apoptosis in tumor formation and progression.

Answer 163

Depressed apoptosis leads to tumor growth.

Question 164

Describe a mechanism by which one cell can induce apoptosis in another cell, and give an example.

Answer 164

Killer T cells have a ligand which engages a ligand on a target cell which activates Caspase 8 which signals Caspase 3 (the executioner).

Question 165

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

aldosterone inhibitors
ibuprofen
heparin
loop diuretics

Answer 165

loop diuretics

diuretics increase excretion, so would decrease K ACE inhibitors and ARB (Retinoblastoma)s, NSAIDS, heparin, and drugs that contain K will increase blood potassium Dietary K also contributes

Question 166

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

Hemangioblastomas
Renal cell carcinomas
Pancreatic cysts
Catecholamine-secreting tumors

Answer 166

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 167

Where does aldosterone act on the kidney?

proximal convoluted tubule
loop of Henle
distal convoluted tubule
collecting duct

Answer 167

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 168

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?

same volume because neither solute can permeate
the cell will be 1/2 its initial volume
the cell will be twice its initial volume

Answer 168

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 169

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

a history of hypertension
kidney failure
neuropathy
immunodeficiency

Answer 169

kidney failure

kidney failure because normally the kidney would excrete excess K

Question 170

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

env
pol
gag
myc

Answer 170

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 171

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

insulin deficiency
insulin resistance
beta agonists
beta blockers

Answer 171

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 172

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

Hemangiosarcomas
Hif1alpha
VEGF-Receptor and PDGF-Receptor
VHL protein complexes

Answer 172

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 173

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

1
300
150
900

Answer 173

150

150 If you remove all the ions from a 1L of plasma, you will have 900mL of water left over = 1:150 ratio

Question 174

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

50%
30%
70%
60%

Answer 174

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 175

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?

It is a strong acid
It is a strong base
It is a weak acid
It is a weak base

Answer 175

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 176

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?

calcium and bicarbonate
insulin and glucose
k-exylate and dialysis

Answer 176

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 177

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

to avoid osmotic diuresis
insulin has a very short half-life
to avoid rapid cellular fluid uptake
to avoid overcorrecting and causing an alkalosis

Answer 177

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 178

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

a 3 year old new onset female who was treated with insulin during the first hour of fluid therapy
a 12 year old new onset male who was given bicarbonate during treatment
a 4 year old new onset female who showed a less than normal increase in sodium levels during treatment
a 10 year old diabetic diagnosed 5 years ago

Answer 178

a 10 year old diabetic diagnosed 5 years ago

established diabetics have less risk of cerebral edema than new onset. Administration of bicarbonate, insulin during first hour, and smaller than normal increase in Na are all risk factors for cerebral edema. Also, increased volume of fluid treatment increases risk.

Question 179

Which of the following substances will not dissociate in a solution?
  NaCl 
  (NH2)2CO 
  CaCl2 
  K2SO4

Answer 179

(NH2)2CO

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

Question 180

Which of the following is a characteristic of SNARE proteins?

vesicles are carried to the fusion site via microtubule and actin tracts
they are insoluble NSF attachment protein receptors
there are five main classes of SNARE proteins
SNAPS and syntaxins are located on the target membrane

Answer 180

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 181

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?

same as initial volume because the solution is isotonic
the cell will be 1/2 its initial volume
the cell will be twice its initial volume
the cell will swell and lyse

Answer 181

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 182

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

hepatic encephalopathy due to increased renal ammonia production
impaired muscle contraction leading to paralysis
increased BP over time due to vasoconstriction
cardiac arrhythmias

Answer 182

cardiac arrhythmias

arrhythmias are the most serious symptom. Presenting symptoms = low BP, high HR, decreased appetite, diarrhea, low K Replete and 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 183

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

Elevated potassium is toxic to kidneys
Myoglobin is toxic to kidneys
The patient is likely alkalemic with a blood pH >7.45
Glomerular filtration is elevated

Answer 183

Myoglobin is toxic to kidneys

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

Question 184

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?

2%
10%
20%
30%

Answer 184

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 185

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?

total osmolarity = 200, Na = 200, Cl = 0
total osmolarity = 400, Na = 100, Cl = 100
total osmolarity = 400, Na = 200, Cl =0
total osmolarity = 200, Na = 100, Cl =100

Answer 185

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 186

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?

net uptake of amino acids will stop
amino acids will continue entering the cell at the same rate
the pump will increase its transport capacity
the pump will switch directions

Answer 186

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 187

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?

Ca and H2O
Cl and H2O
Urea and H2O
Bicarbonate and H+

Answer 187

Urea and H2O

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

Question 188

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?

Sec1
alphaSNAP
VAMP
molecular motor protein

Answer 188

Sec1

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

Question 189

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

Cells are less acidic intracellularly than extracellularly
Venous blood is more acidic than arterial blood
Normal body [H+] is 24nmol/L
The kidneys and the liver are the primary regulators of the body’s pH

Answer 189

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 190

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

the reflection coefficient of glucose is greater than the reflection coefficient of NaCl.
an isotonic solution exists until glucose is able to enter the cell
a hypertonic solution exists until glucose is able to enter the cell
a hypertonic solution is created when glucose enters the cell

Answer 190

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 191

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?

Renal cell carcinoma
Hemangioma
Pancreatic cysts
Angiomatosis retinae

Answer 191

Pancreatic cysts

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

Question 192

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

activates RB (Retinoblastoma) and p53
activates RB (Retinoblastoma)
inhibits p53
inhibits p53 and RB (Retinoblastoma)

Answer 192

inhibits p53 and RB (Retinoblastoma)

oncogenic viruses inhibit RB (Retinoblastoma) and p53

Question 193

What is the inheritance pattern for von-Hippel Lindau?

Autosomal recessive
Autosomal dominant
X-linked recessive
X-linked dominant

Answer 193

Autosomal dominant

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

Question 194

p53 mutations are most often:

frameshift
missense
splicing errors
nonsense

Answer 194

missense

p53 mutations are mostly missense (75%)

Question 195

Which of the following is an expected result of a drug that enhances the action of normal p53?

Increased cell division
Increased progression from S phase to M phase
Increased apoptosis in damaged cells
Decreased DNA repair

Answer 195

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 196

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?

6. 6
7. 3
8. 5
9. 8

Answer 196

7. 3

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

Question 197

Which of the following correctly describes the function of NSF?

cleavage of SNARE complexes and inhibits neurotransmitter release
hydrolysis of ATP to disassemble the SNARE complex
maintains efficacy of the SNARE complex
execution of the ‘zippering’ phase of membrane fusion

Answer 197

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 198

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?

it will shrink
it will swell quickly
it will swell eventually
it will not change size

Answer 198

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. So at first, the ECF osmotic force = .5(600) = 300, and it will be isotonic. However, the solute will move into the cell and water will follow it. The cell will eventually swell and lyse.

Question 199

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

regulation of beta catenin localization to the nucleus
regulation of DNA repair following UV damage
degradation of free Beta-catenin in the cytoplasm
synthesis of beta catenin following DNA damage

Answer 199

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 200

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

If O2 levels increase, Hif1 alpha will induce hypoxia
If O2 level decrease, Hif1 alpha will not be ubiquitinated and will promote vascularization.
Hif 1 alpha prevents O2 levels from increasing
In hypoxic cells, Hif 1alpha acts independently of Hif1 beta.

Answer 200

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.

Question 201

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

33%
50%
66%
70%

Answer 201

66%

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 202

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?

increased leukocytes
increased K+
decreased K+
increased HCO3-

Answer 202

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 203

A transporter in the proximal convoluted tubule of the kidney expels a bicarbonate 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?

primary active transporter
ion channel
co-transporter
exchanger

Answer 203

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 204

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

13 L inside of cells, 27 L outside of cells
18 L inside of cells, 27 L outside of cells
27 L inside of cells, 13 L outside of cells
27 L inside of cells, 18 L outside of cells

Answer 204

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 205

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?

the cell to continue to divide
the cell will stop dividing
CDK will phosphorylate RB to turn it off
CDK will phosphorylate RB to turn it on

Answer 205

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 206

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

loss of heterozygosity is associated with Familial Adenomatous Polyposis
heterozygosity follows an autosomal recessive inheritance pattern
it is an oncogene
all of the above

Answer 206

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 207

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

Simultaneously before birth
Simultaneously just before onset of the individual’s symptoms
Separately, once in the germline and once over the lifetime of the individual
Separately, once after conception and once just before birth

Answer 207

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 208

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

tumor suppression
oncogene activation
transcription factor localization to the nucleus
DNA repair

Answer 208

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 209

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

Increased cell division
Increased progression from S phase to M phase
Increased apoptosis in damaged cells
Decreased DNA repair

Answer 209

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 210

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

infect cells and induce growth
encode DNA repair factors
are oncogenes
cause splicing errors that spur proliferation

Answer 210

encode DNA repair factors

p53, BRCA1 and BRCA2 encode DNA repair factors

Question 211

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?

discovery of a retinoblastoma in her left eye
a positive family history of retinoblastomas
both copies of RB (Retinoblastoma) are inactivated in tumor cells
only one copy of RB (Retinoblastoma) is inactivated in tumor cells

Answer 211

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 212

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

autosomal recessive disorder with a dominant inheritance pattern
autosomal recessive disorder with a recessive inheritance pattern
autosomal dominant disorder with a recessive inheritance pattern
autosomal dominant disorder with a dominant inheritance pattern

Answer 212

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 213

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?

negative
positive
neutral
amphipathic

Answer 213

negative

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

Question 214

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

increased lipolysis and gluconeogenesis in the liver
enhances ketone body formation
increased storage of glycogen in the liver
decreased fatty acid storage

Answer 214

increased storage of glycogen in the liver

insulin increases caRB (Retinoblastoma)ohydrate storage as glycogen in the liver Results of insulin release: Decreases lipolysis and gluconeogenesis (liver) Inhibits ketone body formation Increases FA storage as triglycerides Signals cellular uptake of glucose

Question 215

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?

H is at equilibrium
H is being pumped into the cell
H is being pumped out of the cell
There is a net leak of H out of the cell

Answer 215

H is being pumped out of the cell

H is pumped out. Vm = -80 mV E = 60log (50/100) = -18 mV

Question 216

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

a helical domain
a transmembrane domain
vesicular transport
located in target membrane

Answer 216

a helical domain

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

Question 217

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

the cell will be arrested in G1 phase
the cell will be arrested in S phase
the cell will be able to divide
the cell will no longer have a mitotic checkpoint

Answer 217

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 218

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?

pKa= log ([H+][A-]/[HA])
pH= pKa + log ([acid]/[base])
pH= pKa- log ([base]/[acid])
pH= pKa+log ([base]/[acid])

Answer 218

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 219

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?

Her great aunt had Li Fraumeni Syndrome
Her two younger siblings were both still births
Her 40-year-old sister and her 20-year-old daughter both have ovarian cancer
Her mother, her aunt, and her grandmother were all diagnosed with breast adenocarcinoma before the age of 60

Answer 219

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 220

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

3osM
35osM
70 osM
105 osM

Answer 220

70 osM

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

Question 221

95% of p53 mutations alter p53 function by:

increasing binding of p53 at its DNA domain
increasing binding of p53 at it transactivation domain
inhibiting the DNA binding domain
inhibiting the transactivation domain

Answer 221

inhibiting the DNA binding domain

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

Question 222

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

fewer cells will proceed into S phase
fewer cells will proceed into G1 phase
more cells will be arrested in G1 phase
more cells will proceed into S phase

Answer 222

more cells will proceed into S phase

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

Question 223

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?
Na is at equilibrium
Na is being pumped into the cell
Na is being pumped out of the cell
There is a net leak of Na out of the cell

Answer 223

Na is being pumped out of the cell

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

Question 224

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

the solution is isotonic
the solution is hypertonic
the solution is hypotonic
the cell has an ion pump

Answer 224

the solution is hypertonic

Question 225

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?

[Na+]i [K+]o; [Cl-]i ECF; K+=ICF>ECF; Cl-=ICF ECF; K+=ICF>ECF; Cl-=ICF>ECF
Na+= ICFECF; Cl-=ICF>ECF

Answer 225

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

Question 226

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

unresponsive to growth control mechanisms
immortality
metastatic
undifferentiated

Answer 226

metastatic

benign tumors are not invasive or metastatic but they are: undifferentiated unresponsive to growth control signals immortalized

Question 227

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

Insig binds SCAP only when cholesterol is low
Insig binds SCAP only when cholesterol is high
Insig binds to SREBP only when cholesterol is low
Insig binds to SREBP only when cholesterol is high

Answer 227

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 228

Which is a major function of the Golgi?

Early post translational modifications
Control of cholesterol homeostasis
Proteolytic processing
Synthesis of proteins on membrane bound ribosomes

Answer 228

Proteolytic processing

The functions of the golgi complex are

Synthesis of complex sphingolipids from the ceramide backbone

Additional post-translational modifications of proteins and lipids

Proteolytic processing

Sorting of proteins and lipids for post-golgi comprtments

The rest of the answer choices are true of the function of the ER.

Question 229

E. coli bacteria induces diarrhea by making an enzyme that affects the extrinsic pathway of apoptosis, what is the function of this enzyme?

It oxidizes CD95 and makes it unable to transduce the cell’s signal.
It is a bacterial FLIP that binds to caspase 8 and makes in inactive.
It mimics Fas and prevents the Fas ligand from binding.
It glycosylates FADD and makes in unable to activate caspase 8.

Answer 229

It glycosylates FADD and makes in unable to activate caspase 8.

Question 230

At the peak of an action potential Vm is:

zero
equal to Ek
positive
negative

Answer 230

positive

positive (approaches ENa)

Question 231

Which of the following people is at most risk for developing multiple sclerosis (MS)?

A male between 60-75 years
A female between 60-75 years
A male between 16-45 years
A female between 16-45 years

Answer 231

A female between 16-45 years

A female between 16-45 80% of patients have onset between 16-45 Females have 2.4 to 1 risk ratio. Exposures and risks are determined during first 15 years of life

Question 232

Myelin is important for neuron function because it:

Increases capacitance
Decreases resistance
Decreases surface area
Decreases conduction velocity

Answer 232

Decreases resistance

Myelin decreases capacitance so there is less charge that is need to produce an AP Myelin increases surface area so that the resistance decreases and the conduction velocity therefore increases.

Question 233

Which of the following is true regarding antibiotic treatment of cholera:

They are effective in the treatment of minor cases of cholera
They can shorten the duration of disease
They increase risk of further infectivity
They are recommended as standard treatment of cholera

Answer 233

They can shorten the duration of disease

Antibiotics can shorten the duration of the disease, but should only be used in severe cases. Antibiotics are not the standard of care (delivery of fluids or oral dehydration therapy is standard). However, when used they will decrease the risk of further infectivity.

Question 234

Which of the following is a true statement regarding ion channels?

Their gating is controlled only by extracellular chemicals
Ion channels are seen in the plasma membrane and the membrane of intracellular organelles
All ion channels respond to one stimulus
All of the above are true statements
Mutations of ion channels are responsible for diverse human diseases

Answer 234

Ion channels are seen in the plasma membrane and the membrane of intracellular organelles

Ion channels are present in plasma membranes and in the membranes of intracellular organelles.

Their gating is controlled by a vast array of stimuli.

Some channels respond to multiple stimuli

Ion channels are essential for function of diverse cell types, including muscle, neurons, T lymphocytes and pancreatic B cells.

Ion channels are important targets of natural products for predation and also therapeutic targets.

Question 235

Directionality of protein transport is determined by:

the presence of GTP
location of GTPases
RAN-GTP
the RAN cycle

Answer 235

the RAN cycle

the RAN cycle determines protein directionality. Enzyme location determines RAN’s GTP bound or unbound state (RanGAP at the cytoplasmic face of the NPC, the exchange factor RCC1 in the nucleus) RAN-GTP is high in the nucleus, low in the cytosol mRNA transport doesn’t use RAN (energy consumed by Dbp5, an ATP-dependent RNA helicase tethered to cytoplasmic face of NPC) rRNA transport uses both GTP (Ran) and ATP (Dsb5).

Question 236

A seven year old female patient presents to your clinic with elevated k levels and a venous pH of 7.01. What other symptoms are to be expected in this patient?

a fever
moist mucous membranes
nausea, decreased appetite, weight loss
lack of urination

Answer 236

nausea, decreased appetite, weight loss

DKA patients are not typically febrile Dry mucosa, cracked lips, sunken eyes/cheeks Weight loss, decreased appetite, vomiting, somnolence Polyuria, polydipsia (diabetes) Delayed capillary refill Fruity breath Increased/rapid respiration ‘Kussmaul’ respirations (trying to excrete CO2)

Question 237

Order the following steps of macroautophagy correctly.

I. Regulation of protein conjugation events to extend into membrane

II. Activate a PI3K complex

III. Fuse with lysosome

IV. Nucleation of membrane forms autophagosome

II, I, IV, III
II, III, IV, I
II, I, III, IV
II, III, I IV

Answer 237

II, I, IV, III

The process of macroautophagy is:

Activate a PI3K complex that allows nucleation of a membrane that will eventually form the autophagosome.
Regulation of protein conjugation events to extend membrane.
Randomly capture or specifically deliver cargo to the extending autophagosome, then join the membrane to close the vesicle
Fuse with lysosome
Recycle amino acids and other macromolecular precursors.

Question 238

Neurodegenerative diseases such as Alzheimer’s that result from the accumulation of plaques within the nucleus might be caused by:

a decreased ability of the NPCs to exclude molecules from nuclear entry as you age
decreased NPC dilation as you age
an increased presence of importin alpha inside the nucleus
localization of transcription factors away from the nuclear envelope

Answer 238

a decreased ability of the NPCs to exclude molecules from nuclear entry as you age

As you age, NPCs lose their ability to effectively exclude molecules from the nucleus which results in the accumulation of plaques inside the nucleus

Question 239

Increasing resistance (R) of the membrane will have which of the following effects?

increase conduction velocity of an axon
decrease speed of electric current
decrease change in Vm over distance
slow action potential conduction velocity

Answer 239

increase conduction velocity of an axon

increasing membrane resistance will keep more of the current inside the axon. Less will leak out and the AP will be stronger and faster than it would be with a lower membrane resistance (this is one of the functions of myelin)

Question 240

Which of the following components of nucleoporin structure is highly conserved between species?

the number of cytoplasmic and nuclear filaments
three-dimensional architecture
the amount of FG repeats per nucleoporin
the number of nucleoporins per cell

Answer 240

three-dimensional architecture

3D structure of nucleoporins is highly conserved. 30% of nups contain FG repeats Nups = nucleoporins, 30 distinct proteins repetitively arranged 8 filaments outside (cytoplasmic), 8 filaments inside that form nuclear basket F compartments repel each other so proteins are natively unfolded without secondary structure or a hydrophobic core (tails to not end up in an aggregated shape)

Question 241

An MRI on a patient shows lesions consistent with MS. You test the patient’s visual pathway using a Visually Evoked Potential, and notice a decrease in amplitude but not a delay in response. What is the most likely conclusion you can make at this time?

The patient does not have MS
The patient has some demyelination
The patient has lost some neuronal axons
This is an autoimmune response

Answer 241

The patient has lost some neuronal axons

Decreased amplitude = loss of axons Decreased speed = demyelination Without additional studies and time, one cannot definitively conclude that this is or is not MS, or that this is autoimmunity This finding is still consistent with MS, later tests will show progression of a longer latent period and decreased amplitude

Question 242

Channel selectivity of Ion channels can be based on which of the following?

  Charge 
  Size 
  Dehydration 
  Multiple Binding Sites
  All of the Above

Answer 242

All of the Above

Selectivity of channels varies. Some channels are highly selective and some are moderately selective. The charge is very important, cation/anion. Also the valence can matter.

Ion size, dehydration and multiple binding sites can also affect selectivity of an ion channel.

Question 243

Where in the cell can a high concentration of RAN-GTP be found?

nucleus
cytosol
ER
Golgi

Answer 243

nucleus

nucleus because this is where it acts by disassembling cargo molecules from their cargo receptors, or acting as an allosteric modifier for export receptors.

Question 244

Which of the following is paired correctly regarding coat structures and their function?

COPII: ER to Golgi: forward
COPI: Golgi to plasma membrane
Clathrin: Golgi to ER: backward
All of the above are correct

Answer 244

COPII: ER to Golgi: forward

COPII: ER to golgi: forward

COPI: golgi to ER: backward

Clathrin: golgi to plasma membrane

Question 245

Which is not a main type of autophagy?

Macroautophagy
Microautophagy
Protease-mediated autophagy
Chaperone-mediated autophagy

Answer 245

Protease-mediated autophagy

Question 246

What is the function of K+ channel blockers as a treatment for MS?
K+ channel blockades stop the progression of demyelination
K+ channel blockades enhance AP conduction by preventing rapid repolarization via K+ efflux
K+ channel blockades can prevent calcium-mediated nerve injury
K+ channel blockades can prevent seizures in MS patients

Answer 246

K+ channel blockades enhance AP conduction by preventing rapid repolarization via K+ efflux

K+ channel blockers prolong action potentials by inhibiting K+ channels that normally allow rapid K+ efflux during repolarization. They do not stop the progression of disease, they just help people walk better (delfampridine) Seizures are a common side effect because AP’s in the brain are also prolonged.

Question 247

Major functions of the ER are:

Co-translational folding of proteins
Synthesis of complex sphingolipids from the ceramide backbone
Adding post-translational modification of proteins and lipids
There are multiple compartments, stacked like pancakes with cis and trans end

Answer 247

Co-translational folding of proteins

The functions of the ER are:

Synthesis of lipids (phospholipids, ceramide, cholesterol—mainly in sER)

Control of cholesterol homeostasis (cholesterol sensor and synthesis)

Storage of Ca2+ (rapid uptake and release)

Synthesis of proteins on membrane bound ribosomes (rough ER)

Co-translational folding of proteins and early post translational modifications

Quality control

The other answer choices are functions of the golgi complex

Question 248

Which of the following is a defining feature of apoptosis?

Collapsed nucleus
Burst of cell membrane
Organelles leaving the cell through exocytosis
All of the Above

Answer 248

Collapsed nucleus

Collapsed nucleus is the defining morphological feature of apoptosis

Question 249

A patient presents to your clinic requesting medication preparations for cholera. The patient is planning a 2 week mission trip to Haiti where there has been a major cholera outbreak. He has already received ORT supplies for his trip. He will be staying in a small village where he will be preparing meals for the local people as well as volunteers from the Red Cross, and is departing in four days. His family has been doing mission work for many years, and both of his parents have had a history of cholera from when they were living in Bangladesh during the early 1990’s. Besides ORT, what do you recommend to this patient?

Cholera vaccine
Antibiotics to take as a precaution
Anti-diarrheals to pack in his suitcase
Nothing

Answer 249

Nothing

Nothing The cholera vaccine is not licensed in the US, and is only effective after the second dose, and doses must be given one week apart. Only recommended for long durations of stay in a place where cholera is endemic (he is only going for 2 weeks) Antibiotics are only used for severe cases Antidiarrheals are never recommended He already has ORT so you don’t need to give him anything Advise on sanitation, handwashing, and careful water and food choices

Question 250

A Kv and Nav structured ion channel has a unique way of “voltage-sensing”, how is this accomplished?

S6 helices
S6 B-pleated sheets
S4 helices
S4 B-pleated sheets

Answer 250

S4 helices

Voltage sensing is accomplished by S4 helices, the helices contain a positively charged Arg or Lys every 3rd position and translocate in response to changes of the S4 helices cause opening of the activation gate.

Question 251

Which of the following is correct regarding the Na/K/Cl exchanger of epithelial cell membranes?

always is located in the apical membrane
drives the uptake of Cl into the cell that results in NaCl secretion
relies directly on ATP
causes concentration of Cl inside the cell to be low

Answer 251

drives the uptake of Cl into the cell that results in NaCl secretion

the Na/K/Cl exchanger is located on the Basolateral membrane It relies on energy from Na leakage to uptake Cl (causes high Cl concentrations) Eventually Cl leaks out into the lumen (apical side) and drags Na and water with it = secretion

Question 252

After the cholera toxin binds to the GM1 receptor on the cell’s membrane, what happens next?

The A subunit is cleaved, endocytosed, and cGMP is produced
The B subunit is cleaved, endocytosed, and cGMP is produced
The A subunit is cleaved, endocytosed, and cAMP is produced
The B subunit is cleaved, endocytosed, and cAMP is produced

Answer 252

The A subunit is cleaved, endocytosed, and cAMP is produced

There are two subunits to the cholera toxin: A and B. The A is the active site while B is the transport molecule. The whole toxin binds to the GM1 receptor, but only A is cleaved and endocytosed. This in turn activates adenylyl cyclase which produces cAMP. This leads to activation of CFTR which leads to efflux of chloride ions.

Question 253

Which of the following transporters is located on the apical membrane and is the cause of the ionic efflux that leads to severe diarrhea:

Na/K pump
CFTR channel
K channels
Na/K/Cl cotransporter

Answer 253

CFTR channel

CFTR is a chloride channel on the apical side (affected by cholera and CF). The massive efflux of chloride ions causes water to follow and produces diarrhea.

Question 254

Autophagy is induced during times of?

ischemia
Necrosis
Oxidative Stress
Nutrient Stress

Answer 254

Nutrient Stress

Question 255

Alpha adrenergic receptor activation triggers peripheral vasoconstriction via which of the following second messengers?

IP3 and DAG
cAMP
beta receptors
muscarinic receptors

Answer 255

IP3 and DAG

alpha adrenergic receptors trigger peripheral vasoconstriction of smooth muscle that increases BP at the lungs, heart and skeletal muscle. IP3 and DAG 2nd messengers - Ca into cytosol - smooth muscle contraction ACE-inhibitors decrease BP by inhibiting peripheral vasoconstriction.

Question 256

What role to B-cells play in MS?

They are always anti-inflammatory
They activate effector T-cells
They inactivate Th2
They release IL10 cytokines

Answer 256

They activate effector T-cells

They activate effector T-cells This is why targeting and depleting specific B-cells is an effective therapy in MS

Question 257

Which describes the action of Hsp60?

Hsp60 acts by forming an elaborate barrel shaped structure that acts as an isolation chamber to help refold the misfolded protein
Hsp60 acts by binding to an exposed hydrophobic patch in an incompletely folded protein and prevents aggregation.
Hsp60 acts taking up misfolded proteins by endocytosis and degrading them.
Hsp60 acts by attaching a string of amino acids to tag a protein that is misfolded for degradation by a proteasome.

Answer 257

Hsp60 acts by forming an elaborate barrel shaped structure that acts as an isolation chamber to help refold the misfolded protein

B describe Hsp70, C describes the actions of lysosome, but instead of taking up misfolded proteins, lysosomes take up extracellular or intracellular material. D partially described Ubiquitin, which tags proteins for degradation by proteasome after being tagged by a chain of ubiquitin called “polyubiquitin”.

Question 258

Binding of an agonist to a G-protein coupled receptor at its transmembrane domain causes a conformational change that results in which of the following functions?

activates the receptor and triggers signal transduction to begin
inhibits signal transduction
triggers rapid degradation of beta and gamma subunits
binds alpha proteins to each other

Answer 258

activates the receptor and triggers signal transduction to begin

agonists activate GPCR’s and cause a conformational change that begins signal transduction. On the G alpha subunit GDP - GTP by a GEF GTP on G-alpha subunit allows it to go to effectors (enzymes that make 2nd messengers or ion channels that control perm) An intrinsic GTPase returns the GPCR back to its inactive state by hydrolyzing GTP to GDP.

Question 259

What is the maximum concentration of urine solutes?

600 mosM
700 mosM
900 mosM
1200 mosM

Answer 259

1200 mosM

Question 260

Caffeine acts by:

activating phosphodiesterases
inhibiting phosphodiesterases
inhibiting GTP
triggering hyperpolarization

Answer 260

inhibiting phosphodiesterases

caffeine inhibits phosphodiesterases (that hydrolyze cAMP to AMP which turns off PKA) Increases PKA levels

Question 261

Discuss the concept of a cytoskeleton.

Answer 261

The network of protein filaments which give the cell mobility, structure and mechanical transport.

Question 262

Explain the concept of molecular motor.Explain the mechanisms oftubulin‐based movement and intracellular transport.

Answer 262

Kinesins -> walk toward (+) end of microtubule
Dynein -> walk toward (-) end of microtubule

Both molecules transport molecules and cargo vesicles using ATP hydrolysis.

Question 263

Discuss the role of microtubules in mitosis.

Answer 263

1) attach to chromatin
2) stabilize on cell wall
3) overlap and pull chromosomes apart
4) overlap and indicate where contractile ring should form

Question 264

Discuss cytoskeletal dynamics and the role of certain proteins in actin filament formation, polymerization/ depolymerization.

Answer 264

FH2: Grows actin in bundles (straight lines) by binding two actin molecules and adding them to chain.

ARP2/3: Grows actin in branches by binding one actin molecule and adding them to the side of an existing chain.

Question 265

Describe the role of actin cytoskeleton in epithelial cell polarity and discuss some diseases associated with that.

Answer 265

Actin grows toward apical membrane increasing surface area to allow for proper absorption of nutrients. Lack of epithelial polarity is fatal.

Question 266

Explain the concept of molecular motion, and the mechanism of actin‐based organelle movement and muscle contraction.

Answer 266

Molecular motion and actin-based organelle movement is accomplished through ATP hydrolysis (not GTP).

Question 267

Discuss the concept and the key steps of cell movement.

Answer 267

1) ARP2/3 complex regulates lamellipodia formation
2) Lamellipodium extends
3) Focal contacts form
4) Backside contracts, releasing tension

Question 268

Describe the role of actomyosin ring in cell division.

Answer 268

Actomyosin ring pinches off membrane to separate both cellular compartments

Question 269

Describe the mechanisms regulating the establishment and activation of the actomyosin ring and identify examples of asymmetric cell division.

Answer 269

Regulation of actomyosin ring by ECT2 (overlapping microtubules) -> Rho-GTP -> contractile ring

Question 270

Describe principle types of detectors of extracellular signaling molecules.

Answer 270

Ligand-gated ion channels
GPCRs
Enzyme-linked receptors
Nuclear receptors

Question 271

List other “tools” of signaling pathways, including at least three 2nd messengers.

Answer 271

2nd messengers: Ca++, cAMP, IP3, DAG, NO

Other tools:

• Protein modification (phosphorylation, acetylation, glycosylation, ubiquinylation, proteolytic cleavage).
• Protein-protein binding
• GTP/GDP exchange

Question 272

Describe at least three mechanisms for signal termination (including phosphodiesterases).

Answer 272

Extracellular termination molecule
Receptor desensitization
2nd messenger
Phosphorylation
Dephosphorylation
Protein binding/targeting

Question 273

Describe mechanism of receptor tyrosine kinase (RTK) activation.

Answer 273

1) Ligand binds
2) RTK dimerized
3) Self-phosphorylation
4) Activation

Question 274

How are Ras proteins regulated?

Answer 274

GTPase Activating Proteins (GAP): Turn off Ras by hydrolizing GTP to GDP

GNP Exchange Factors (GEF): Turn on Ras by removing GDP from Ras to allow GTP to bind

Question 275

Describe mechanism of action of two main classes of RTK‐targeted anti‐cancer agents(antibodies and TKI’s).

Answer 275

Anitbodies: (cetuximab) blocks the ligand binding site.

TKIs: (gefitinib) blocks kinase activity by binding to ATP pocket

Question 276

Describe mechanism of resistance to TKI’s such as EGFR inhibitors.

Answer 276

Secondary mutations

Other signaling pathways

Question 277

Describe microtubule properties functional roles, and protein composition

Answer 277

Roles: cellular cytoskeleton; intracellular transport; cell division; cilia

Protein composition: Alpha- and Beta-tubulin protofilaments which form barrel like structures.

Question 278

Describe intermediate filament properties functional roles, and protein composition

Answer 278

Roles: mechanical stability

Protein composition: alpha-helical filament (specific to function), forms coiled coils, forms staggered tetramer or two cc dimers, forms tetramers packed together.

Question 279

What do microtubule capping proteins and severing proteins do?

Answer 279

Capping proteins add GTP cap to plus end of microtubules, stabilizing them

Severing proteins remove GTP cap from plus end, allowing tubule to fray. Karatanin; Spastin; Fidgetin

Question 280

Describe micro filament properties functional roles, and protein composition

Answer 280

Roles: Cell movement, contraction

Protein composition: Actin helical filament

Question 281

Explain molecular mechanism of stimulation of ras GTPase by RTKs.

Answer 281

Grb is an adaptor protein that consists of SH2 and SH3 domains.
SH2 bind to Phospho-Tyr peptides
SH3 bind to Pro-peptides binds to Sos - bringing it close to Ras which activates it.

Question 282

Identify the basic structural characteristics of GPCRs that mediate ligand binding and coupling to G proteins.

Answer 282

7-transmembrane domains (N-out, C-in)

Recognition site inside alpha-helical barrel on extracellular side.

Question 283

Explain how G protein-coupled receptors activate hetero-trimeric G proteins and diagram the GTP-hydrolysis cycle of G protein signaling.

Answer 283

Ligand binds GPCR
GDP is released from G-alpha
G-alpha binds to GTP activating it
G-alpha dissociates from G-beta and G-gamma
G-alpha hydrolizes GTP->GDP inactivating it
G-alpha rebinds to G-beta and G-gamma

Question 284

Describe the function of second messengers in receptor signaling and give two examples for how they are generated by activated G proteins.

Answer 284

Secondary messengers propagate the signal from the GPCR to downstream effectors
ATP->cAMP
PLC cleaves IP3 from lipid membrane

Question 285

Explain how receptor activation leads to signal termination through receptor desensitization and coupling to additional pathways.

Answer 285

Receptor activation can bind to GPCRs to inactivate them or desensitize them. It can also activate degradation of secondary messengers (e.g. phosphodiesterases cAMP->AMP)

GRK kinase can bind to p-loops and prevent subunits from binding. Recruits beta-arrestin which leads to internalization removing ligand binding pocket from extracellular space.

Question 286

Give two examples of drugs that act through modulating different steps in a receptor-G protein-second messenger signaling cascade.

Answer 286

m2-muscarinic cholinergic receptor signaling by K+ channel activation in heart (decreases excitability)

b-adrenergic receptor signaling through Gs and cAMP production in the lung (smooth muscle dilation)

m3-muscarinic cholinergic receptor signaling through PLC activation in lung (bronchoconstriction)

Question 287

Describe the Cellular Signal Transduction pathway

Answer 287

1) Extracellular signal (ligand)
2) Transmembrane receptor
3) Intracellular signal transducers
4) Modulation of channels and enzyme effectors
5) Production of diffusible secondary messengers
6) Regulation of target protein phosphorylation
7) Specific cellular response

Question 288

Describe a phosphorylation reaction (including which amino acids can be phosphorylated) and explain how it can affect a phosphorylated protein.

Answer 288

Nucleophilic attack of hydroxyl group of Threonine, Serine or Tyrosine on gamma-phosphate of ATP.

Threonine/Serine Tyrosine

Question 289

List at least two other types of secondary protein modification

Answer 289

Acetylation
Ubiquination
Methylation

Question 290

Explain the structure of an ATP molecule.

Answer 290

Adenosine

3 Inorganic phosphates

Question 291

Explain how protein kinases can be classified and describe examples.

Answer 291

Based on the amino acid they phosphorylate
their substrate,
their activation, or
their phylogenetic relationship

Question 292

Describe the structure/function of a protein kinase and principles of their regulation (including requirement for activation loop phosphorylation in some but not all kinases).

Answer 292

Small and large lobe
ATP binds in the cleft between the two
Large lobe interacts with substrate
Closed conformation moves ATP into phosphorylation position
Open conformation allows exchange of ADP for ATP

Question 293

Describe the functions of cytoplasmic Ca2+ ion buffers and how these buffers affect cytoplasmic Ca2+ signals.

Answer 293

Allows Ca++ to be locally concentrated
Can act as a calcium sink
Allows high concentration in ER/SR without a large concentration gradient

Question 294

Describe the routes by which extracellular Ca2+ enters the cytoplasm, the routes by which Ca2+ moves out of the ER/SR into the cytoplasm, and the routes by which Ca2+ is extruded from the cytoplasm (a) into the extracellular space and (b) into the lumen of the ER/SR.

Answer 294

Ca++ from ECF

• Voltage gated Ca++ channels (depolarization)
• Ligand gated Ca++ channels (nAch/Glutamate)
• Store-operated Ca++ channels

Ca++ from ER/SR

• RyR
• IP3

Ca++ to ECF

• PMCa ATPase
• Na+: Ca++ transporter

Ca++ to ER/SR
- SERCa ATPase

Question 295

Describe EF hands and C2 domains, identify the archetypical protein that contains EF hands and the archetypical protein that contains a C2 domain, and determine whether these domains are present in other proteins.

Answer 295

EF hands (Calmodulin) - in all plants and animals

C2 domains in PKC

Question 296

Explain the basics of stem cells, their niches, and the commitment (differentiation) of stem cells into different lineages.

Answer 296

Step cells are pleuripotent

In adults, it gets indicated into a niche depending on surrounding environment (basement membrane, other cells etc).

Question 297

Explain the concept of adult stem cell plasticity.

Answer 297

Given the right inputs, adult stem cells can undifferentiate and be used to generate new tissues

Question 298

Explain the concept of reprogramming adult somatic cells into induced pluripotent stem (iPS) cells or embryonic-like stem cells.

Answer 298

Adult somatic cells can be programed back into stem cells in order to grow new tissue to repair environmental damage.

Question 299

Describe the role of stem cells in the initiation and maintenance of cancer.

Answer 299

Epithelial stem cells are present throughout life making them strong targets for carcinogenic activity. They already have the ability to divide. The just need the ability to dissociate and spread.

Question 300

Identify the sources of androgen in the body relevant to prostate cancer.

Answer 300

Testis - 90-95%
Adrenal Glands: 5-10%
Cancer cells themsevles

Question 301

Describe the structure androgen receptor in prostate cancer.

Answer 301

4 Structural Domains

• N-terminus transactivation domain (NTD)
• DNA binding domain (DBD)
• Hinge region
• C-terminus ligand binding domain (LBD)

Question 302

Describe the mechanisms of resistance to traditional endocrine therapy for prostate cancer.

Answer 302

AR activation via non-gonadal testosterone (Adrenals)
Over expression of AR
AR mutation - permiscous activation
Truncated AR - constitutive activation of LBD

Question 303

Describe the function of the androgen receptor in prostate cancer.

Answer 303

• Resides in cytoplasm
• Upon ligand (testosterone) binding, inhibitory chaperones dissociate allowing AP to enter nucleus
• AR homodimerizes and binds to AR elements on DNA
• AR recruits co-activators for gene expression

Question 304

Describing enzalutamide and abiraterone’s effect on endocrine therapy resistance.

Answer 304

Cytochrome P (CYP) 17 plays a key role in androgen production
Abiraterone is a specific and potent inhibitor of CYP 17 blocking production from all sources of androgens

Question 305

Discuss the contributions of the ECM to cell and tissue function.

Answer 305

Extracellular matrix is critical in maintaining survival signals for cells, preventing them from apoptotic cell death.

Question 306

Define the four major classes of ECM components and their properties.

Answer 306

Glycosaminoglycans (GAGs)
Fibrous proteins (Collagen/Elastin)
Multidomain adapter proteins (Fibronectin/Laminin)
Water and solutes

Question 307

Define two types of fibrillar proteins and at least two types of multidomain adapter proteins of the ECM.

Answer 307

Fibrillar proteins:

• Collagens are fibrous proteins and the most abundant proteins in mammals
• Elastin provides elasticity, an important property of many tissues (skin, lungs, blood vessels, etc.)

Multidomain adapter proteins:

• Fibronectin is a large, dimeric glycoprotein whose two large subunits are linked together by disulfide bonds.
• Laminin is another very large protein, composed of three subunits (α,β,γ) that form an asymmetric, disulfide-linked cross with the longer arm formed by a helical structure containing long stretches of all three subunits.

Question 308

Discuss the role of MMPs in ECM remodeling.

Answer 308

to come

Question 309

Discuss the role of adhesion in cell function and survival.

Answer 309

to come

Question 310

Define and describe at least three different types of cell adhesion molecules (CAMs) and their ligands.

Answer 310

to come

Question 311

Discuss the role of CAMs in signaling.

Answer 311

to come

Question 312

Describe proteins associated intracellularly with CAMs.

Answer 312

to come

Question 313

Discuss the ECM and cell adhesion in the context of disease processes.

Answer 313

to come