Lecture 3

Question 1

what’s beta amyloid and what problems can arise from it?

Answer 1

it’s a transmembrane protein that helps with cell signaling, neuronal cell migration, synapse making, long term memory, and cell adhesion
-if there is abnormal cleavage of beta amyloid, we get an aggregation of A beta peptide in neuronal tissue that makes it resistant to proteolysis and causes ALZHEIMERS!

Question 2

What are normal prion proteins PrP?

Answer 2

cell surface proteins in alpha helix form that are neuroprotective against ischemia and control circadian rhythms
serve to organize the myelin sheath

Question 3

Creutzfeldt- jakob disease

Answer 3

normal prion protein gets converted to a variant that has the prion cross linked and resistant to proteolysis as a beta pleated sheet
the variation also INFECTS other PrP’s to convert to the variant
-ataxia, dementia, paralysis, death

Question 4

protein pumps definition plus example

Answer 4

transport proteins that require direct expenditure of energy to bring things into and out of the cell
EX) Na-K pump needs ATP to bring 3 molecules of Na out of the cell and allow 2 K into the cell to regulate intracellular volume

Question 5

Carriers

Answer 5

Carrier proteins transport things inside and out of the cell without the use of energy

Question 6

Digoxin

Answer 6

inhibits the NA/K pump and increases the amount of Na in the cell. Because there is a lot of Na in the cell, there is a decrease in activity of NA/Ca pump that allows Na into the cell. This increases intracell Ca.
- used in CHF because more Ca in sarcoplasm allows more Ca increases the chronotropic affect of the heart

Question 7

Example of secondary active transport

Answer 7

Na and glucose going down Na’s concentration gradient (no energy)
BUT: To maintain gradient, Na coming in with glucose is transported by Na/k pump out to the extracellular space with DOES require energy (secondary active tx)

Question 8

What’s MDR-1?

Answer 8

• multi-drug resistant transporter
• in kidney, intestine, liver. blood-brain barrier
• Transports drugs

Question 9

What happens when MDR-1 is over expressed?

How do you fix it?

Answer 9

cancer can cause increase in MDR1 receptors and cause the cytotoxic drug (chemo) therapy to be transported out of the cell quickly, rendering the cell resistant to chemo
-target the RNA that’s translated into MDR-1 and inhibit MDR1 translation or pharmacologic inhibitors

Question 10

What’s MDR-2 and what’s a disease that arises from a defective MDR-2?

Answer 10

• transports conjugated bilirubin from hepatocytes to bile canaliculus to be excreated
• genetic disorder called Dubin-Johnson Syndrome which is asyptomatic but causes an increase in conjugated bilirubin in the plasma because of a mutation in MDR2 that causes it to be mislocated and have impaired translation- benign

Question 11

MDR-3

Answer 11

• Expressed in the liver
• flippase (transfers phospholipids) of phosphatidylcholine where if flips it to outer canalicular membrane of hepatocytes so that they can be excreted in the bile

Question 12

Aquaporins

What’s aquaporin 2?

Answer 12

water protein channels

aquaporin-2: expressed in renal collecting tubule cells and used for water reabsorption

Question 13

Vasopressin

Answer 13

Antidiuretic hormone (ADH)
causes translocation of aquaporin receptors to the plasma membrane of the collecting tubule cell
-this causes an increase in reabsorption of water across the apical domain of the tubule cells (therefore, anti diuretic and pressor)

Question 14

Nephrogenic diabetes

Answer 14

results when both aquaforin 2 genes are inactivated by mutations; concentrated blood

Question 15

What’s the CFTR channel? what condition is associated with it?

Answer 15

CFTR is a Chloride channel and also regulates Na and biarb

Cystic fibrosis arises from CFTR probs- ductus deferens, lungs etc obstructed

Question 16

proteins on cell surface can help with digestion. Give an example and list it’s associated problem.

Answer 16

Lactase is a digestive enzyme that breaks down lactose so a decrease causes lactose intolerance with associated gas and bloating

Question 17

What are linker proteins?

Answer 17

Linker proteins are used to link plasma membrane to cytoskeleton to help with STRUCTURAL SUPPORT.

Question 18

Duchenne’s muscular distrophy

Answer 18

• xlinked recessive disorder that causes problems with distrophin gene
• problem with linker proteins not binding the plasma membrane to the cytoskeleton and maintaining structural support of the cell

Question 19

What are antigens exactly?

Answer 19

cellular identification tags, proteins

Question 20

glycolipids/ glycoproteins

Answer 20

carbohydrates (oligosaccharides) attached to lipids and proteins

Question 21

why do you feel dehydrated when you are drinking?

Answer 21

Because alcohol messes with your ability to use ADH and thus instead of retaining water, you pee it out and get dehydrated

Question 22

ganglioside gm1

Answer 22

a receptor for the cholera toxin
a glycoprotein
-allows cholera to enter the cell and increase cAMP
-increase in cAMP activates Cl- channel and gets Cl out of cell
-with Cl comes Na, Bicarb and water
= diarrhea

Question 23

what do proteins do with their charge?

Answer 23

they are negatively charged so they repel other negative charges
ex) keep rbc’s apart

Question 24

what are the four ways you can transport things across the plasmalemma?

Answer 24

1) endocytosis
2) exocytosis
3) porocytosis
4) exosomes

Question 25

what are the 5 distinct pathways of endocytosis?

Answer 25

``` macropinocytosis clathrin-mediated endocytosis non coated mediated endocytosis caveolae mediated endocytosis phagocytosis ```

Question 26

Macropinocytosis

Answer 26

- endocytosis - actin based - non specific ingesting of fluid and solutes (macro) - triggered by bacteria - occurs in thyroid cells (take up throglobulin) and dentritic cells (for immune surveillance)

Question 27

Clathrin-mediated endocytosis

Answer 27

- at clatherin coated pits often on lipid rafts - GTPase called dynamin required to pinch off vesicle with ligand-bound receptors in order to being it into the cell - MAY OR MAY NOT be mediated by receptors that increase specificity of what's endocytosed. - becomes uncoated once inside the cell so cell can use whatever was brought in

Question 28

what are 2 examples of a clatherin-mediated endocytosis?

Answer 28

1) cholesterol in the form of LDL enters the cell thru a clatherin coated pit 2) Protein Hormones

Question 29

What are located in coated pits?

Answer 29

cargo (ligand) receptors are bound to adaptin that is then bound to clathrin

Question 30

How does salmonella typhimurium enter the cell?

Answer 30

macropinocytosis (endocytosis)

Question 31

What are two examples of non-coated mediated endocytosis?

Answer 31

Cholera | shiga toxin

Question 32

what's an example of caveolae- mediated endocytosis?

Answer 32

Uses caveolin protein to bring things into the cell | simian virus 40 (was in polio vaccines) thought to cause tumor growth (no evidence)

Question 33

Phagocytosis

Answer 33

``` ingestion of large particles mediated by zipper mediated receptors Depends on actin no clathrin fuse with lysosomes ```

Question 34

What part of the plamalemma does cholera use to enter the cell?

Answer 34

glycolipid

Question 35

what happens in familial hypercholesterolemia?

Answer 35

There is a mutation in LDL receptor being able to bind adaptin and the clathrin coated sheath which leads to an poor uptake of LDL into the receptor, increase in LDL in plasma and ultimately hypercholesterolemia

Question 36

what kinds of cells use macropinocytosis?

Answer 36

thyroid cells | dentritic cells