Essential Cell Bio Day 2

Question 1

General flow of an endocytic pathway

Answer 1

plasma membrane –> vesicles coated in clathrin –> early endosome –> golgi
early endosome –> late endosome –> lysosome

Question 2

How does pH change out of cell to the lysosome?

Answer 2

decreases to become more acidic
~7.4 –> 5.5

Question 3

What is clathrin?

Answer 3

protein coated, from transmembrane –> lumen of organelle

or from golgi–> seceretory vesicle

Question 4

Why are things protein coated ?

Answer 4

select things to be put in vesicles

Question 5

COP II coatomer

Answer 5

ER –> golgi

Question 6

COP I coatomer

Answer 6

cis golgi –> ER

Question 7

Constitutive Endocytosis

Answer 7

ALWAYS ON
receptor can be brought in without ligand
ie. LDL and transferrin

Question 8

Regulated Endocytosis

Answer 8

receptor HAS to be activated by ligand for it to be brought in

ie. EGF receptor

Question 9

Transferrin Receptor

Answer 9

brings in iron… iron needs pH 7.4 outside of cell to bind, then needs lower pH of 5 ish to be released

1) transferrin binds to iron outside of cell and brings it to membrane receptor
2) receptor + transferrin/ iron brought to early endosome –> iron released out of early endosome, and receptor + transferrin recycled to surface
3) nothing goes to late endosome / lysosome

Question 10

LDL receptor

Answer 10

1) LDL binds receptor at cell surface
2) LDL with receptor brought inside cell, LDL released INTO early endosome, receptor recycled to surface
3) LDL ligand goes into late endosome then lysosome –> in lysosome cholesterol is released out and proteins degraded

Question 11

EGF receptor

Answer 11

ligand (EGF) binds receptor–> receptor and ligand brought to early endosome –> BOTH borught to late endosome–> BOTH brought to lysosome, then both degraded there

Question 12

How does a vesicle know where to go / what to have???

Answer 12

1) protein coat (selects things to be put in vesicle)
2) v-snare and t-snare fusion (where to go)

Question 13

Steps of vesicle budding from donor membrane to acceptor membrane (include GTPases, snares)

Answer 13

1) Rab GTPase attaches to budding vesicle to perform work… v-snare present on budding vesicle off donor membrane with protein coat, dynamin can pinch off vesicle
2) protein coat sheds as vesicle moves to acceptor membrane
3) docking: v-snare on vesicle attaches with t-snare on acceptor membrane, GTPase on vesicle attaches with Rab effector (tethering protein– which has to be there first )
4) GTP is recycled, snares released and fusion to acceptor membrane

Question 14

What organelles have non-traditional vesicular mechanisms?

Answer 14

1) peroxisomes
2) chloroplasts
3) mitochondria

nuclear encoated proteins, DO NOT GO THROUGH ER ROUTE

Question 15

Why does the neuron have a special endocytic mechanism?

Answer 15

FAST

Question 16

what do lysosomes do and what are their features?

Answer 16

degrade: cell components, material internalized from extracellular environment
features: single membrane, pH of lumen around 5 (compartmentalization), acidic hydrolases carry out degradation reactions (HUGE diversity of enzymes)

Question 17

Autophagy and disease

Answer 17

when lysosome degrades internal structures

pieces of ER membrane engulf cytosolic proteins and organelles and fuse with lysosome

related to PD (removing protein aggregates by increasing autophagy)

Question 18

Peroxisomes and disease

Answer 18

are small, membrane-enclosed vesicles that provide a contained environment for reactions in which hydrogen peroxide, a dangerously reactive chemical, is generated and degraded

ie. Zellweger syndrome (can’t import proteins into peroxisomes)

Question 19

What is budding off the inner surface of the plasma membrane?

Answer 19

Electron micrograph showing numerous clathrin-coated pits and vesicles budding from the inner surface of the plasma membrane of cultured skin cells

Question 20

familal hypercholesterolemia

Answer 20

cell cannot recognize they already have cholesterol (LDL or diet) and continuously make endogenous cholesterol

leads to increased blood cholesterol levels and early life heart attacks

Question 21

autosomal dominant vs. autosomal recessive FH

Answer 21

dominant: 90%, LDL receptor mutation
recessive: mutation in adaptin protien, 2 alleles needed

Question 22

adaptin

Answer 22

protein between LDL receptor and clathrin coated pit

Question 23

How does circulating cholesterol modulate cholesterol synthesis and what happens in disease state?

Answer 23

NEGATIVE feedback

so typically, LDL receptors–> lysosome–> cholesterol is released, then it tells the cell that enough cholesterol is there and tells it NOT to produce new cholesterol

Question 24

HMG Coa Reductase

Answer 24

RLS in cholesterol synthesis

Question 25

How do statins work?

Answer 25

inhibit HMG CoA reductase to decrease new cholesterol synthesis and they increase LDL receptors to capture more LDL

Question 26

Discovery of statins

Answer 26

lovastatin + compactin= similar, lovastatin had some temporary stalling, but lovastatin was approved in 1987

cerivastatin= less favorable, more potent, more risks

Question 27

Treatment of statin examples

Answer 27

Heart protection study: simvastin good for women, decreased CHD risk, decreased myocardial infarction risk, decreased stroke risk

found decreased risk in vascular risk of patients with NO CHD, cerebrovascular peripheral vessel disease with NO CHD, pt > 70, lower LDL

Question 28

where can future statin treatments go?

Answer 28

combining with other agents because right now there is typically no reduction in LDL