exam 4 Flashcards
1
Q
Major component of plasma membranes
A
glycerophospholipids
2
Q
parts of lipids
A
space filling hydrocarbon tail kinks glycerol phosphate coline
3
Q
Sphingolipids
A
no kink, bent over head
sphingomyelin
cerebrosides and gangliosides
4
Q
two cerebrosides
A
galactocerebrosides
glucocerebrosides
5
Q
gangliosides
A
most complex sphingolipid
can act ac receptors
lots in brain
6
Q
cholesterol
A
slips between lipids
amphiphilic
more cholesterol more rigidity
7
Q
fluidity and melting point
A
above Tm is more fluid than below
8
Q
transverse vs lateral
A
transverse is flipping and flopping inner to outter and is slower than lateral
9
Q
saturation and fluidity
A
more double bonds means more unsaturation means more fluid because less tighlty packed
10
Q
lenght and fluidity
A
longer tails less fluid
11
Q
cholesterol and fluidity
A
more means less fluid
12
Q
integral membrane proteins
A
detergent to separate
13
Q
peripheral membrane proteins
A
loosely associated so removed via pH or salt change
14
Q
3 typs of lipid anchors
A
prenylation
fatty acytalated
GPI
15
Q
prenylation
A
iso-prenoid attatched to Rab proteins to be activated at membrane
16
Q
rab proteins
A
just taxi proteins that mediate attachment to motor proteins
17
Q
myristolation
A
type of fatty acid lipid anchor prevalent in HIV protein
18
Q
Palmatic acid
A
lipid acnchor attached to cystein with thioseter linkage
19
Q
GPI
A
largest most complexe lipid anchor
can act as a receptor for signalling
20
Q
Fluid mosaic model
A
membrane proteins as icebergs floating in sea of lipids
21
Q
lipid asymmetry
A
inner vs outter leaflet differences maintained by flippases
PS is example
22
Q
lipid rafts
A
membrane microdomains with lots of cholesterol and bound proteins important for signalling
23
Q
molecules that can cross unaided
A
gases
small polar
super small non polar
24
Q
molecule that need help
A
charged
large uncharged
most biologicaliy important things
25
connexin
factilitates gap junctions
| for communication more than transport
26
simple diffusion
just concentration gradient
27
Ficks law trends
bigger gradient faster move
| shorter distance faster move
28
partition coefficient
compares solubility in oil/water to see how well get through
hydrophobic K>1 gets through better because not blocked by membrane
29
overtons law
higher lipid solubility = higher permeabiltiy
30
simple diffuision
slide through on own
| ion channels count
31
facilitated diffusion
no energy still, needs protein channels for big stuff
32
primary active transport
needs energy to go against gradient
| like Na pumping out
33
secondary active transport
indirect energy usage like Na is primary out but as it comes in it brings something else back in with it against the passengers gradient
34
uniports
facilitated
rocking banana or alternating access
changes affinity to catch one side and release other
logarithmic rate toward Vmax with RMS
35
symports
usually secondary active transport
like for sodium and glucose
SAME DIRECTION
36
vSGLT
symport for prok
| same structure just varying specificity
37
antiports
active again
move in OPPOSITE DIRECTIONS
use alternating access
38
Na Ca exchanger
Na going in helps get Ca out
39
blocking Na/K pump's effect on NA/CA exchanger
Na doesnt go out so it cant come back in so it cant help Ca get out so increased contractivity of heart (cant relax)
40
Na/H pump
pH changes
41
CI/HCO3
for CO2 exchange
42
channels for simple diffusion
just a hole so fast
| can be gated
43
p type pumps
ATP -> ADP and P changes pump convermation
44
NA/K pump
3 Na out, 2 K in
45
SERCA
Ca pump to get Ca bac into SR of ER
46
F type
movement of H makes ATP based on gradient
found in mitochondria
still counts as active?
47
V class
acidyfies lysosomes
| brings H in using energy
48
ABC transporter
highly specific waste disposal
uses 2 ATP
can improve -- get too good at removing drug so it creates resistence
49
CFTR
cystic fibrosis when reduced water movement
50
simple vs facilitated kinetics
linear vs log
51
characeteristic of secondary active transport
movement of one ion down its concentration gadient drives uphill movement of another
52
H/K pump
puts H in stomach to acidify
| block it and increase pH
53
carriers vs channels
bind and change vs open and flow
54
Nernst potential
depends on ionic charge
K and Cl are close to resting potential
Na and Ca are not
55
driving force
combination of concentration gradient and electrochemical gradient
56
membrane potential
Vm is the charge difference based on ion imbalance
57
Vm changes
depends on what has the greatest permeablity so like at rest its closer to the Ex of K beacause of leak channels but when Na channels get ungated and Ena >>>Ek then Vm goes toward Ena
58
Vm
move in
59
Vm>Ex for cations
move out
60
Vm trends for anions
opposite of cations
61
refractory period
Na inactivation
absolute during repolarization and cant open
relative during hyperpolarization and needs extra stim
makes one directional
62
stimulating electrodes
add current, see what happens
63
TTX
pufferfish example fo closing Na channels
64
ionic conductances
Na is voltage dependent, two gates one to be activated and one to inactivate
K is slower, can open but never inactivates
65
voltage gated channels
4 subunits with a hole in the middle
66
Synaptic transmission
pre side has lots of vessicels for NTs
| Ca goes in at pre to release vessicles
67
EPSP
increase in cation permeablity
ACh
serotonin
glutamate
68
NMJ
ACHr reacts to ACh to open
69
IPSP
increased nion permeability
GABA
glycine
70
what is responsible for RF
Na inactivation
71
reduce K leak channels
Vm moves towards Ena because Pna>>Pk
72
increase K extracellular
depolarization because loss of concentration gradient is basically the same as stopping leak channels because stops leaking
73
block ACh into vessicles
less ACh released so less AChR activation so lower amplitude
74
protein targeting
processs of proteins getting to their functional site
75
general mechanism of pt 3 steps
recognize signal
interact with receptor
NTP- dependent translocation across target membrane
76
co targeting
destined for secretion, PM, ER, golgi and lysosomes
77
post tagetign
nucleus, mitochondrion, peroxisome
78
secreted co targeting
ribosomes are translating
signal sequence on N terminal recognized by SRP and stops elongation
everything goes to SRP receptor on RER
hydrolysis of GTP on SRP and receptor puts polypeptide on Translocon sec 61 releacing SRP and translation resumes
signal peptidase removes signal sequence
translation ends and ribosome leaves and translocon closes
goes to golgi and then out if no other signals
79
ER co targeting
gets into ER and then to golgi in same way as secreted
| but KDEL is retrieval sequence that says come back to ER rather than secreted
80
lysosomes co targeting
get into ER normally
then glycosylated in lumen
Mannose residue is phosphorylated
M6P gets recognixed and goes in clathrin coated vessicles to sorting vessicles
low pH there removes GP and P is removed then go fuse with lysosome
81
post targeting to nucleus
after translation in cytosol NLS is recognized on proteins too big to go through pores
binds to importin and translocated through nuclear pore complex
Ran GTP binds to and removes importin from cargo, taking importin back out
hydrolysis of rand GTP releases importin in cytosol
NLS not cleaved
82
post targeting to peroxisomes
basically same as nucleus
PTS1 on C terminal tripeptide or PTS2 on N terminal
importins called peroxins
83
Signal sequence
10-40 aa with postive charge next to 6-12 hydrophobic aa
84
SRP
signal recognition particle with &S scRNA and 6 proteins
85
Sec61
translocon on RER
3 subunits
alpha helices arounda beta pore
86
integral membrane proteins
while moving through ER translocon have 22 aa stop transfer makes it open sideways can stay in ER but default is PM
87
NES
nuclear export signals
| protein with NES binds exportin and Ran GTP Hydrolyssi in cytosol releases all
88
NLS
nuclear localization sequence
| 4-8 aas anywhere in sequence, often internal not terminal
89
PTS1
SKL sequence on C terminal tripeptide for peroxisome post translational targetting
90
covalent modification
adding tuff to N or C terminus or R groups with covalent bonds
91
ADP- ribosylation
covalent examples
his residues
EF2 by diphtheria toxin
92
Phosphoylation
covalent examples
| of OH groups on Ser/thr/tyr residues on eIF2
93
Hydroxylation
covalent examples
| pro and lys residues on collagen
94
Ubiquitinatino
covalent examples
ubiquitin aded to lys
marks for degredation
95
Glycosylation
```
covalent examples
most common
addition of sugar to protein
N vs O
increases solubility
protects against proteolysis
spatial organization
recognition and antiginicity
```
96
Protein Lipidation
covalent examples
GPI to c terminus via amide bond
myrsitolation, palmitolation, prenylation
97
N linked glycosylation
to amide on asn of asn-x-thr/ser
14 branched sugars linked to dolichol phosphate
en bloc in ER
trimming in ER and some edits in golgi
98
O linked glycosylation
to OH gorups on ser or thr
in gOlgi stepwise starting with GalNAc
can happen in cytosol
99
colagen glycosylation
mostly O linked but N linked can be a part
100
myristoylation
on C terminun co trans and in non reversible
101
palmityolation and prenylation
on cystine
post trans
reversible
102
chaperones
protect against misfolding and aggregation
hsp70 bind to sections and are mitochondrial or cytosolic
hsp60 is the barrel for folding in mitochondria
Bip in in ER or UPR
103
disulfide bonds
spontaneius or because of PDI enzyme in ER
104
UPR
unfolded protein response
Ire1 or ATF integral of ERg have BiP in lumen which goes to unfolded so these can dimerize and splice mRNA to make more chaperones
or PERK can inhibit or selectively translate proteints by phosphorylating eiF2
or just let them degrade
105
peptide cleavage
remove initiating methionine
remove signal sequience making preproportein a proportein
proprotein to protein example is insulin
106
protein subunit association
just know that multimeric proteins form
107
insulin
mature is a dimer with two interchain disulfide bonds
preproinsulin in made in RER
met and signal sequinc removed in ER making proinsulin
proinsulin is packed into vesicale in golgi where an internal sequenc is removed making insulin
108
collagen
```
most abundent structural protein especially extracellular and bone/cartilage
fibrous, secreted glycoproteins
mostly trimers of alpha chains
Type I is main one
repeats of gly-x-y
```
109
collagen alpha cain
left handed helix of three aa per turn
three of these become triple helix of interchain H bonds
then covalent crosslinks make triple helices in to fibrils which associate into fibers
110
collagen synthesis
prepropeptide chains made in RER with three domains
hydroxylation of pro and lys
triple helix forms with disulfide bonds called procollagen
triple helix only happens if proline is hydroxylated then leaves ER
stuff happens in golgi and proprotein goes extracellular
globular C and N terminal cleavage making tropofollagen reducing solubility
corss links by lysyl oxidase make strong collagin fibrils
111
collagen defects and mutations
osteogenesis imperfecta
scurvy
ehlers danlos stretchy skin
112
TOM complex
translocater of the Outer Mithochondiral membrane
recognized signal sequence
takes to intermembrane space
ATP to remove cytosolic hsp 70
113
TIM23complex
either moves to matirx or inserts inner membrane
signal sequence comes off and folds in matrix
ATP to help mitochondiral hsp70 pull it in
if inserting then a stop is revealed after cleavage
114
TIM22 complex
inserts into inner membrane
| theres and internal signal sequence causignt this
115
SAM
folding within outer membrane for multipass stuff
| there are chaperones for intermembrane space
116
OXA
puts proteins made in matirx into the inner membrane
117
smooth vs rough ER
rough is where peptides get in either co or post
| smooth is where vessicles bud off and where sarcoplasmic reticulum is for Ca storage, also lipid met,and detox
118
microsomes
fragmented ER that can be rough or smooth from which part they came from but smooth harder to identify
119
separation of microsomes
homoginization to fragemnet
| ribosomes on rough ones are denser so they sink in equilibrium centrifugation
120
importance of microsomes in research
easier to separate and study different parts of ER
121
translation to ER
signal sequence to SRP to SRP-r to sec61 to inside and signal peptidase
122
single pass at ER
N terminal start
internal hydrophobic stop-transfer sequence
side with positive charge ends up in cytosol
123
Double pass at ER
internal signal sequence starts it
reaches stop toward C terminus
both ends in cytosol
124
multipass at ER
nearest hydrophobic to N is start transfer
then alternating start stop transfer untill all hydrophobic are in membrane
identical protein chains always have same orientation
125
ER resident protein retention
have ER retention signal KDEL at C terminus
| PDI and BiP are resident
126
post trans to ER
translocator needs accessory proteins like BiP to use ATP for pulling protein in
127
endocytosis
from outide to inside
| sorting signals and receptors on vesicle to know where
128
exocytosis
ER to golgi and out
129
anterograde transport
towards plasma membrane
| COPII ER to golgi
130
retrograde transport
toward ER
COPI ER to golgi
clathrin PM to endosome and golgi
131
proteins for intracellular vesicle movement
```
Coats: COPII ER to Golgi
COPI goligi to ER
Caltherin evertything else
adapter proteins for budding
also Dynamin
```
132
adapter molecules for vessicle movment
adaptoer proteins help clatherin select cargo and form vesicle
it goes clatherin binds adapotor binds protein/cargo receptor can be phospholipids
133
phosphatidylinostol PI and its role in forming vessicles
when phosphorylated it can bind to receptors and add specificity to vesicle formation
134
dynamin and vesicle formation
is a GTPase for pinching off vesicle
135
coat-recruitment GTPases vesicle formation
Arf and Sar1
when turned on a hydrophobic region is exposed which inserts into the membrane binds to sex23 then sec24 then cargo then sec13/14 then hydrolysis turns em off and release uncoated vessicel
136
G-binding proteins can be switched on an off
```
off with GDP
on with GTP
on is when inserts into membrane
GEF is in membrane (sec12 for sar1)
bunch turn on to recruit coat complex then hydrolyzed and turned off to remove coat after vesicle is formed
```
137
RAB proteins and vesicle movement
cycle between membrane and cytosol
GDP inactive
GTP active and associated with vesicle's RAB effector
vesicle tethered to target membrane with SNAREs
138
leaving ER
Use COPII
bind to cargo
coat forms
leave at exit sites which are ribosome free
need export signal
must be properly folded
vesicles fuse into vesicular tubular clusters and move to Golgi
139
returning to ER
bud off of golgi or vesicular tubular clusters with COPI coat
have KKXX for membrane and KDEL for ER soluble proteins like BiP
140
consitituitve vs regulated secretion
constitutive is when they just constantly go out
| regulated is when they form secretory granules and wait for signal to dump
141
two theories of Golgi organization
vesicular transport model - cisternae are static with vesicle in between
cisternal maturation model - whole cisternae moves forward sending its enzymes back and recieving new ones via vesicles
142
COPII
ER to golgi
sec23/24 outside
sec 13/31 inside
143
SNAREs
mediate fusion of vesicle with membranes
v-snare on vesicle
t-snare on target
helical domains wrap around each other making trans-SNARE complexes
144
Clatherin
PM to endosomes and golgi
| triskillion
145
COP II
ER to Golgi
anterograde
sar1
146
COPI
Golgi to ER
retrograde transport
Arf
147
KDEL pH
in low pH golgi they bind to receptors and get grouped for return vessicles, in neutral pH ER they are released back into lumen
148
T/F all proteins begin translation with ribosomes in cytosol
true
149
phagocytosis
uptake of large vessicles
prof and non prof
actin polymerization required
150
autophagy
enfulf cellular structures and digest
| can be good or bad
151
endocytosis
vesicular uptake
pinocytosis
clatherin dependent and independent
down regulates recepetors
152
professional phaocytes
neutrophils
macrophages
dendritic cells
153
non professional B lymphocytes
sometimes release antibodies instead
154
phagocyotissis steps
```
attraction (chemotaxis)
adherence
ingestion into phagosome
digestion/killing by linking with lysosomes
Elimination - discharge remains
```
155
eat me signal
CRT and TSP1 bind to LRP on phagocyte
C3b and C1q activate CRs
PS bind to stablin Tim or BAI actiating MerTK
inflamation cause more receptors on phagocytes and reactive oxygen species make eat me signals come out
156
dont eat me
CD47 binds SIRPalpha
| sialic acid residues bind receptors and block eat me
157
Oxygen dependent destruction of microbes
engulf then respiratory burst from ROS release via enzymes which can damage macromolecules
158
oxygen independent destrcution of microbes
anti microbial proteins and peptides
binding proteins
hydrogen ion transport
159
2 mech induce phago
zipper- things bind exterior
| trigger - things get injected and bind interior
160
role of macroautophagy
housekeeping
host defense
development
stress response
161
main steps of macroautophagy
```
isolation membrane forms
expands
completes (fullly formed autophagosome)
fuses with lysosome
degrade
efflux
```
162
Atg8 or LC3
covalenty links to PE in autophasomal membraen
163
pre autophagosomal sturcture tragteting complex order
```
atg1
atg9
PI3K
Atg2-18
Atg12
atg8
```
164
autophagy complex signalling
ULK1 - induciton
PI3k forms phagosphere
elongation by LC3II
fusion with lysosome for enzymes
165
selective autophagy
p62 for binding LC3 on phagosoome lots of p62 when defects
| parkin ubiquitinates
166
5 steps of endocytosis
nucleation - inductiong curvature
cargo selection by AP2
clathrin coat assembly -polymerization of clatherin triskelia via AP2
vesicle scission - BAR recruits dynamin, GTP hydrolysis
uncoating and clatherin recycling - HSC70 and cofacter dissasembrl
167
purposes of endocytosis
internalize receptors
regulate signals
synaptic vesicle recyclying
168
what is the purpose of protein degredation
quality control and aggregation prevention
| also regulation of cell processes
169
differences between lysosomal protein degredation and proteasomal protein degredation
lysosome - extracellular and non selective
| proteasome - intracellular and selctive (only ubiquitinated)
170
what does a proteasome do
degrades proteins that hae a ubiquitin tag
| all three parts known as 26s preteosome cuz biology dont care
171
what is the role of 19S cap
its on either side of 20s and it has ATPases for pushing and unfolding proteins into the 20s
172
role of 20s cylinder
this is where the protealytic activity occurs
173
proteasome target recognition
occurs in 19s Cap
174
proteasome target degredation
d
175
target protein ubiquitination
ubiquitin activating enzymes E1 gets turned on by covalent glycine linkage to ubiquitin
ubiquitin conjugating enzymes E2 and E3 bind to E1 and replace it and keep ubiquitin
ubiquitin ligase E3 has high specificity and binds degredation signal on target protein and give it ubiquitin
cycle repeats for polyubiquitination
E4 can escort and/or proofread on way to proteosome
176
purpose of ubiquitinatino
a tage for getting to protesome for degredation and process ocntrol
also modifies biochemical properties
177
misfolded protein recognitino by E3
500 E3s so highly specific
| ligase can be activated several ways
178
normal protein recognition by E3s
degredation signal has to be activated first
179
selective ubiquitination for specific and selective proteolysis
same thing with a lot of specific E3s
180
mechanisme and consequences of protein aggregations
forming cross beta filament in prions disease as normally hidden regions interact
181
role of ubiquitin like modifiers
get added in similar ways but are for modifications not for degredation signals
