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z:Cell 300 > Lecture 17: Cholesterol Homeostasis > Flashcards

Lecture 17: Cholesterol Homeostasis Flashcards

(73 cards)

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1
Q

cholesterol (descr.)

A

relatively flat molecule

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2
Q

cholesterol play an important role in ____

A

determining membrane integrity and fluidity (biological properties of PM)

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3
Q

cholesterol vs. phospholipid amount at PM

A

equimolar (equal amount of cholesterol and phospholipid)

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4
Q

cholesterol location in PM/ER

A

restricted to subdomains

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5
Q

cholesterol synthesized where?

A

ER

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6
Q

cholesterol in membrane forms _____ which creates ______

A

lipid rafts
microdomain for signaling

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7
Q

role of cholesterol for membranes

A

-with sphingomyelin, it forms rafts and caveolae
-serves as precursor for sex hormones, bile acids

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8
Q

lipid rafts and caveolae is important for ____

A

cell signaling and endocytosis

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9
Q

lipid rafts and caveolae = cholesterol + _____

A

sphingomyelin

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10
Q

dysregulation of cholesterol leads to ____

A

important pathologies

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11
Q

cholesterol comes from ____ or _____

A

diet or produced by cell (de novo synthesis)

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12
Q

↓ cholesterol = ↑ ______

A

enzymes that make cholesterol

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13
Q

removing cholesterol induces _____

A

transcription of many enzymes involved in cholesterol synthesis

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14
Q

presence of cholesterol blocks ____

A

transcription of genes implicated in cholesterol synthesis and endocytosis of LDL

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15
Q

presence of cholesterol promotes degradation of ___

A

enzyme involved in cholesterol synthesis

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16
Q

enzyme involved in cholesterol synthesis: ___

A

HMG-CoA reductase

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17
Q

esterified cholesterol (CE) traffics between ___

A

organs in specialized particles

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18
Q

dietary cholesterol is trafficked in __

A

Chylomicrons

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19
Q

bad cholesterol is trafficked in ___

A

VLDL, LDL

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20
Q

good cholesterol is trafficked in ___

A

HDL

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21
Q

CE is highly ____

A

hydrophobic

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22
Q

organ important for cholesterol metabolism

A

liver

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23
Q

VLDL, LDL transports excess fat from ___

A

liver to artery

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24
Q

HDL transports excess fat from ___

A

artery to liver

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25
drugs that control cholesterol levels target _____
-elimination of bile salts -level of LDL receptor -de novo synthesis
26
statins are drugs that ____
inhibit HMG-CoA reductase (enzyme that produces cholesterol)
27
statins reduces ____
level of cholesterol
28
PCSK9 is _____ that activates ____
a trafficking mediator for the LDLR (LDL receptor) itself by cleavage
29
dominant-negative mutant of PCSK9 doesn't act as _____
a trafficking mediator
30
gain-of-function mutant of PCSK9 increases ______ (2)
action of trafficking mediator degradation of LDLR in the lysosome
31
PCSK9 is a protein in the ___ that interacts with ____ and then targets it for ______
ER LDL receptor lysosomal degradation
32
hypercholesterolemia (def.)
high levels of LDL
33
PCSK9 inhibitors prevent ____
degradation of LDLR, reducing [cholesterol] in serum
34
genes regulated by sterols contains ____
unique sequence (SRE - sterol regulatory element)
35
nucleotide important in SRE for interaction with transcription factor
cytosine
36
transcription factors (proteins) that recognize SRE
nSREBP
37
SREBP is localized where when inactive?
ER
38
SREBP (descr.)
transmembrane protein large protein with two hydrophobic membrane spanning domains
39
SREBP activity when cholesterol is present?
SREBP interacts with SCAP protein (transmembrane) which interacts with INSIG in ER
40
SREBP activity when cholesterol is absent?
SREBP interacts with SCAP protein (transmembrane) in ER SCAP-SREBP complex moves to Golgi proteolysis of SCAP-SREBP produces transcription factor which moves to nucleus -> affects gene expression
41
SCAP-SREBP complex trapped in ER by ___
INSIG
42
SCAP binds to cholesterol and prevents ____
entry into COPII vesicle to golgi
43
nSREBP is in ____
nucleus
44
SREBPs promote synthesis of ____
1) enzymes responsible for cholesterol synthesis 2)production NADPH - needed for lipid synthesis 3) LDL receptors
45
↑ nSREBP in nucleus = ↑ ___
transcription of genes for HMG-CoA reductase and LDL receptor
46
SREBP vs nSREBP
inactive vs active
47
nSREBP is located where on inactive SREBP?
globular domain at N-terminus (n=nuclear or N-term) -cytoplasmic
48
release of nSREBP involves _____
two specific proteases
49
proteolysis of SREBP happens in ___
golgi
50
Site 1 protease (S1P) cleaves ___
lumenal loop (in golgi lumen)
51
Site 2 protease (S2P) cleaves ____
within the first transmembrane anchor
52
nSREBP acts as ____
transcriptional facot
53
nSREBP rapidly degraded by ____
proteasome in Ub-dependent manner
54
SREBP processing by S1P requires presence of _____
SCAP
55
mutations in SCAP that prevent binding to SREBP also prevent ___
processing
56
formation of complex with SCAP stabilizes ___
SREBP
57
____ domain of SREBP on _____ interacts with ___ domain of SCAP on ____
Regulatory C-terminus WD C-terminus
58
SCAP (descr..)
polytopic membrane protein (8 transmembrane domains) with two important domains
59
Two domains of SCAP
-c-terminal WD domain -n-terminal domain
60
c-terminal WD domain of SCAP located in _____
cytoplasm
61
c-terminal WD domain of SCAP contains multiple ____
W,D residues,
62
n-terminal domain of SCAP contains ____
8 trans-membrane segments
63
n-terminal domain of SCAP: helices 2-6 form ___
sterol sensing domain (SSD)
64
SSD of SCAP binds to binding partner in ER which ___
anchor complex
65
overexpression of SCAP with SSD causes ___
formation of golgi complex
66
TM1-6 (transmembrane) of SCAP binds to ___
INSIGs (1 &2)
67
INSIG (def.)
Insulin Induced Gene
68
INSIG is localized to ___
ER
69
INSIG binds SSD of SCAP in ____
the presence of cholesterol
70
SCAP dissociates from INSIG and is exported to golgi in ____
absence of cholesterol
71
High cholesterol: SREBP-SCAP complex
-cholesterol-binding alters SCAP structure -SREBP-SCAP complex binds INSIG -complex trapped in ER
72
Low cholesterol: SREBP-SCAP complex
-SREBP-SCAP complex released from INSIG -become free to interact with COPII (Sec24) -transported to golgi
73
SCAP is ___ (slang) while INSIG is ____ (slang)
-sensor -anchor

z:Cell 300 (17 decks)

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