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

Lecture 17: Cholesterol Homeostasis Flashcards

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
Q

drugs that control cholesterol levels target _____

A

-elimination of bile salts
-level of LDL receptor
-de novo synthesis

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26
Q

statins are drugs that ____

A

inhibit HMG-CoA reductase (enzyme that produces cholesterol)

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27
Q

statins reduces ____

A

level of cholesterol

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28
Q

PCSK9 is _____ that activates ____

A

a trafficking mediator for the LDLR (LDL receptor)
itself by cleavage

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29
Q

dominant-negative mutant of PCSK9 doesn’t act as _____

A

a trafficking mediator

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30
Q

gain-of-function mutant of PCSK9 increases ______ (2)

A

action of trafficking mediator
degradation of LDLR in the lysosome

31
Q

PCSK9 is a protein in the ___ that interacts with ____ and then targets it for ______

A

ER
LDL receptor
lysosomal degradation

32
Q

hypercholesterolemia (def.)

A

high levels of LDL

33
Q

PCSK9 inhibitors prevent ____

A

degradation of LDLR, reducing [cholesterol] in serum

34
Q

genes regulated by sterols contains ____

A

unique sequence (SRE - sterol regulatory element)

35
Q

nucleotide important in SRE for interaction with transcription factor

A

cytosine

36
Q

transcription factors (proteins) that recognize SRE

A

nSREBP

37
Q

SREBP is localized where when inactive?

A

ER

38
Q

SREBP (descr.)

A

transmembrane protein
large protein with two hydrophobic membrane spanning domains

39
Q

SREBP activity when cholesterol is present?

A

SREBP interacts with SCAP protein (transmembrane) which interacts with INSIG in ER

40
Q

SREBP activity when cholesterol is absent?

A

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
Q

SCAP-SREBP complex trapped in ER by ___

A

INSIG

42
Q

SCAP binds to cholesterol and prevents ____

A

entry into COPII vesicle to golgi

43
Q

nSREBP is in ____

A

nucleus

44
Q

SREBPs promote synthesis of ____

A

1) enzymes responsible for cholesterol synthesis
2)production NADPH - needed for lipid synthesis
3) LDL receptors

45
Q

↑ nSREBP in nucleus = ↑ ___

A

transcription of genes for HMG-CoA reductase and LDL receptor

46
Q

SREBP vs nSREBP

A

inactive vs active

47
Q

nSREBP is located where on inactive SREBP?

A

globular domain at N-terminus (n=nuclear or N-term) -cytoplasmic

48
Q

release of nSREBP involves _____

A

two specific proteases

49
Q

proteolysis of SREBP happens in ___

A

golgi

50
Q

Site 1 protease (S1P) cleaves ___

A

lumenal loop (in golgi lumen)

51
Q

Site 2 protease (S2P) cleaves ____

A

within the first transmembrane anchor

52
Q

nSREBP acts as ____

A

transcriptional facot

53
Q

nSREBP rapidly degraded by ____

A

proteasome in Ub-dependent manner

54
Q

SREBP processing by S1P requires presence of _____

A

SCAP

55
Q

mutations in SCAP that prevent binding to SREBP also prevent ___

A

processing

56
Q

formation of complex with SCAP stabilizes ___

A

SREBP

57
Q

____ domain of SREBP on _____ interacts with ___ domain of SCAP on ____

A

Regulatory
C-terminus
WD
C-terminus

58
Q

SCAP (descr..)

A

polytopic membrane protein (8 transmembrane domains) with two important domains

59
Q

Two domains of SCAP

A

-c-terminal WD domain
-n-terminal domain

60
Q

c-terminal WD domain of SCAP located in _____

A

cytoplasm

61
Q

c-terminal WD domain of SCAP contains multiple ____

A

W,D residues,

62
Q

n-terminal domain of SCAP contains ____

A

8 trans-membrane segments

63
Q

n-terminal domain of SCAP: helices 2-6 form ___

A

sterol sensing domain (SSD)

64
Q

SSD of SCAP binds to binding partner in ER which ___

A

anchor complex

65
Q

overexpression of SCAP with SSD causes ___

A

formation of golgi complex

66
Q

TM1-6 (transmembrane) of SCAP binds to ___

A

INSIGs (1 &2)

67
Q

INSIG (def.)

A

Insulin Induced Gene

68
Q

INSIG is localized to ___

A

ER

69
Q

INSIG binds SSD of SCAP in ____

A

the presence of cholesterol

70
Q

SCAP dissociates from INSIG and is exported to golgi in ____

A

absence of cholesterol

71
Q

High cholesterol: SREBP-SCAP complex

A

-cholesterol-binding alters SCAP structure
-SREBP-SCAP complex binds INSIG
-complex trapped in ER

72
Q

Low cholesterol: SREBP-SCAP complex

A

-SREBP-SCAP complex released from INSIG
-become free to interact with COPII (Sec24)
-transported to golgi

73
Q

SCAP is ___ (slang) while INSIG is ____ (slang)

A

-sensor
-anchor

z:Cell 300 (17 decks)

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