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cholesterol Flashcards

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1
Q

what are the four major classes of lipoprotein particles?

A

chylomicrons -
VLDL
LDL
HDL

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2
Q

What are the lipid components of lipoproteins?

A

triglycerols
cholesterol esters
phospholipids

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3
Q

what are the protein components of lipoproteins?

A

apolipoproteins A-E

activates lipid processing enzymes in blood.

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4
Q

what are the “bad” lipoprotein particles?

A

chylomicrons
VLDL
IDL
LDL

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5
Q

what are the “good” lipoprotein particles?

A

HDL
HDL in high levels reduce cardiovascular disease because it extracts cholesterol and cholesterol esthers from cell membranes, vasculature, and atherosclerotic plaques and return them to the liver

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6
Q

why are LDL bad?

A

increasese cardiovascular disease and stroke

promotes fatty deposits in arteries which reduces or blocks blood flow and oxygen delivery

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7
Q

what is hyperlipidemia?

A

elevated plasma cholesterol/triglycerides

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8
Q

Describe chylomicrons metabolism

A
  1. Made in the intestine and contain apo B48
  2. chylomicrons are released into lymph
  3. Chylomicrons acquire apo-CII and apo-E from HDL in plasma
  4. lipoprotein lipase on surface on non hepatic tissues hydrolize triglycerides
  5. chylomicron remnants of depleted of glycerol and FFA transfer apo C-II back to HDL
  6. Remnants w/apoEand apoB48, bind to the apo E receptor on liver cells, resulting in the uptake of remnants
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9
Q

what binds lipoprotein particles?

A

cell surface receptors

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10
Q

what happens when intracellular cholesterol increases?

A

expression of cholesterol synthesis gene is blocked

HMG CoA reductase is down regulated

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11
Q

what are the LDL receptor mutations and what do they all lead to?

A

Class 1 - no receptor synthesized
Class 2 - receptors synthesized but remains in ER or Golgi
Class 3 - receptors lack normal LDL binding
Class 4 - receptors are not clustered in coated pits and endocytosed
They all lead to high blood cholesterol levels

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12
Q

how is extra cholesterol stored ?

A

stored as cholesterol esters in lipid droplets in the cytosol

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13
Q

what is pcsk9?

A

a new drug target for ldl cholesterol reduction that binds the ldl receptor and stimulates ldl receptor endocytosis

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14
Q

non functional ldl receptors

A

makes ldl stay longer in blood stream which increases blockage in the arteries as the plaque hardens and narrows the arteries

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15
Q

Does PCSK9 increase or decrease the levels of LDL receptor at the plasma membrane?

A

PCSK9 reduces the level of cell surface LDL receptors, thus decreasing the rate of LDL removal and elevating plasma LDL.

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16
Q

Do anti-PCSK9 antibodies increase or decrease the levels of LDL receptor at the plasma membrane? Why?

A

increases levels of ldl receptors because it allows the ldl receptors to remain and bind to ldl for degradation

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17
Q

Does PCSK9 block the binding of LDL to the LDL receptor?

A

? idk becaus does not bind where the ldl binds but it makes it get endocytosed so technically the receptor is still open to bind to the ldl

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18
Q

When cholesterol levels are low, where is SCAP-SREBP?

A

SCAP AND SCREBP move to th golgi and then SREBP is cleaved. cleaved SREBP moves to nucleus to activate genes for cholesterol synthesis.

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19
Q

When intracellular cholesterol levels are low, is HMG CoA reductase phosphorylated or unphosphorylated?

A

unphosphorlyated because it activates HMGR (HMGR CoA reductase) which increases formation of cholesterol needed in a low level environment

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20
Q

When is HMG CoA reductase likely to be degraded?

A

when cholesterol is high. HMGR gets misfolded and degraded by 26S proteasome

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21
Q

What organ STORES bile acids and bile salts?

A

gallbladder

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22
Q

What is the rate limiting step in bile acid synthesis?

A

cholesterol) 7-a-hydroxylase

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23
Q

what does Apo B100 do?

A

helps bind lipoprotiens to LDL receptor

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24
Q

what does Apo CII do ?

A

works on lipoprotein lipase to cut fats

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25
Q

define phoshatidic acid

A

the simplest phospholipid, a precursor of other phosholipids

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26
Q

where are phospholipids synthesized?

A

in the ER

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27
Q

what is phospholipid cardiolipin?

A

2 phosphatidic acid esterified at ther phosphate groups to glycerol
made in mitochondria
antigenic (immunogenic -solicits immune response)

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28
Q

what is sphingolipids?

A

it is an amino alcohol with long hydrocarbon tail
has sphingosine backbone
made of ceramide
made in Golgi

29
Q

membrane bilayers are not…?

A

symmetric and homogenous

30
Q

phosphatidylserine has more of ?

A

more inner monolayer than outer monolayer

31
Q

define P-type ATPases

A

move lipids to inner leaflet

32
Q

define ABC transporters

A

move lipids to outer leaflet

33
Q

define scramblase

A

moves lipids bi-directionally

34
Q

define Bi-directial flippase

A

ATP independent (doesnt need ATP)

35
Q

hallmarks of apoptosis?

A

exposes phosphatidylserine (PS) on outer face of plasma membrane (this helps apoptotic cells be recognized by phagocytes)
atp - dependent
fragment nucleus and dna

36
Q

what is Mitoycin C?

A

an anti cancer agent because it fragments nucleus

37
Q

what causes dna laddering by mitomycin c?

A

cleavage occurs between nucleosomes cause laddering effect

38
Q

why does asymmetry of phosphatidylerine (PS) matter?

A

cell surface expression of PS during apoptosis

39
Q

define lipid rafts

A

microdomains in membrane bilayers

40
Q

what is the structure of phospholipids?

A

hydrophobic tail made of 2 fatty acylchains
3 carbon backbone made by glycerol
polar head group made by an alcohol

41
Q

what is lamin A?

A

nuclear protein

42
Q

what is progerin?

A

abnormal nucleus

43
Q

what is the importance of FRAP?

A

informs functions of proteins and what they are doing
reveals if they move
no recovery means no movement

44
Q

what is function of lamin A and B?

A

essential for structure of nucleus
forms under inner nuclear envelope
disassembles and reassembles nucleus during mitosis
important in gene regulation

45
Q

retrograde transport?

A

proteins in golgi go back to ER

46
Q

anterogrande transport

A

protein from ER to Golgi

47
Q

where are vldl formed?

A

vldl made in liver

48
Q

wheres ldl particle formed?

A

made in liver

49
Q

differences between chylomicrons and VLDL?

A

chylomicrons are made in intestine and vldl made in liver

chylomicrons have smaller Apo-48

50
Q

what is C-reactive protien (CRP)?

A

biomarker of atherosclerosis and cardiovascular disease

51
Q

what is the outcome of anti-PCSK9 antibody?

A

increased LDLR in cell surface which binds and degrades LDL particles and LDLR recycles to the surface

52
Q

how is excess cholesterol stored as ?

A

stored in cholesterol esters in lipid droplets in the cytosol

53
Q

N linked domain required for?

A

LDL binding

54
Q

what causes familial hypercholesterolemia? (FH)

A

mutation in the LDL receptor (aka apoB-100/apoE receptor)

55
Q

where is Hdl made?

A

in liver and transfer apoCII/E to VLDL

mature HDL re-acqu8ire apoCII/E from liver

56
Q

what are ldl?

A

derived from vldl that no longer have apoCII and E

57
Q

what are apolipoproteins

A

allowing lipoprotein particles access to specific sites for the delivery, acceptance, or modification of lipids

58
Q

function of lipoprotein lipase?

A

to deliver cholesterol to peripheral tissues

59
Q

pathway of chylomicrons?

A

intestine directed pathway of lipid transport

60
Q

vldl and ldl pathway?

A

liver directed pathway of lipid transport

61
Q

what does hypercolesterolemia and lipidemia result in?

A

coronary heart disease

62
Q

function of lipid raft?

A

compartmentalize cellular processes

63
Q

what is the starting point for synthesizing cholesterol?

A

2 acetyl CoA (post translational modification)

64
Q

where is HMG CoA reductase located in?

A

ER

65
Q

HMG CoA metabolizes into ?

A

mevalonic acid

66
Q

how much ATP is required to synthesize 1 cholesterol molecule?

A

a lot. (very ATP expensive).
18 ATP/cholesterol molecule
14 NADPH/cholesterol

67
Q

is cholesterol a source of energy?

A

No because it takes a lot of energy to make.

68
Q

what is SCAP?

A

SREBP Cleavage Activating Protein that binds to SREBP

69
Q

what is protease 1 and protease 2 responsible for?

A

its for the 2 step cleavage of SREBP

cell bio (9 decks)

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