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LECOM PBL S1 E2 > Pharm 19 and biochem 34 > Flashcards

Pharm 19 and biochem 34 Flashcards

1
Q

__________ are macromolecular aggregates that transport triglycerides and cholesterol in the blood

A

Lipoproteins

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2
Q

What is the largest and least dense class of lipoproteins

A

Chylomicrons

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3
Q

What are the smallest and most dense lipoprotein class

A

HDLs

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4
Q

What lipoproteins contains the highest proportion of proteins

A

HDLs

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5
Q

_____ are amphipathic proteins that intercalate into the surface coat of lipoproteins

A

Apolipoproteins

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6
Q

What determines the metabolic fate of the lipoprotein

A

Apolipoprotein content

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7
Q

What apoprotein is a ligand for the LDL receptor

A

ApoB100

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8
Q

What apolipoproteins does HDL serve as a reservoir for

A

The exchangeable apolipoproteins in the plasma, including apoAI, apoCII and apoE

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9
Q

What is the primary function of apoB-containing lipoproteins

A

Deliver fatty acids in the form of triglycerides to muscle tissue for use in ATP biogenesis and to adipose tissue for storage

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10
Q

Where are chylomicrons formed

A

Intestine

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11
Q

Where are VLDL particles formed

A

Liver

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12
Q

What is a key regulatory event that differentiates chylomicron metabolism from VLDL metabolism

A

Editing of apoB mRNA

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13
Q

What is apoB editing complex-1 (apobec-1) expressed within

A

Enterocytes but not hepatocytes

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14
Q

What constitutes the catalytic subunit of the apoB editing complex

A

Apobec-1

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15
Q

What results when the there is deamination of the cytosine of the apoB mRNA molecule to uridine

A

Nucleotide is converted from a glutamine to a premature stop codon

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16
Q

Lipid absorption into the enterocytes of the duodenum and jejunum is facilitated mainly by _______

A

Micelles

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17
Q

What are long-chain fatty acids and monoglycerides taken up departed into the enterocyte and re-esterified to form triglycerides by

A

DGAT

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18
Q

What are medium-chain fatty acids absorbed directly into

A

Portal blood

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19
Q

How do dietary and biliary cholesterol from micelles enter the enterocyte

A

Via a protein channel named Niemann-pick C1-like protein (NPC1L1)

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20
Q

What protein is involved in the immediate pumping back into the lumen of cholesterol (some of it)

A

ABCG5/8

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21
Q

What do hepatocytes synthesize triglycerides in response to?

A

Increased free fatty acid flux to the liver

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22
Q

What in hepatocytes lipidates apoB100 to form nascent VLDL particles

A

MTP

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23
Q

Where is apoB48 Synthesized

A

Intestine

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24
Q

Where is apoB100 synthesized

A

Liver

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25
Q

What must chylomicrons and VLDL acquire before they can bind to LPL

A

ApoCII

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26
Q

What occurs when chylomicrons and VLDL can bind to LPL

A

Hydrolyzing of triglycerides from the core of the lipoprotein

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27
Q

What controls the rate of lipolysis of chylomicron and VLDL triglycerides

A

ApoCIII, which is an inhibitor of LPL activity

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28
Q

What are apoAI and apoCII transferred to HDL in exchange for?

A

ApoE

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29
Q

What apolipoprotein serves as a high-affinity ligand for receptor-mediated clearance of the particles

A

ApoE

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30
Q

What does cholesterol activate (enzyme) in order to increase esterification and storage of cholesterol in the cell

A

ACAT

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31
Q

What does PCSK9 do

A

It is a secreted protein that binds the LDL receptor, promoting its degradation

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32
Q

Where does HDL formation mainly occur

A

Liver

33
Q

What does ABCA1 do

A

Incorporates a small amount of membrane phospholipid and unesterified cholesterol into the apoAI molecule

34
Q

What does PLTP do

A

Transfers phospholipids from the surface coat of apoB-containing remnant particles to the surface coat of HDL

35
Q

What 2. Transporters are mainly involved in mediating phospholipid and cholesterol secretion

A

ABCB4 (for phospholipids) and ABCG5/8 for cholesterol

36
Q

What is another name for statins

A

HMG-CoA reductase inhibitors

37
Q

What does SREBP2 do

A

Transcription factor that upregulates expression of the gene encoding the LDL receptor

38
Q

What does increased level of SREBP2 cause

A

Increased uptake of plasma LDL, and consequently decreases plasma LDL cholesterol concentration

39
Q

What is the least potent statin

A

Fluvastatin

40
Q

What statins are metabolized by p450 SA4

A

Lovastatin, simvastatin, and atorvastatin

41
Q

Who should nice acid sequestrants be used with caution with

A

In patients with hypertriglyceridemia

42
Q

Who are inhibitors of bile acid absorption mainly used for

A

Treatment of hypercholesterolemia in young and in patients form whom statins alone did not provide sufficient plasma LDL reduction

43
Q

Why are plant sterols useful

A

They have similar molecular structure to cholesterol but are more hydrophobic (displace cholesterol from micelles, increasing the excretion of cholesterol in the stool)

44
Q

How does ezetimibe decrease cholesterol transport from micelles into enterocytes

A

By selectively inhibiting cholesterol uptake through a brush border protein, NPC1L1

45
Q

What do fibrates do

A

Bind to and activates PPARalpha

46
Q

What happens to PPARalpha once it binds with fibrate

A

Heterodimerizes with retinoids X receptor (RXR)

47
Q

What is the end result of fibrates

A

Results in numerous changes in lipid metabolism that act collectively to decrease plasma triglyceride levels and increase plasma HDl

48
Q

What are fibrates indicated for the use of

A

Treatment of hypertriglyceridemia as well as hypertriglyceridemia with low HDL

49
Q

What does niacin do

A

Decreases plasma LDL-cholesterol and triglyceride concentrations and increases HDL cholesterol

50
Q

What is the major adverse affect of niacin

A

Cutaneous flushing and prutitis

51
Q

What is the most effective agent available for raising HDL

A

Niacin

52
Q

what protein is required for reverse cholesterol transport and the biogenesis of HDL

A

ABCA1

53
Q

what NPC1L1 believed to do

A

transport cholesterol into cells via an absorptive endocytotic mechanism, involving the protein clathrin

54
Q

what do SREBPs specifically do

A

specifically enhance transcription of the HMG-CoA reductase gene by binding to the sterol-regulatory element (SRE) upstream of the gene

55
Q

what is cholesterol ester production in the liver catalyzed by

A

acyl-CoA-cholesterol acyl transferase (ACAT)

56
Q

what does ACAT catalyze

A

the transfer of a fatty acid from coenzyme A to the hydroxyl group on carbon 3 of cholesterol

57
Q

what is the rate limiting step of the synthesis of bile salts

A

7-alpha-hydroxylase

58
Q

what are the primary bile salts

A

cholic acid and chenodeoxycholic acid

59
Q

what are some secondary bile salts

A

deoxycholic acid and lithocholic acid

60
Q

what apoprotein activates LPL

A

apoCII

61
Q

what does apoAI do

A

activates LCAT; structural component of HDL

62
Q

what apoprotein may regulate transfer of apoproteins from HDL to other lipoprotein particles

A

apoAII

63
Q

what apoprotein may be involved in assembly of HDL and chylomicrons

A

ApoAIV

64
Q

what is the role of ApoB48

A

assembly and secretion of chylomicrons from small bowel

65
Q

what is the role of apoB100

A

VLDL assembly and secretion; structural protein of VLDL, IDL, and LDL; ligand for LDL receptor

66
Q

what apoprotein may inhibit hepatic uptake of chylomicron and VLDL remnants

A

ApoCI

67
Q

what apoprotein is the cofactor activator of LDL

A

apoCII

68
Q

what is the apoprotein that is the ligand for binding of several lipoproteins to the LDL receptor, to the LRP

A

apoE

69
Q

what is the function of chylomicron remnants

A

return dietary lipids to the liver

70
Q

what is the function of VLDL

A

deliver endogenous lipids

71
Q

what is the function of IDL

A

return endogenous lipids to the liver; precursor of LDL

72
Q

what is the role of LDL

A

deliver cholesterol to the cells

73
Q

what does LCAT do

A

catalyzes the transfer of fatty acid from the 2-position of lecithin (phosphatidylcholine) in the phospholipid shell of the particle to the 3-hydroxyl group of cholesterol, forming a cholesterol ester

74
Q

describe region one of the LDL receptor

A

LDL-binding domain

75
Q

describe region 2 of the LDL receptor

A

epidermal growth factor-like domain; transducin-beta-subunit-like domain

76
Q

describe region 3 of the LDL receptor

A

N-linked oligosaccharide domain

77
Q

describe region 4 of the LDL receptor

A

O-linked oligosaccharide domain

78
Q

describe region 4 of the LDL receptor

A

transmembrane domain

79
Q

describe region 6 of the LDL receptor

A

intracellular (Cytostolic) domain

LECOM PBL S1 E2 (2 decks)

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