Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CPR1 Exam 1 > 24- Lipids & Lipoproteins > Flashcards

24- Lipids & Lipoproteins Flashcards

1
Q

Three Acetyl CoA (a 2-C compound) are used to generate one _________ _________ (a 5-C compound).

A

Isopentenyl Pyrophosphate (IPP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

IPP serves as the building block for the synthesis of all _________.

A

Isoprenoids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

__________ include steroids, lipid-soluble vitamins, ubiquinone, and prenyl groups that anchor proteins to plasma membrane.

A

Isoprenoids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Acetyl CoA is generated in the _________ from various pathways.

A

Mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What the pathways that can generate Acetyl CoA (in Mitochondria)?

A
    • Oxidative decarboxylation of pyruvate
    • Beta oxidation of FAs
    • Breakdown of amino acids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How is Acetyl CoA transported into the Cytoplasm from the Mitochondria?

A

Via Citrate shuttle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Six units of IPP form a tetracyclic (4-ring) ________ ________ that is the backbone of most steroids.

A

Sterane Ring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

This is an allicyclic compound made of 4 fused rings (sterane) with a molecular weight of 386 g/mol and has 27 carbons.

A

Cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the structure of Cholesterol.

A
    • Sterane ring has 17C
    • Side chain is 8 member hydrocarbon chain attached C17
    • Two methyl groups at C10 and C13
    • One double bond between C5 and C6
    • One hydroxyl group at C3
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Cholesterol is the most abundant sterol (about 0.05% of total body weight) and is a component of plasma membranes and precursor of biologically active compounds such as…

A

Bile acids and salts

Vitamin D

Steroid hormones (i.e., Progesterone, Aldosterone, Cortisol, Testosterone, and Estradiol)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

T/F. Cholesterol can be broken down a specific lyase and its components are utilized.

A

False. Cells are unable to degrade the steroid nucleus of Cholesterol.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Cholesterol must be used biochemically or excreted by the ________. Excess Cholesterol may lead to _________.

A

Liver

Atherosclerosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the recommended daily intake for Cholesterol?

A

<300 mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Daily production of Cholesterol is about _______ (mostly in liver, small intestine, adrenal cores, ovaries, testes, and skin). Daily excretion is about ________ excreted and about ________ reabsorbed.

A

1 g
5%
95%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Biosynthesis of Cholesterol is __________ proportional to dietary intake.

A

Inversely

***This means, if you eat a lot of Cholesterol then your body will make less, and if you don’t eat very much Cholesterol then your body will make more!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How many Acetyl CoA are required to make Cholesterol?

A

18

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

The synthesis of Cholesterol is broken into two Phases, which are what?

A

Phase I – Generation of IPP from Acetyl CoA

Phase II – Generation of Cholesterol from IPP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the steps in Phase I of Cholesterol synthesis?

A

1) Acetyl CoA converted to Acetoacetyl CoA
2) Acetoacetyl CoA converted to HMG CoA (Hydroxymethylglutaryl CoA) via the enzyme HMG CoA Synthase
3) HMG CoA converted to Mevalonate via HMG CoA Reductase RATE-LIMITING STEP
4) Mevalonate converted to IPP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

These drugs will target HMG CoA Reductase, not allowing HMG CoA to convert to Mevalonate, thus reducing the production of Cholesterol.

A

Statins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the steps in Phase II of Cholesterol synthesis?

A

1) IPP is converted to Squalene
2) Squalene is converters to Lanosterol
3) Lanosterol is converted to Cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

The conversion of Lanosterol to Cholesterol can be inhibited by what?

A

Anti-fungal Agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

The IPP produced at the end of Phase I is also used for Prenylated Proteins (i.e., Ras), Heme A, Dolichol, and Ubiquinone. What is important about Ubiquinone?

A

Also called CoQ10, it’s important for the ETC and the production of ATP.

***That’s why Statins can have a negative effect on ATP production because IPP isn’t made. If a person is on Statins, it’s important to make sure they’re also receiving CoQ10 supplements.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the rate-limiting step in the synthesis of Cholesterol?

A

Conversion of HMG CoA to Mevalonate via the enzyme HMG CoA Reductase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

HMG CoA Reductase is a target for the regulation of Cholesterol Synthesis. It is composed of an 8-pass transmembrane domain in the _______ and a catalytic domain in the _______ (this is where molecules bind).

A

ER

Cytosol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Inhibitors of HMG CoA Reductase, aka Statins, will fit into the pocket of the Catalytic Site. Statins work really well because they have a highly increased ________ than the natural substrate. Prevent Cardiovascular disease.

A

Affinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Statins are strong _________ _________ of HMG CoA Reductase. Km for HMG CoA is 4 uM, while the Ki for statins is 5-45 nM.

A

Competitive Inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Hypocholesterolemic (low Cholesterol) action is also due to an increase in _________ maturation which leads to transcription of LDL receptor and subsequent enhanced clearance of Cholesterol via LDL receptor mediated endocytosis.

A

SREBP (Sterol Regulatory Element Binding Protein)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Mytotoxic side effects include Statin-mediated myopathy caused by depletion of muscle levels of __________. This results in impairment of mitochondrial function. An alternative to avoid this has been to use inhibitors of Squalene synthase, called __________. This prevents the depletion of ________.

A

CoQ10 (Ubiquinone)
Squalestatins
CoQ10

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Cholesterol is esterified to Cholesterol esters by the enzyme…

A

ACAT (Acyl CoA:Cholesterol Acyltransferase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Cholesterol synthesis is regulated via effects on HMG CoA Reductase. What are these effects?

A
    • Direct Inhibition
    • Covalent Modification
    • Transcriptional Control
    • Translational Control
    • Post-translational Control
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What can HMG CoA Reductase be directly inhibited by?

A

Free FAs
Bile Acids
Oxysterols
Statins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Covalent modification can also regulate HMG CoA Reductase. This enzyme is (ACTIVE/INACTIVE) in the phosphorylated form and (ACTIVE/INACTIVE) in the dephosphorylated form.

A

Inactive

Active

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

During conditions of low energy, there is high amounts ______. This activates _______, which phosphorylates HMG CoA Reductase, and inactivates it.

A

AMP

AMPK

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

_________ activates HMG CoA Reductase by dephosphorylating it.

A

Insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

_________ inactivates HMG CoA Reductase by phosphorylating it.

A

Glucagon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

For Transcripitonal Control, transcription factors will bind to the promoter on the HMG CoA Reductase gene and increase its _______ levels.

A

mRNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Translational Control of HMG CoA Reductase is at the protein synthesis level. This enzyme is reduced by y-tocotrienol, which is a member of ________ family, and Oxylanosterols.

A

Vitamin E

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

T/F. Post-translational Control of HMG CoA Reductase is protein turnover/degradation. This is enhanced by sterols, oxysterols, and y-tocotrienol.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

HMG CoA Reductase gene has a _______ in its promoter region, and a family of transcription factors called ________ bind to the ________.

A

SRE (Sterol Regulatory Element)
SREBP (Sterol Regulatory Binding Protein)
SRE

40
Q

Inactive SREBP interacts with a protein called _______. In the presence of Cholesterol, the _______-_______ complex is retained in the ER due to binding to _______. Under these conditions, rate of transcription is low.

A

SCAP (SREBP Cleavage Activating Protein)
SREBP-SCAP
INSIG

41
Q

Low sterol promotes the release of the SREBP-SCAP complex from the ER to the _______ ________ where SREBP undergoes ________ to release the mature form of SREBP.

A

Golgi Apparatus

Proteolysis

42
Q

The mature form of SREBP will ________ and translocate to the nucleus. Once there, the SREBP binds to the ______ and promotes transcription of HMG CoA Reductase and several other genes in the Cholesterol synthesis pathway.

A

Dimerize

SRE

43
Q

These serve as vehicles for the transport of Cholesterol, Cholesterol esters, TAGs, and fat-soluble vitamins (all very hydrophobic substances with tendency to adhere to blood vessel wall).

A

Lipoproteins

44
Q

What is the structure of Lipoproteins?

A

Outer shell = Monolayer of phospholipids, free Cholesterol, and apolipoproteins

Inner core = packed with TAGs, Cholesterol, Cholesterol esters (hydrophobic)

45
Q

Lipoproteins serve as a means to transport and deliver ______ to tissues, from the intestine or liver, for use as fuel or for storage.

A

TAGs

46
Q

Lipoproteins play a key role in cholesterol _________, transporting it from site of synthesis, to sites of use, and finally to the liver for excretion.

A

Homeostasis

47
Q

__________ serve as cell targeting signals/ligands that bind to receptors to internalize lipoproteins. They also activate various enzymes involved in lipoprotein metabolism and processing.

A

Apolipoproteins

48
Q

There are 5 different types of Lipoproteins that differ based on their size, density, and composition. What are these 5 types?

A
    • Chylomicrons
    • VLDL (Very Low Density Lipoprotein)
    • IDL (Intermediate Density Lipoprotein)
    • LDL (Low Density Lipoprotein – “bad cholesterol”)
    • HDL (High Density Lipoprotein – “good cholesterol”)
49
Q

What are the sizes of the Lipoproteins from smallest to largest?

A 
HDL (smallest) 
LDL
IDL
VLDL
Chylomicron (largest)

***Relative size of plasma lipoproteins is based on their hydrated density.

50
Q

What 4 things are Lipoproteins composed of?

A

Proteins
Cholesterol
Phospholipids
TAGs

51
Q

This type of lipoprotein has the most TAGs and the least protein. They are exogenous, meaning they can only be consumed in the diet.

A

Chylomicrons

52
Q

This type of lipoprotein has the least TAGs and the most protein.

A

HDL

***From Chylomicrons going down in size, the lipoproteins will decrease in the amount of TAGs and increase in the amount of Protein.

53
Q

This type of lipoprotein has the most Cholesterol.

A

LDL

54
Q

Where are Chylomicrons synthesized? Where are the rest of the Lipoproteins synthesized?

A

Intestines

Liver

55
Q

This lipoprotein is the largest, least dense, and has high TAG content.

A

Chylomicrons

56
Q

Chylomicrons have 3 types of Apolipoproteins. What are they and what do they do?

A

ApoB-48 — Facilitates transport
ApoC-II — Activates capillary lipoprotein lipase
ApoE — Facilitates uptake into liver

57
Q

VLDL, IDL, LDL, and HDL are (ENDOGENOUS/EXOGENOUS) and made in the liver. They are packaged with TAGs and Cholesterol.

A

Endogenous

58
Q

What type of Apolipoproteins are on VLDLs and what are their functions?

A

ApoB-100 — Uptake into cells
ApoC-II — Activates capillary lipoprotein lipase
ApoE — Facilitates uptake into liver

59
Q

What type of Apolipoproteins are on IDLs and what are their functions?

A

ApoB-100 — Uptake into cells

ApoE — Facilitates uptake into liver

60
Q

What type of Apolipoproteins are on LDLs (“bad cholesterol”) and what are their functions?

A

ApoB-100 — Uptake into cells

61
Q

This type of lipoprotein is the smallest, most dense, and has high protein and phospholipid content.

A

HDL

62
Q

What type of Apolipoproteins are on HDLs and what are their functions?

A

ApoA-I — Activates enzyme that esterifies cholesterol
ApoC-II — Activates capillary lipoprotein lipase
ApoE — Facilitates uptake into liver

63
Q

Describe the steps of Chylomicron processing.

A

1) Nascent Chylomicrons are assembled with dietary lipids in the small intestine and transported through lymphatic system to bloodstream. Contain one Apolipoprotein – ApoB-48.
2) Additional Apolipoproteins are added to create mature Chylomicron. ApoC-II and ApoE are added by HDL.
3) Capillary lipoprotein lipase (activated by ApoC-II) hydrolyzes TAGs into glycerol and free FAs. ApoC-II is released back to HDL.
4) Remnants of Chylomicron are endocytosed by the liver via binding of ApoE to its receptors (on liver).

64
Q

Describe the steps of VLDL, IDL, and LDL processing.

A

1) VLDL are assembled in the liver and released into the bloodstream. They have 3 Apolipoproteins (ApoB-100, ApoC-II, and ApoE).
2) Capillary lipoprotein lipase hydrolyzes TAGs into glycerol and free FAs (via ApoC-II). ApoC-II is released (back to HDL), and IDL remains.
3) Cholesterol in IDL is delivered to the liver via binding of ApoE to IDL receptors on hepatic cells. Another outcome is the IDL lose more TAGs via hepatic lipoprotein lipase, and lose ApoE to become LDL.
4) LDL deliver their Cholesterol load to the liver and peripheral tissues via binding of ApoB-100 to LDL receptors on target cells.

65
Q

This is the major carrier of Cholesterol in the blood.

A

LDL

66
Q

Each LDL particle contains a shell of phospholipids and free Cholesterol and packed with what in its core?

A

1500 Cholesterol ester molecules

67
Q

The role of ______ is to transport Cholesterol to peripheral tissues and regulate de novo synthesis of Cholesterol at these sites.

A

LDL

68
Q

During endocytosis of LDL, in the endoscope the reduced _______ converts the receptor from the open structure into the closed structure, resulting in LDL release.

A

pH

69
Q

One class of mutations that results in familial ___________ generates LDL receptors that are unable to release the LDL cargo.

A

Hypercholesterolemia

70
Q

Describe the steps of receptor-mediated LDL endocytosis.

A

1) LDL binds to LDL receptor via ApoB-100.
2) Clathrin-coated pit forms and engulfs LDL.
3) Coated vesicle is inside the cell and becomes endosome. Vesicle and receptors are recycled.
4) Endosome transfers to lysosome to be broken down into individual Amino Acids and Cholesterol.
5) A low supply of Cholesterol will initiate HMG CoA Reductase to make more and there will be continued synthesis of LDL receptors. During an oversupply of Cholesterol, storage of Cholesterol esters occurs.

71
Q

Describe the steps of HDL processing.

A

1) Disc-shaped, nascent, lipid-poor HDL is synthesized in the liver and small intestine.
2) Nascent HDL picks up Cholesterol from peripheral tissues. Has one Apolipoprotein (ApoA-I).
3) LCAT (Lecithin Cholesterol Acyl Transferase) esterifies Cholesterol via transfer of FAs from PC onto Cholesterol. Cholesterol esters enter the HDL core, making it spherical.
4) HDL donates and receives ApoC-II and ApoE from Chylomicrons. HDL transfers Cholesterol esters to VLDL, IDL, and LDL in exchange for TAGs and phospholipids. Exchanges are facilitated by CETP (Cholesterol Ester Transfer Protein).
5) HDL delivers its Cholesterol load to the liver. VLDL, IDL, and LDL also deliver their lipids to the liver.

72
Q

High HDL Cholesterol (HDL-C) levels correlate positively with reduced risk for _________ _________ _________. Low levels however, correlate negatively with an increased risk for it.

A

Coronary Artery Disease (CAD)

73
Q

HDL is crucial for the maturation of __________ because it supplies ApoC-II and ApoE.

A

Chylomicrons

74
Q

HDL retrieves Cholesterol from other tissues in the body to return the Cholesterol to the liver for excretion as bile or in the feces. This is called ________ ________ ________. Therefore, HDL scavenges and removes _______-Cholesterol from the periphery and transports it to the liver where it can be recycles and processed.

A

Reverse Cholesterol Transport

LDL

75
Q

When Cholesterol transport fails, ___________ become foam cells and facilitate the formation of plaques. These would normally collect Cholesterol from LDL and transport it to HDL particles. The more HDL, the more readily this transport takes place and the less likely the __________ will develop into foam cells.

A

Macrophages

Macrophages

76
Q

The importance of Reverse Cholesterol Transport is illustrated by the occurrence of mutations that inactivate a Cholesterol-transport protein in endothelial cells and macrophages called __________. Under normal conditions, the ApoA-I apolipoprotein component of HDL binds to this to facilitate LDL transport.

A

ABCA1 (ATP-Binding Cassette Transporter, subfamily A1)

77
Q

Loss of ABCA1 activity of Cholesterol-transport protein results in a very rare condition called ________ _______, which is characterized by HDL deficiency, accumulation of Cholesterol in macrophages, and premature atherosclerosis.

A

Tangier Disease

78
Q

This lipoprotein is shown to have antioxidant, anti-inflammatory, antithrombotic, and NO-inducing properties. It also inhibits the oxidation of LDL and keeps the inner wall of the blood vessels healthy.

A

HDL

79
Q

Non-drug related ways HDL-C levels are increased include…

A

Weight loss
Exercise
Smoking cessation

80
Q

What lipoprotein levels are increased by Antihypercholesterolemic drugs, Fibrates, Anti-diabetic thiazolidine drugs, Estrogens, and Omega-3 FAs?

A

HDL-C

81
Q

This disease is the inability to hydrolyze TAGs in Chylomicrons and VLDL. The cause is either a deficiency in capillary Lipoprotein Lipase (LPL) or ApoC-II, which is an essential part of the LPL complex.

A

Type I Hyperlipoproteinemia

***Also called Hyperchylomicronemia

82
Q

For Type I Hyperlipoproteinemia, if it is a primary LPL deficiency then it begins in _________, and if it is an ApoC-II deficiency it begins __________. Both are autosomal recessive, and Plasma TAG levels are over 1000 mg/dL.

A

Infancy

Post-adolescence

83
Q

This disease has a creamy appearance of blood sample. Overnight storage of blood at 4˚C causes the plasma to separate into a creamy layer and a clear layer.

A

Type I Hyperlipoproteinemia

84
Q

Type I Hyperproteinemia presents with abdominal pain, acute pancreatitis, and cutaneous eruptive xanthomas. What is the treatment for this?

A

Low fat diet

***Because TAGs can’t be broken down!

85
Q

This disease is caused by defects in LDL receptors, resulting in defects in the uptake of LDL via Receptor-Mediated Endocytosis (which contributes to 75% clearance of LDL in plasma). Defective uptake causes increased Cholesterol in the blood and LDL accumulates under the endothelial cells lining the blood vessels. Autosomal dominant.

A

Type II Hyperlipoproteinemia

***Also called Hypercholesterolemia

86
Q

For Type II Hyperlipoproteinemia, due to the excess LDL it undergoes oxidation to form ________. This initiates an inflammatory response which leads to the development of cardiovascular disease such as atherosclerosis.

A

oxLDL (Oxidized LDL)

87
Q

Type II Hyperlipoproteinemia is often caused due to an impaired ability of receptors to recognize ________ on the LDL.

A

ApoB-100

88
Q

For Type II Hyperlipoproteinemia, normal Cholesterol is between 130-200 mg/dL. Since it is autosomal dominant, if a person with it is heterozygous then their Cholesterol amount is ________ mg/dL. If they’re homozygous for it then their Cholesterol is ________ mg/dL.

A

300-500

>800

89
Q

For Type II Hyperlipoproteinemia, untreated homozygotes die of _________ _________ ________ before teenager years while heterozygotes (1:500 people) may have a milder case of it and a more variable clinical outcome.

A

Coronary Artery Disease (CAD)

90
Q

For this disease, physical symptoms include xanthomas, corneal deposits in eyes, and angina pectoris.

A

Type II Hyperlipoproteinemia

91
Q

For Type II Hyperlipoproteinemia, (HOMO/HETERO)-zygous respond to diet, statins, and bile acid binding resins. (HOMO/HETERO)-zygous need LDL apheresis and liver transplantation.

A

Heterozygous

Homozygous

92
Q

_______ levels correlate positively with mortality related to cardiovascular disease. It accumulates under the endothelial cells lining blood vessels.

A

LDL-C

93
Q

Oxidative modification of LDL by ________ forms oxidized LDL (oxLDL). LDL and its oxidized form accumulate in vessel wall. This can lead to endothelial injury and dysfunction which causes further influx of LDL into the arterial wall.

A

ROS

94
Q

LDL and oxLDL in the vessel wall causes increased vascular permeability and leukocyte adhesion. oxLDL initiates an inflammatory response and are taken up by Macrophages in an unregulated manner. The Macrophages become engorged to form _______ _______.

A

Foam Cells

95
Q

Foam Cells are trapped in the walls of blood vessels to form _________. Death of foam cells, platelet adhesion, and recruitment of smooth muscle cells leads to further development of arterial _________ that eventually leads to atherosclerosis.

A

Plaques

Plaque

96
Q

Narrowing of arteries by the plaques lead to…

A

Heart attacks

CPR1 Exam 1 (22 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions