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Cholesterol Synthesis Flashcards

1
Q

What is the rate limiting step of cholesterol synthesis?

A

HMG CoA reductase

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2
Q

What substrate is the substrate and product needed for HMG CoA reductase?

A

Substrate: 3-hydroxy-3-methyl-glutaryl Coa
Product: Mevalonate

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3
Q

What is directly formed after mevalonate?

A

isopentenyl disphosphate and dimethylallyl diphosphate

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4
Q

The 5 carbon isoprene units in cholesterol synthesis form what directly after?

A

Geranyl diphosphate (C10)

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5
Q

What is the product after geranyl diphosphate (C10)?

A

Farnesyl diphosphate

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6
Q

What is formed after farnesyl diphosphate?

A
  • Dolichol phosphate (synthesis of glycoproteins),
  • farnesylated proteins (Ras) (signal transduction),
  • geranylgeranyl disphosphate to yield either ubiquinone (CoQ10 for oxidative phosphorylation) or geranylgeranylated proteins (Rho for signal transduction)
  • Squalene to eventually yield bile salts, steroid hromones, vit D, membrane structure
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7
Q

Geranylgeranyl disphosphate can form what products?

A

ubiquinone (Coenzyme Q10) and gernaylgeranylated proteins (Rho)

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8
Q

What enzymes are needed in the formation of HMA CoA synthase, HMG CoA reductase, and LDL receptor?

A

SCAP and SREBP-2

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9
Q

What is the role of SCAP in synthesis of synthesis of HMGCoA synthase, reductase, and LDL receptor?

A

Critical for movement of SREBP to golgi as it contains sterol sensing domain and traps SCAP in ER

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10
Q

What is the role of SREBP in synthesis of synthesis of HMGCoA synthase, reductase, and LDL receptor?

A

SREBP-2 is a sterol regulatory element binding protein that helps produce these enzymes

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11
Q

What downregulates production of HMGCoA synthase, reductase, and LDL receptor?

A

Cholesterol which then produce oxysterols. Oxysterols act directly on SCAP

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12
Q

What is the key enzyme and rate limiting step in production of bile salts from cholesterol?

A

7a-hydroxylase

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13
Q

What are the 2 issues with diets high in saturated fat?

A
  1. Saturated fats reduce membrane fluidity thus leading to creased clustering and uptake by LDLR, increasing LDL levels in blood
  2. Diets high in saturated fats inhibit the Acetyl-CoA acetyl transferase reaction used to esterify cholesterol
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14
Q

What is the main and primary intermediate formed in Bile Acid/salt formation?

A

Cholic acid

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15
Q

What are products of further metabolism of cholic acid in intestine?

A

Deoxycholic acid and lithocholic acid

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16
Q

What are the functions of bile acids?

A
  1. Emulsify fats so necessary for fat digestion
  2. Facilitate absorption of fat soluble vitamins
  3. Only significant mechanism for eliminating cholesterol from body
  4. Prevent precipitation of free cholesterol out of solution inthe gall bladder
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17
Q

What is the order of lipoproteins in highest concentration of triglycerides to lowest?

A

Chylomicrons, VLDL, LDL, HDL

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18
Q

What is the order of highest cholesterol esterified to lowest?

A

LDL, HDL, VLDL, Chylomicrons

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19
Q

What are the apoproteins for chylomicrons?

A

B48, E, A, C

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20
Q

What are the apoproteins for VLDL?

A

B100, E, C

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21
Q

What are the apoproteins for LDL?

A

B100

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22
Q

What are the apoproteins for HDL?

A

A, C, E

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23
Q

What is the role of Apo C?

A

Activator of Lipoprotein lipase (LPL)

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24
Q

What is the role of Apo A?

A

Binding of HDL to peripheral tissues and an activator of LCAT (Cholesterol ester)

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25
What is the role of Apo B-100?
Involved in binding of LDL to the LDL receptor
26
What is the role of Apo E?
Involved in binding of chylomicron, VLDL, and HDL remnants to the liver after their TGs have been removed
27
What is the role of Apo E plus Apo B-100?
Involved in binding of IDL to the liver
28
What is the role of LPL?
- Located on endothelial surface of blood capillaries adjacent to tissues capable of using fats (adipose tissue) - Required for TG hydrolysis from chylomicrons and VLDL - Activated by Apo C in those lipoproteins - Activated by insulin - Insulin activation involves secretion and transport to endothelial surface
29
What is the role of hepatic lipase?
- Located on endothelial surface of blood capillaries adjacent to liver - Hydrolyzes TGs in final stage of conversion of VLDL, and IDL to LDL - Also involved in removal of cholesterol during final stages of HDL metabolism - not regulated
30
Lipoprotein lipase is dependent on which apoprotein?
Apo C
31
Removal of triglyericdes from lipoproteins yields __?
remnant particles
32
Remnant particles are targeted to __ for __
Liver for destruction
33
True or false: Cholesterol can diffuse among lipoproteins and between lipoproteins and tissue
True
34
Chylomicrons are originally synthesized containing which apoproteins (before pick)
ApoA and ApoB48
35
Chylomicrons pick up apoproteins ___ from ___
Apo C, Apo E, CE from HDL
36
After the triglyceride is removed, which apoproteins are transferred back to HDL?
Apo A and Apo C
37
Nascent VLDL is synthesized in the liver originally with which apoproteins?
CE, C, and ApoB100
38
VLDL obtains which apoproteins from HDL?
Apo E and Apo C
39
After VLDL interacts with LPL and hydrolyzes TGs to FFAs in muscle and adipose tissue, which apoprotein is exchanged with HDL?
VLDL picks up CE and transfers ApoC to HDL
40
What products can VLDL turn into?
Remnant (IDL) and LDL
41
What are the apoproteins on remnant lipoprotein (IDL)
Apo E and Apo B100
42
What are the apoproteins on LDL?
LDL picks up CE from HDL but also contains B100
43
What are the two types of IDL?
Rich in ApoE (50%) and little ApoE
44
LDL loses __ to peripheral tissues by __ diffusion via binding to ___
cholesterol; passive; apoB receptor
45
How is LDL formed?
After VLDL loses TG to hepatic lipase, it is converted to LDL. In the process, LDL picks up CE from HDL
46
What is the half life of LDL?
days
47
What is the half life of IDL?
Hours
48
What is the role of LCAT? (Lecithin-cholesterol acyltransferase)
- Catalyzes esterification of cholesterol associated with HDL thus trapping cholesterol in the interior of HDL particle.
49
What acitvates LCAT?
ApoA
50
What is the role of CETP? (Cholesterol ester transfer protein)
Transfers the cholesterol esters from HDL to VLDL, IDL, and LDL. Main mechanism for delivery of cholesterol to the liver.
51
CETP works with another protein called Phospholipid transfer protein (PLTP). What is the role of PLTP?
Transfers TGs and phospholipids from those particles to HDL
52
What is the role of apoprotein A?
- Facilitates binding of HDL particles to ApoA receptors on peripheral tissues. - Activates a transport protein called ABC1 - Activates LCAT reaction
53
What is the role of ABC1?
It is responsible for efflux of 50% of the cholesterol from peripheral tissue (other 50% effluxes by passive diffusion)
54
Nascent HDL is originally synthesized with which apoproteins?
ApoA and ApoE
55
Nascent HDL picks up which apoproteins and from which lipoproteins?
ApoA and Apo C picked up from VLDL remnants and chylomicron remnants
56
HDL donates which apoproteins to chylomicrons?
ApoC and Apo E
57
Nascent HDL binds to which receptor on peripheral tissue to pick up cholesterol?
ApoA
58
HDL contains which molecule to help activate apoA and esterify cholesterol?
LCAT
59
HDL also contains __ which transfers __ to LDL, VLDL remnants (IDL) and chylomicron remnants?
CETP; CE
60
HDL binds to which receptor on the liver, in which it is internalized and destroyed?
apoE
61
VLDL, IDL, and LDL bind to which receptors on liver in which they are internalized and destroyed?
ApoB and ApoE
62
What is an issue with diets low in fiber?
Fiber binds bile acids in the intestine, which decreases enterohepatic circulation, promoting excretion of cholesterol. This leads to higher level of cholesterol in the cell, down regulation of LDLR, and upregulation of plasma LDL
63
What is an issue with diets high in cholesterol?
Diets high in cholesterol will lead to a lot of cholesterol being taken up by the cell, leading to down regulation of LDLR

Cardiology (18 decks)

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