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Cardiology-Exam 2 > Cholesterol Biosynthesis > Flashcards

Cholesterol Biosynthesis Flashcards

1
Q

Example of bad cholesterol

A

LDL (Low density lipoprotein)

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2
Q

Composition of a cholesterol molecule (2 parts)

A 
Steroid nucleus (4 fused rings)
Hydrocarbon tail
(possible long chain FA at C3 if esterified)
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3
Q

What makes a cholesterol ester

A

A long chain FA added to the A ring at Carbon #3

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4
Q

Cholesterol esters are highly (hydrophilic/phobic)

A

Hydrophobic

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5
Q

% of cholesterols that are esterified

A

70%

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6
Q

_________ are in the interior of the lipoproteins, while ________ is on the surface

A

Cholesterol esters; free cholesterol

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7
Q

Roles of cholesterol

A 
Membrane composition
Signaling
Bile acids
Steroid hormones
Vitamin D
Embryo formation
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8
Q

Greatest synthetic site of cholesterol

A

Liver (80%)

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9
Q

Rate-limiting step in cholesterol synthesis

A

HMG CoA reductase

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10
Q

HMG CoA reductase activity is inhibited by ____________

A

free, non-esterified cholesterol

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11
Q

Insulin (inhibits/stimulates) gene expression of HMG CoA reductase

A

Stimulates (promotes storage as cholesterol)

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12
Q

Class of drugs that are structural analogs of HMG CoA; bind and competitively inhibit enzyme

A

Statin drugs

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13
Q

HMG CoA reductase sits on what membrane?

A

Endoplasmic Reticulum

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14
Q

Cholesterol derivative involved in oxidative phosphorylation

A

Coenzyme Q10

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15
Q

Cholesterol derivative involved in synthesis of glycoproteins

A

Dolichol phosphate

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16
Q

Cholesterol derivatives involved in signal transduction

A

Rho and Ras

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17
Q

In cholesterol-depleted cells, this protein binds to SREBPs and mediates their transport from the ER to the Golgi apparatus. The SREBPs are then proteolytically cleaved and stimulate sterol biosynthesis.

A

SCAP

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18
Q

High cholesterol can create _______, which can inhibit SCAP and prevent cholesterol biosynthesis via HMG CoA

A

Oxysterols

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19
Q

LDL receptors are down-regulated by…

A

free cholesterol

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20
Q

Role of LDL

A

provide cholesterol to peripheral tissue

return it to the liver

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21
Q

LDL receptors

A

Apo B100

Apo E

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22
Q

Enzyme that esterifies cholesterols for storage

A

ACAT

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23
Q

A diet high in saturated fats can have what enzymatic effects?

A 
Inhibit ACAT (can only use unsaturated)
Reduced LDL
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24
Q

A diet low in fiber can have what enzymatic effects?

A

Fiber binds bile acids in intestine, increasing clearance.

Low fiber means increased bile acids circulating, inhibiting 7a hydroxylase

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25
Rate limiting step in bile acid synthesis
7a-hydroxylation
26
Primary bile acids made by liver
Cholic acid | Chenodeoxycholic acids
27
Why are bile acids good emulsifiers
have polar and nonpolar portions
28
Only significant mechanism for eliminating cholesterol from the body
Conversion into bile
29
What regulates 7a-hydroxylase activity?
``` cholesterol (activates) bile acids (inhibited) ```
30
% of bile acids that are reabsorbed in enterohepatic circulation
99%
31
Drug that inhibits cholesterol absorption in small intestine
Etzetimibe
32
Drug that binds bile acid in intestine
Cholestyramine
33
Transport "vehicle" for TGs, PLs, cholesterol and CEs in conjuction with apoproteins
Lipoproteins
34
Cholesterol esters are located in the (core/surface) of lipoproteins
Core
35
Pattern of lipoproteins in order of least to most dense
Chylomicrons-->VLDL-->LDL--->HDL
36
The more dense the lipoprotein, the (bigger/smaller) and (more/less) triglycerides
Smaller; less TGs
37
What hormone helps with production and unloading of cholesterol at tissues
Insulin
38
Apoprotein that activates lipoprotein lipase (LPL); offloading at peripheral tissue
Apo C
39
Apoprotein involved in binding of HDL to peripheral tissues and activates LCAT (forms esters); also activates ABC1, which is responsible for 50% of cholesterol efflux from peripheral tissue
Apo A
40
Apoproteins on chylomicrons after formation in intestine
Apo A
41
Apoprotein involved in binding of LDL to liver receptors
Apo B-100
42
Apoprotein involved in binding chylomicrons, VLDL and HDL to liver after TGs have been removed
Apo E
43
Apoproteins involved in binding of IDL to the liver
Apo E plus Apo B-100
44
Enzyme located on endothelial surfaces of capillaries (especially adipose tissue); required for TG hydrolysis from chylomicrons and VLDL; activated by apo C and insulin
Lipoprotein Lipase
45
Enzyme located on endothelial surfaces of capillaries (liver); used in conversion of VLDL and IDL to LDL
Hepatic Lipase
46
______ is a lipoprotein that is an important acceptor and donor of apoproteins
HDL
47
HDL gives what to chylomicrons so they can deposit TG and be recycled
Apo C Apo E Cholesterol esters
48
Half-time of exogenous pathway of chylomicrons
very short (minutes)
49
After VLDL has TG removed and apoC lost to HDL, it becomes...
IDL (remnant particle)
50
Two classes of IDL
rich in apoE: bind to liver and is destroyed (rapid= hours) | little apoE: converted to LDL, loses cholesterol to tissues and binds to liver (slowly= days)
51
lipoprotein that transports cholesterol from peripheral tissue to liver
HDL
52
enzyme that catalyzes esterification of cholesterol associated with HDL; activated by Apo A
LCAT
53
protein that transfers the cholesterol esters from HDL to VLDL, IDL, and LDL; represents main mechanism of cholesterol delivery to liver
Cholesterol Ester Transfer Protein (CETP)
54
protein that transfers TGs and phospholipids from VLDL, LDL and IDL to HDL
Phospholipid Transfer protein (PLTP)
55
transport protein responsible for 50% of cholesterol efflux from peripheral tissues to HDL; activated by Apo A
ABC1
56
Nascent HDL (empty lipid bilayer) made by the liver has what apoproteins
Apo A and Apo E
57
What are the intermediates of cholesterol?
1. geranyl diphosphate (C10) | 2. Farnesyl diphosphate (C15)
58
What can farnesyl diphosphate turn into?
geranylgeranyl diphosphate (C20)
59
What can geranylgeranyl diphosphate become that is involved in oxidative phosphorylation?
Coenzyme Q10 (ubiquinone)
60
What can geranylgeranyl diphosphate become that is involved in signal transduction?
geranylgeranlyated proteins (Rho)
61
What can farnesyl diphosphate become that is involved in signal transduction?
farnesylated proteins (Ras)
62
What can farnesyl diphosphate become that is involved in synthesis of complex glycoproteins?
dolichol phosphate
63
How many carbons does mevalonate have?
C6
64
How many carbons does cholesterol have?
C27
65
What enzyme metabolizes HMGCoA during fasting state for energy?
HMGCoA Lyase (in mitochondria) produces acetyl coa & acetoacetate
66
What is SREBP-2 and SCAP?
SREBP-2 is a transcription factor that regulates the gene expression of HMGCoA synthase, reductase, and LDLR. SCAP is a protein that binds and transports SREBP-2 from ER to golgi.
67
What happens to SREBP-2 in Golgi?
SREBP-2 gets cleaved by protease and gets activated. Then it moves to the nucleus to regulate HMGCoA synthase, reductase, and LDLR at the transcription level.
68
What up-regulates HMGCoA reductase expression?
Insulin (during fed state)
69
What down-regulates HMGCoA reductase expression?
Intracellular (free, non-esterified) cholesterol by producing oxysterols that inhibit SCAP --> inhibition of SREBP-2 transcription factor.
70
A diet high in saturated fats can have what effects?
1. Inhibit ACAT (it only uses PUFAs to esterify cholesterol) 2. Increase plasma LDL (SF reduces membrane fluidity since it has no double bond --> reduced clustering and uptake of LDLR)
71
Primary bile acids made by liver are
1. Cholic acid (has glycine) | 2. Chenodeoxycholic acid
72
What is the rate-limiting step of bile acid synthesis?
7a-hydroxylation
73
What are the bile acids/salts made when primary bile acids get further metabolized in the intestine?
1. Deoxycholic acid | 2. Lithocholic acid
74
What are the primary functions of bile acids (3)?
1. fat digestion 2. absorption of fat-soluble vitamins 3. prevent the precipitation of free cholesterol out of solution in the gall bladder
75
What enzyme is located on the endothelial surface of blood capillaries adjacent to tissues capable of using fats and is required for TG hydrolysis?
Lipoprotein lipase (LPL) *activated by insulin
76
What enzyme is located on the endothelial surface of blood capillaries adjacent to liver and is required for TG hydrolysis?
Hepatic lipase (HL) *NOT regulated by insulin
77
what apoprotein is needed to activate LPL?
apoprotein C
78
what apoprotein is needed for chylomicron to bind to the liver?
Apo E and ApoB-100

Cardiology-Exam 2 (23 decks)

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