Cholesterol synthesis Flashcards

(64 cards)

1
Q

Cholesterol is a precursor to?

A
Bile salts (for far emulsification)
Steroid hormones
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2
Q

What is Cholesterol an essential component of?

A

Cell membranes

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3
Q

Where is cholesterol located on the cell membrane?

A

between membrane fatty acid chains

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4
Q

What tendency does cholesterol have in the membrane?

A

to cluster

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5
Q

Where is the highest concentration of cholesterol and what’s the %?

A

plasma membrane (25% of total lipid content)

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6
Q

Where is cholesterol least likely to be found?

A

inner mitochondrial matrix (virtually absent)

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7
Q

How does cholesterol reduce fluidity?

A

by forming loose cross-links

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8
Q

When does cholesterol increase rigidity?

A

when next to saturated LCFA

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9
Q

What percentage of cholesterol circulates as free form?

A

30%

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10
Q

What are most esterified LCFA’s attached to?

A

hydroxyl group

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11
Q

When fat and cholesterol combine what do they form?

A

A cholesterol ester is formed

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12
Q

What form of cholesterol is more hydrophobic?

A

Esterified cholesterol

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13
Q

Where is esterified cholesterol not found?

A

in membranes

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14
Q

What transports esterified cholesterol?

A

lipoproteins

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15
Q

Where is esterified cholesterol solubilized?

A

in Bile (by bile salts and phospholipids)

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16
Q

What is an ester?

A

Any organic molecule produced by combining an acid with an alcohol

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17
Q

Can most human cells make cholesterol?

A

yes

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18
Q

Where is the primary site of cholesterol synthesis?

A

Liver

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19
Q

What extrahepatic sites for cholesterol synthesis are there?

A

Adrenal cortex
Intestine
Reproductive tissue (ovaries, testes, placenta)
(AIR)

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20
Q

What is the location in the cell for cholesterol synthesis?

A

cytosol

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21
Q

Where are all of the reactions of cholesterol synthesis at?

A

cytosol

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22
Q

Where are some of the enzymes for cholesterol synthesis attached to?

A

endoplasmic reticulum

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23
Q

Where are the carbon atoms (Acetyl Coa) coming from for cholesterol synthesis?

A

Oxidation of LCFA’s (OHOT)
Oxidation of pyruvate (Glycolysis)
Oxidation of ketogenic amino acids

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24
Q

Where does the reducing power for cholesterol synthesis come from?

A

NADPH (Pentose Phosphate pathway)

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25
Where is the energy for cholesterol synthesis coming from?
ATP breakdown | Thioester cleavage
26
What does one mole of cholesterol require?
18 moles of Acetyl CoA 16 moles of NADPH 36 moles of ATP
27
What is the rate-limiting, key regulatory step of cholesterol synthesis?
HMG CoA reductase
28
What does HMG CoA reductase create?
mevalonate
29
What is the first unique compound in cholesterol synthesis?
Mevalonate
30
Is HMG CoA reductase reversible or irreversible?
irreversible
31
When is HMG CoA active?
when non-phosphorylated
32
When is HMG CoA inactive?
when phosphorylated
33
What is HMG CoA?
a membrane protein of the ER that projects into the cytosol to create mevalonate
34
What is the pathway to cholesterol from Acetyl CoA?
``` Acetyl CoA Acetoacetyl CoA HMG CoA Mevalonate Squalene Cholesterol ```
35
Where are primary bile acids made?
liver
36
Where are primary bile acids excreted to?
duodenum
37
Where are secondary bile acids made?
intestine
38
How are secondary bile acids made in the intestine?
Bacterial enzymes act on the primary bile salts (acids)
39
Why is it important for Bile salts/acids to be polar and non-polar?
Emulsification in intestine
40
What is the only primary mechanism for cholesterol excretion?
cholesterol excretion by bile salts
41
What kind of nucleus do bile acids have?
saturated steroid nucleus
42
What kind of position do all hydroxyl groups have on bile acids?
alpha configuration
43
What can bile salts/acids do at physiological pH?
they ionize and occur as sodium or potassium salts
44
What are the primary bile salts?
glycocholic acid glycochenodeoxycholic acid taurocholic acid taurochenodeoxycholic acid
45
What are the secondarybile salts?
deoxycholic acid | lithocholic acid
46
What is the precursor to all steroid hormones?
Pregnenolone
47
Please recite the Cholesterol Synthesis Story.
Eat cholesterol Muscle and liver are full of energy and glycogen Glucokinase pushes glycolysis forward (liver) Prep step runs Start the Krebs cycle Citrate is kicked out (high energy charge) Citrate Lyase gives back the acetyl CoA make fat and cholesterol
48
For sterol dependent HMG CoA reductase what does Low sterol levels in cells do?
stimulates HMG CoA Reductase (increased cholesterol synthesis)
49
For sterol dependent HMG CoA reductase what does high sterol levels in cells do?
down regulates cholesterol synthesis
50
For sterol accelerated HMG CoA reductase what does high sterol levels in cells do?
start to degrade HMG CoA reductase
51
What inhibits sterol independent HMG CoA reductase?
Phosphorylation from AMP-activated protein kinase
52
What hormones upregulate HMG CoA reductase?
Insulin and thyroxine
53
what hormones downregulate HMG CoA reductase?
Glucagon and glucocorticoids
54
What are the competitive inhibitors of HMG CoA reductase?
Statins
55
Can the ring structure of cholesterol be metabolized in humans?
no
56
How is cholesterol excreted?
Turned into bile salts and excreted in feces | Some modified by bacteria in the colon for excretion
57
What are the ingredients for cholesterol?
Acetyl Coa, NADPH, and ATP | Same as the ingredients for building a fatty acid
58
What is the main enzyme in cholesterol synthesis?
HMG CoA reductase
59
All biles salts end in what?
"cholic acid" or "cholate"
60
Is there degradation of cholesterol?
No
61
What is cholesterol synthesis stimulated by?
ATP NADPH Insulin Fructose
62
What is cholesterol synthesis inhibited by?
ADP AMP NADP Glucagon
63
What is the pathway from Mevalonate to Steroid hormones?
1.Mevalonate 2. Squalene 3. Cholesterol 4. Steroid hormones (steps 1-3 are the same for Bile salts)
64
What is the pathway from Melavonate to Bile salts?
1.Mevalonate 2. Squalene 3. Cholesterol 4. Bile salts (from mevalonate to cholesterol, the pathway is the same for steroid hormones)