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Biochemistry II Final 181 > Cholesterol synthesis > Flashcards

Cholesterol synthesis Flashcards

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
Q

Where is the energy for cholesterol synthesis coming from?

A

ATP breakdown

Thioester cleavage

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26
Q

What does one mole of cholesterol require?

A

18 moles of Acetyl CoA
16 moles of NADPH
36 moles of ATP

27
Q

What is the rate-limiting, key regulatory step of cholesterol synthesis?

A

HMG CoA reductase

28
Q

What does HMG CoA reductase create?

A

mevalonate

29
Q

What is the first unique compound in cholesterol synthesis?

A

Mevalonate

30
Q

Is HMG CoA reductase reversible or irreversible?

A

irreversible

31
Q

When is HMG CoA active?

A

when non-phosphorylated

32
Q

When is HMG CoA inactive?

A

when phosphorylated

33
Q

What is HMG CoA?

A

a membrane protein of the ER that projects into the cytosol to create mevalonate

34
Q

What is the pathway to cholesterol from Acetyl CoA?

A 
Acetyl CoA
Acetoacetyl CoA
HMG CoA
Mevalonate
Squalene
Cholesterol
35
Q

Where are primary bile acids made?

A

liver

36
Q

Where are primary bile acids excreted to?

A

duodenum

37
Q

Where are secondary bile acids made?

A

intestine

38
Q

How are secondary bile acids made in the intestine?

A

Bacterial enzymes act on the primary bile salts (acids)

39
Q

Why is it important for Bile salts/acids to be polar and non-polar?

A

Emulsification in intestine

40
Q

What is the only primary mechanism for cholesterol excretion?

A

cholesterol excretion by bile salts

41
Q

What kind of nucleus do bile acids have?

A

saturated steroid nucleus

42
Q

What kind of position do all hydroxyl groups have on bile acids?

A

alpha configuration

43
Q

What can bile salts/acids do at physiological pH?

A

they ionize and occur as sodium or potassium salts

44
Q

What are the primary bile salts?

A

glycocholic acid
glycochenodeoxycholic acid
taurocholic acid
taurochenodeoxycholic acid

45
Q

What are the secondarybile salts?

A

deoxycholic acid

lithocholic acid

46
Q

What is the precursor to all steroid hormones?

A

Pregnenolone

47
Q

Please recite the Cholesterol Synthesis Story.

A

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
Q

For sterol dependent HMG CoA reductase what does Low sterol levels in cells do?

A

stimulates HMG CoA Reductase (increased cholesterol synthesis)

49
Q

For sterol dependent HMG CoA reductase what does high sterol levels in cells do?

A

down regulates cholesterol synthesis

50
Q

For sterol accelerated HMG CoA reductase what does high sterol levels in cells do?

A

start to degrade HMG CoA reductase

51
Q

What inhibits sterol independent HMG CoA reductase?

A

Phosphorylation from AMP-activated protein kinase

52
Q

What hormones upregulate HMG CoA reductase?

A

Insulin and thyroxine

53
Q

what hormones downregulate HMG CoA reductase?

A

Glucagon and glucocorticoids

54
Q

What are the competitive inhibitors of HMG CoA reductase?

A

Statins

55
Q

Can the ring structure of cholesterol be metabolized in humans?

A

no

56
Q

How is cholesterol excreted?

A

Turned into bile salts and excreted in feces

Some modified by bacteria in the colon for excretion

57
Q

What are the ingredients for cholesterol?

A

Acetyl Coa, NADPH, and ATP

Same as the ingredients for building a fatty acid

58
Q

What is the main enzyme in cholesterol synthesis?

A

HMG CoA reductase

59
Q

All biles salts end in what?

A

“cholic acid” or “cholate”

60
Q

Is there degradation of cholesterol?

A

No

61
Q

What is cholesterol synthesis stimulated by?

A

ATP
NADPH
Insulin
Fructose

62
Q

What is cholesterol synthesis inhibited by?

A

ADP
AMP
NADP
Glucagon

63
Q

What is the pathway from Mevalonate to Steroid hormones?

A

1.Mevalonate
2. Squalene
3. Cholesterol
4. Steroid hormones
(steps 1-3 are the same for Bile salts)

64
Q

What is the pathway from Melavonate to Bile salts?

A

1.Mevalonate
2. Squalene
3. Cholesterol
4. Bile salts
(from mevalonate to cholesterol, the pathway is the same for steroid hormones)

Biochemistry II Final 181 (3 decks)

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