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Block 3 Week 2 Dani > G. Blomquist Cholesterol and Bile Salt Biosynthesis > Flashcards

G. Blomquist Cholesterol and Bile Salt Biosynthesis Flashcards

1
Q

What are the roles of cholesterol?

A

to make membranes
a precursor to bile salts/acids
precursor to sex hormones
precursor to vitamin D

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2
Q

What are the sex hormones that cholesterol is a precursor to?

A

progesterone, estrogen, testosterone, cortisol, aldosterone

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3
Q

gall stones can be almost all (blank)

A

cholesterol

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4
Q

Humans have about (blank) grams of cholesterol-most in membranes

A

100

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5
Q

The (Blank) group on cholesterol interacts with surfaces membrane.

A

hydroxyl

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6
Q

What makes membranes more rigid, less fluid.

A

cholesterol

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7
Q

Where is most cholesterol found?

A

membranes (especially myelin membranes)

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8
Q

How many carbons are in a cholesterol molecules?

A

27 carbons

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9
Q

Describe the strucuture of cholesterol briefly.

A 
27 carbon molecule
planar 
8 carbon side chain
four rings
methyl group on 18 and 19
hydroxyl group on position 3
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10
Q

What is in higher concentration in the blood; cholesterol or glucose?

A

cholesterol

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11
Q

Is cholesterol water soluble?

A

no!

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12
Q

Most of the cholesterol carried in the blood is in the form of (blank)

A

cholesterol ester

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13
Q

a cholesterol ester is very (blank) and is carried in the form of lipoproteins.

A

non-polar

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14
Q

(blank) is the most prominent storage from of cholesterol

A

olaic acid

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15
Q

Cholesterol plus fatty acyl-CoA=?

Via what enzyme?

A

cholesterol ester

ACAT (Acyl-CoA cholesterol acyl transferase)

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16
Q

Cholesterol plus Lechithin=?

Via what enzyme?

A

cholesterol ester

LCAT (Lecithin cholesterol acyl transferase)

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17
Q

Humans synthesize a little less than 1/2 of cholesterol we have from (blank)

A

acetyl coA

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18
Q

(blank) can come from carbohydrates (pyruvate) or fatty acids and must get to cytoplasm

A

acetyl coa

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19
Q

How can you get actyle coa across the mito membrane into the cytosol?

A

via conversion into citrate

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20
Q

How do you get oxaloacetate into the mito matrix?

A

via conversion into pyruvate

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21
Q

The mito membrane can be considered (blank)

A

impermeable

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22
Q

What are the 2 major routes to get NADPH?

A

conversion of malate into pyruvate AND

PPP

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23
Q

What is the key regulatory step of cholesterol biosynthesis?

A

HMG CoA reductase

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24
Q

How many isoprene molecules do you need to get to squalene?

A

6

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25
Q

What does squalene turn into?

A

cholesterol C27

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26
Q

What does 2 acetyl coAs turn into?

A

acetoacetyl coA :)

27
Q

Acetylacetyl coa + acetyl coa turns into what?

A

HMG CoA (via HMG-CoA synthase)

28
Q

What does HMG CoA reductase do? And what does this create?

A

it converts HMG CoA into mevalonate (an intermediate to create cholesterol)
Creates NADP+

29
Q

If we have a biosynthetic reaction dealing with reduction what are we dealing with?

A

an NADPH molecule

30
Q

In (blank) HMG-CoA goes to cholesterol

A

cytosol

31
Q

In (blank) HMG-CoA goes to ketone bodies

A

mito matrix

32
Q

What are the four ways that cholesterol production is regulated?

A

feedback inhibition
phosphorylation-dephosphorylation
control of gene expression
rate of enzyme degredation

33
Q

WHat is the most important way to regulate cholesterol production?

A

control of gene expression

34
Q

The higher the cholesterol in the diet the (blank) you make. This is why reducing cholesterol levels by diet or excercise doesn’t work for many people because your body maintains your levels

A

less

35
Q

SInce cholesterol levels are maintained, how can the body tell it has made a lot of cholesterol?

A

cholesterol has negative feedback inhibition which inhibits HMG-CoA reductase

36
Q

How does dephosphorylation or phosphorylation regulate cholesterol?

A

When AMPK gets phosphorylated it will phosphorylate HMG-CoA reductase which will make it inactive and thus inhibit cholesterol

37
Q

How can cholesterol levels be controlled by gene expression?

A

You have a sterol sensing domain on a protein called sterol receptor element binding protein, and when it senses cholesterol is low, it then cleaves the sterol receptor element binding protein to get the sterole receptor binding protein which then goes to the nucleus which binds with the SRE binding domain to increases synthesis of HMG CoA reductase

38
Q

How do statins work?

A

the working part of HMG-CoA is replicated and put onto drugs like (atorvastatin, lovastatin) that act as competitive inhibitors of HMG-CoA Reductase

39
Q

What are the 5 products of the cholesterol biosynthesis pathway?

A 
prenylated proteins
heme a dolichol ubiquinone
vitamin D
steroids
bile salts
40
Q

Where are steroids produced?

A

adrenal, gonads

41
Q

Where are bile salts produced?

A

liver

42
Q

Explain the pathway of cholesterol biosynthesis in terms of carbon numbers.

A

C4->C6->C5->C10->C15->C30 and through 21 steps you get cholesterol C27

43
Q

How many ATP’s do we need to turn Mevalonat into isopentenyl pyrophosphate or dimethallyl pyrophosphate? What is a side product of this?

A

3 ATPs

CO2

44
Q

Cholesterol has a single (blank) group.

A

OH

45
Q

C30 will turn into a cholesterol via (blank).

A

cytochrome p450s

46
Q

Turning Squalene into cholesterol involves (blank).

A

NADPH

47
Q

Major metabolic fate of cholesterol is conversion to (blank)

A

bile acids

48
Q

(blank) is present in bile acids in small amounts-it can form insoluble gall stones

A

cholesterol

49
Q

YOu can remove a gall bladder and then (blank) will go directly into small intestine

A

Bile acids

50
Q

(blank) is where cholesterol is regulated and the only place you can make bile salts

A

Liver

51
Q

(blank) is amphoteric so it can emulsify lipids

A

bile acids/salts

52
Q

What are the two pathways cholesterol can take to complete the first step in cholesterol becoming bile salts/acids?

A

classic pathway via 7-hydroxylase

acidic pathway via 27 hydroxylase

53
Q

How many different bile salts are there?

A

8

54
Q

WHat are the major four bile salts?

A

cholic acid
deoxycholic acid
chenodeoxycholic acid
lithocholic acid

55
Q

MOst bile salts have (blank) or (blank) attached

A

glycine or taurine

56
Q

Why is salt better than acids for emulsification?

A

salts have more polar regions

57
Q

Also in the (Blank), bacteria can work on bile salts and make secondary bile salts.

A

intestine

58
Q

conjugated bile acids/salts make bile acids better (blank).

A

solubilizing agents

59
Q

Pka of conjugated bile acids/salts are around (blank)
Pka of non conjugated bile acids/salts are around (blank)
pH of the duodenum is (Blank)

A

1-4
7.0
3-5

60
Q

How does cholestyramine work?

A

Normally you reabsorb you bile salts (90%) and this conserves cholesterol. Cholestyramine binds to bile salts and makes them unable to be reabsorbed and therefore excreted through the feces.
(negatively charged bile acids bind to (+) nitrogen

61
Q

How does cholestyramine work?

A

Normally you reabsorb you bile salts (90%) and this conserves cholesterol. Cholestyramine binds to bile salts and makes them unable to be reabsorbed and therefore excreted through the feces.
(negatively charged bile acids bind to (+) nitrogen

62
Q

How does cholestyramine work?

A

Normally you reabsorb you bile salts (90%) and this conserves cholesterol. Cholestyramine binds to bile salts and makes them unable to be reabsorbed and therefore excreted through the feces.
(negatively charged bile acids bind to (+) nitrogen

63
Q

WHat is enteroheptaic circulation?

A

uptake and reuse of bile acids

Block 3 Week 2 Dani (9 decks)

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