Cholesterol Metabolism Flashcards Preview

Biochemistry Post Midterm > Cholesterol Metabolism > Flashcards

Flashcards in Cholesterol Metabolism Deck (63):
1

What is the most abundant sterol in the body?

cholesterol

2

What is the function of cholesterol?

1. component of all cell membranes
2. precursor of bile acids
3/ precursor of steroid hormones and Vitamin D

3

What does the synthesis of cholesterol require?

acetyl coA
NADPH
ATP

4

What is the rate limiting enzyme of cholesterol synthesis?

HMG CoA reductase

5

where does synthesis of cholesterol occur?

cytoplasm

6

where are the enzymes for synthesis of cholesterol located?

in cytosol and ER

7

what can too much plasma cholesterol lead to?

atherosclerosis

8

what can too much cholesterol secretion cause formation of?

gall stones

9

what are the 2 stages of synthesis of cholesterol ?

A. synthesis of mevalonic acid (mevalonate)
B. synthesis of cholesterol from mevalonate

10

What type of reaction is the synthesis of mevalonate?

irreversible

11

how does cholesterol regulate cholesterol biosynthesis?

cholesterol if a feedback inhibitor

12

what does AMP kinase do to HMG CoA Reductase?

phosphorylates and inhibits

13

what does glucagon do to HMG coA reductase?

phosphorylates (PKA dep.) and inactivates it - decreasing cholesterol synthesis

14

What competitevly inhibit HMG CoA reductase?

statins

15

how do statins contribute to long term regulation of cholesterol synthesis?

cause enzyme upregulation = reversible inhibitor of HMG CoA reductase

16

what does a high cholesterol diet cause?

down regulatin of HMG CoA reductase

17

What does low cholesterol levels stimulate the release of?

SREBP protein from the ER

18

what does SREBP bind to on the HMG CoA reductase gene?

sterol responsive element (SRE)

19

what does high intracellular concentrations of AMP stimulate?

AMP kinase which phosphorylates HMG -CoA and inactivates it!

20

How is HMG CoA activated?

insulin activates phosphorylation phosphatase which = dephosphorylation

21

degradation of HMG CoA reductase is controlled by what?

ubiquitin system in proteosomes

22

what does high concentration of cholesterol and/or mevalonate lead to?

rapid degradation (proteolysis) of the HMG CoA reductase enzyme

23

what does low intracellular cholesterol (with statin treatment cause)?

unreg of HMG CoA reductase
upreg of LDL receptor
inrease in uptake of LDL from serum
reduction in serum cholesterol

24

what is intracellular cholesterol a key regulator of?

HMG CoA reductase
LDL receptor endocytosis
ACAT

25

What is Smith-Lemil-Opitz Syndrome (SLOS)?

autosomal recessive cholesterol synthesis disorder
relatively common
leads to microencephaly and other embryolic malformation
surviving kids have low IQ

26

What enzyme is deficient in SLOS?

7-dehydrocholesterol reductase

27

what is 7-dehydrocholesterol reductase needed for?

the correct double bond formation in ring B

28

How is cholesterol eliminated since it cannot be degraded?

conversion of cholesterol into bile salts - excreted in feces

29

some cholesterol is modified by bacteria in the intestine to form?

cholestanol
coprostanol

30

why are cholestanol
coprostanol important

those + free cholesterol form the bulk of fecal sterols

31

what is bile made of?

organic and inorganic compounds
-phosphatidylcholine (lecithin) - org
-bile salts - org

32

What are the primary bile acids?

cholic acid
chenodeoxycholic acid

33

what is the rate limiting enzyme of the synthesis of bile acids?

7-alpha-hydroylase

34

how is 7-alpha-hydroylase inhibited?

by its own product, cholic acid (product inhibition)

35

What are bile acids conjugated with?

glycine = glycocholic acid and glycochenodeoxycholic acid

taurine = taurocholic acid
taurochenodeoxycholic acid

36

which are more effective at solubilizing lipids?

bile salts - much more than bile acids

37

What competitevly inhibit HMG CoA reductase?

statins

38

how do statins contribute to long term regulation of cholesterol synthesis?

cause enzyme upregulation = reversible inhibitor of HMG CoA reductase

39

what does a high cholesterol diet cause?

down regulatin of HMG CoA reductase

40

What does low cholesterol levels stimulate the release of?

SREBP protein from the ER

41

what does SREBP bind to on the HMG CoA reductase gene?

sterol responsive element (SRE)

42

what does high intracellular concentrations of AMP stimulate?

AMP kinase which phosphorylates HMG -CoA and inactivates it!

43

How is HMG CoA activated?

insulin activates phosphorylation phosphatase which = dephosphorylation

44

degradation of HMG CoA reductase is controlled by what?

ubiquitin system in proteosomes

45

what does high concentration of cholesterol and/or mevalonate lead to?

rapid degradation (proteolysis) of the HMG CoA reductase enzyme

46

what does low intracellular cholesterol (with statin treatment cause)?

unreg of HMG CoA reductase
upreg of LDL receptor
inrease in uptake of LDL from serum
reduction in serum cholesterol

47

what is intracellular cholesterol a key regulator of?

HMG CoA reductase
LDL receptor endocytosis
ACAT

48

What is Smith-Lemil-Opitz Syndrome (SLOS)?

autosomal recessive cholesterol synthesis disorder
relatively common
leads to microencephaly and other embryolic malformation
surviving kids have low IQ

49

What enzyme is deficient in SLOS?

7-dehydrocholesterol reductase

50

what is 7-dehydrocholesterol reductase needed for?

the correct double bond formation in ring B

51

How is cholesterol eliminated since it cannot be degraded?

conversion of cholesterol into bile salts - excreted in feces

52

some cholesterol is modified by bacteria in the intestine to form?

cholestanol
coprostanol

53

why are cholestanol
coprostanol important

those + free cholesterol form the bulk of fecal sterols

54

what is bile made of?

organic and inorganic compounds
-phosphatidylcholine (lecithin) - org
-bile salts - org

55

What are the primary bile acids?

cholic acid
chenodeoxycholic acid

56

what is the rate limiting enzyme of the synthesis of bile acids?

7-alpha-hydroylase

57

how is 7-alpha-hydroylase inhibited?

by its own product, cholic acid (product inhibition)

58

What are bile acids conjugated with?

glycine = glycocholic acid and glycochenodeoxycholic acid

taurine = taurocholic acid
taurochenodeoxycholic acid

59

which are more effective at solubilizing lipids?

bile salts - much more than bile acids

60

what can remove taurine or glycine from bile salts?

intestinal bacteria

61

how do intestinal bacteria convert primary bile salts to secondary bile salts?

by removing hydroxyl groups

62

what are the secondary bile salts?

deoxycholic acid from cholic acid
lithocholic acid from chenodeoxycholic acid

63

what will a deficiency in lecithin and or bile salts cause?

cholesterol in bile to precipiate in the gall bladder = gall stones