Cholesterol and Steroid Metabolism Flashcards Preview

Medical Biochemistry > Cholesterol and Steroid Metabolism > Flashcards

Flashcards in Cholesterol and Steroid Metabolism Deck (72):
1

What are the important functions of cholesterol?

1)Component of all cell membranes
2)Precursor of Bile Acids
3)Precursor of steroid hormones and Vitamin D

2

Describe the structure of cholesterol.

4 carbon ring with a hydrocarbon tail and and OH group at other end.

3

Where is the site of attachment of fatty acids in cholesterol ester?

OH group on A chain on cholesterol.

4

What is a cholesterol ester?

Cholesterol molecule with fatty acid attached to OH group end.

5

What is the main organ cholesterol metabolism takes place?

Liver
(cholesterol pool)

6

If cholesterol is completely cut out of the diet, why can high cholesterol levels persist? (in theory)

De Novo Synthesis in liver

7

What is required for cholesterol synthesis?

Acetyl CoA
NADPH
ATP

8

What is the rate limiting enzyme in cholesterol synthesis?

HMG CoA reductase

9

Where is the cell does cholesterol synthesis occur?

Occurs in the cytoplasm with enzymes in cytosol and ER

10

Too much plasma cholesterol can lead to what?

Atherosclerosis

11

Too much cholesterol secretion causes formation of what?

Gall Stones

12

What are the two phases of cholesterol synthesis?

1) synthesis of mevalonic acid (mevalonate)
2) synthesis of cholesterol from mevalonate

13

How did the Acetyl CoA used in cholesterol synthesis get there?

From citrate, broken down by ATP-citrate lyase.

14

In the first step of cholesterol synthesis, 2 Acetyl CoA are converted to what? By what enzyme?

Acetoacetyl CoA;
Thiolase

15

During the second step of cholesterol synthesis, Acetoacetyl CoA is converted to what? By what enzyme?

HMG CoA;
HMG-CoA synthase

16

HMG CoA is also known as what?

3-hydroxy-3-methylglutaryl CoA

17

HMG CoA gets converted to what? By what enzyme?

Mevalonate;
HMG CoA Reductase

18

HMG CoA reductase requires what reducing equivalents?

2 molecules of NADPH

19

In stage 2 of cholesterol synthesis, Once mevalonate is made, what is formed next?

5-pyrophosphomevalonate

20

During stage 2 of cholesterol synthesis, what is 5-pyrophosphomevalonate converted into in the 2nd step?

Isopentenyl pyrophosphate (IPP)

21

Isopentenyl pyrophosphate (IPP), besides beings converted into 3,3-dimethylallyl pyrophosphate (DPP), can also alternately be transformed into what?

Dolichol or ubiquinone

22

IPP plus DPP undergo condensation to form what?

Geranyl Pyrophosphate (GPP) -10 C

23

What gets added to Geranyl Pyrophosphate (GPP) to form Farnesyl Pyrophosphate (FPP -15 c)

IPP

24

2 Farnesyl Pyrophosphate (FPP) molecules are joined to form what?

Squalene (30C)

25

Farnesyl Pyrophosphate (FPP) (15C) an important intermediate in cholesterol synthesis, can also be a precursor for what?

Dolichol
Ubiquinone

26

Which two intermediates in cholesterol synthesis can be considered precursors for Dolichol or ubiquinone?

Farnesyl Pyrophosphate (FPP)
Isopentenyl Pyrophosphate (IPP)

27

Is Squalene cyclic or non cyclic?

Non cyclic

28

Squalene undergoes cyclization to form what?

Lanosterol (30C)

29

HMG CoA reductase is located where??

ER - cytosolic side

30

AMP kinase ________ and therefore ______ HMG CoA reductase

Phosphorylates;
Inhibits

31

How does cholesterol inhibit HMG CoA reductase?

-Allosterically
-regulating gene expression of enzyme
-promoting degradation of enzyme

32

AMP Kinase can be stimulated by what?

Glucagon or Epinephrine

33

Glucagon __________ and therefore ________ HMG CoA reductase, decreasing cholesterol synthesis.

Phosphorylates (PKA Dependent);
Inactivates

34

What are statins?

-A class of drugs that cause enzyme upregulation (reversible inhibitors of HMG CoA reductase
-long term regulation

35

Which drugs (specifically) are statins?

- Compactin
- Simvastatin (Zocov)
- Pravastatin (Pravacol)
- Lovastatin (Mevacor)

- all are structural analogs of Mevalonate.

36

Low concentrations of intracellular cholesterol stimulates what?

SREBP = sterol regulatory element binding protein
- released from ER

37

What is the function of SREBP?

Moves to a specific enhancer region (SRE= sterol responsive element) in the gene for HMG CoA reductase upregulation.

38

Why does blocking HMG CoA reductase with statins cause an upregulation of the gene?

Cholesterol usually inhibits SCAP-SREBP (SREBP cleavage activating protein). Therefore, low levels of cholesterol cause SREBP cleavage (activation) leading to upregulation of HMG CoA gene.

Usually, giving a patient a large dose of statins accounts for any new HMG CoA synthesized

39

________ concentrations of cholesterol and/or mevalonate leads to _____________ of the HMG CoA reductase enzyme.

High concentrations;
Rapid degradation (proteolysis)

40

When there is high levels of intracellular cholesterol, the ________ system in proteosomes leads to the degradation of ________

Ubiquitin;
HMG CoA Reductase

41

What are the effects of low intracellular cholesterol on HMG-CoA reductase, LDL receptors, and serum cholesterol?

- HMG CoA: upregulation
- LDL receptor: upregulation
- Increased uptake of LDL from serum
- reduction in serum cholesterol

42

Besides HMG CoA Reductase, intracellular cholesterol is a key regulator of?

- LDL receptor endocytosis
- ACAT

43

SLOS (Smith-Lemli-Optiz Syndrome) is a _________ defect of _________.

Autosomal recessive;
Cholesterol synthesis

44

SLOS is relatively common and leads to what?

- Microencephaly
- other embryonic malformations

45

What enzyme is partially deficient in SLOS? What is this enzyme needed for?

- 7-Dehydrocholesterol reductase
- needed for correct double bond formation in ring B

46

What is major mechanism of elimination of cholesterol?

Cholesterol into bile acids --> excreted in feces

47

Some cholesterol is modified by bacteria in the intestines to form what?

Cholestanol
Coprostanol

48

What forms the bulk of fecal sterols?

Cholestanol
Coprostanol
Free cholesterol

49

How do Coprostanol and Cholestanol differ?

Coprostanol: Hydrogen in B- orientation
Cholestanol: hydrogen in a-orientation

50

What are the most abundant organic components of bile?

Phosphatidylcholine (lecithin) and bile salts

51

What is another name for phosphatidylcholine?

Lecithin

52

Bile enters the _____ through the _______ or is stored in the gall bladder.

- Duodenum
- common bile duct

53

What are the primary bile acids?

Cholic acid
Chenodeoxycholic acid

54

What is the rate limiting enzyme in the synthesis of bile acids?

7-alpha-Hydroxylase

55

What is the reaction 7-alpha-Hydroxylase catalyzes?

Catalyzes the addition of an OH group to carbon 7 on cholesterol. (making it into Cholic acid)

56

How is 7-alpha-Hydroxylase regulated?

Inhibited by: Cholic acid
Stimulated by: cholesterol

57

Bile acids that are conjugated with glycine form which bile salts before leaving the liver??

-Glycocholic acid
- Glycochenodeoxycholic acid

58

Bile acids that are conjugated with taurine form which bile salts before leaving the liver??

- Taurocholic acid
- Taurochenodeoxycholic acid

59

What is more effective at solubilizing lipids than bile acids?

Bile salts like:
Glycocholic acid
Taurochenodeoxycholic acid

60

Other intestinal bacteria convert primary bile salts into ________ by removing ___________.

Secondary bile salts;
Hydroxyl groups

61

Cholic acid, under the action of intestinal flora, becomes...

Deoxycholic acid

62

Lithocholic acid, under the action of intestinal flora, becomes...

Chenodeoxycholic acid

63

What is cholelithiasis?

Bile salt deficiency

64

What are potential causes of Cholelithiasis?

-Malabsorption of bile acids from intestine
-Obstruction of the biliary tract
-Interruption of the enterohepatic circulation
- Decreased bile production (hepatic dysfunction)
- Accelerated rate of bile recycling (excessive suppression of bile synthesis)

65

What is Chenodeoxycholic acid used for?

Treatment of Cholelithiasis

66

What is another name for chenodeoxycholic acid?

Chenodiol

67

One of the four physiologically significant functions of bile acids/salts is that they facilitate ________ of dietary TAGS by acting as __________ that render fats accessible to __________.

Digestion;
emulsifying agents;
pancreatic lipases

68

One of the four physiologically significant functions of bile acids/salts is that they facilitate the intestinal absorption of_________

Fat-soluble vitamins

69

What is the significance of bile acids and phospholipids solubilizing cholesterol in the bile?

It prevents the precipitation of cholesterol in the gallbladder.

70

Migrating gallstones that obstruct the ampulla of Vater can cause what?

Acute Pancreatitis

71

Why is Pyrophosphate incorporated into cholesterol?

Without Pyrophosphate, compounds such as Squalene, Lanosterol all the downstream intermediates all the way up to cholesterol would be so hydrophobic, they would need carrier proteins to keep then soluble.

72

What is Squalene cyclized with?

NADPH and O2