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Biochem Take 2. > Cholesterol Synthesis. > Flashcards

Cholesterol Synthesis. Flashcards

1
Q

Is free cholesterol found in the plasma membrane?

A

Yes.

In both layers.

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2
Q

Why is free cholesterol found in the plasma membrane?

A

It maintains membrane fluidity at different temperatures.

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3
Q

How is cholesterol usually obtained by the body?

A

It is normally taken in via the diet.

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4
Q

Can the liver synthesise cholesterol?

A

Yes.

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5
Q

Cholesterol is a key component of what digestive tool?

A

Bile acids.

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6
Q

Can the brain synthesise cholesterol?

A

Yes.

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7
Q

Why will the brain synthesise cholesterol?

A

As it cannot cross the blood brain barrier.

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8
Q

Cholesterol is used to form what hormones?

A

Cortisol - in the adrenal cortex.

Testosterone - testes.

Estradiol - ovaries.

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9
Q

Can the liver synthesise hormones?

A

No.

But it can alter them.

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10
Q

Where does cholesterol synthesis take place?

A

In the cytoplasm and smooth ER of liver cells.

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11
Q

Where in the liver cell is the enzyme HMG-CoA reductase found?

A

In the smooth ER.

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12
Q

What 3 things will regulate cholesterol synthesis?

A

Substrate availability and energy status.

Serum, insulin and glucagon ratios.

Pre existing cholesterol.

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13
Q

Why will ATP levels always be kept high in the liver?

A

So it can maintain essential processes such as gluconeogenesis

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14
Q

What hormone will activate cholesterol synthesis?

A

Insulin.

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15
Q

What is the building block that is used for cholesterol synthesis?

A

ACoA.

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16
Q

Can the ACoA that forms fatty acids be used for cholesterol synthesis?

A

Yes.

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17
Q

What is the regulatory step of cholesterol synthesis?

A

The 3rd step, where 3 molecules of ACoA are bonded together to make mevalonate.

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18
Q

What enzyme is responsible for forming mevalonate?

A

HMG CoA reductase.

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19
Q

Other than forming mevalonate, what other job can HMG CoA reductase do?

A

It can form ketone bodies.

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20
Q

How many carbons does cholesterol have?

A

27.

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21
Q

What happens in step 1 of cholesterol synthesis?

A

2 molecules of cytoplasmic ACoA are joined together to form acetoacetyl-CoA.

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22
Q

What enzyme will join 2 ACoAs to make acetoacetyl CoA?

A

Cytosolic thiolase.

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23
Q

How many carbons does acetoacetyl CoA have?

A

4.

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24
Q

How many carbons does ACoA have?

A

2.

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25
Q

What happens in step 2 of cholesterol synthesis?

A

Another molecule of ACoA is added to acetoacetyl-CoA to form HMG-CoA.

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26
Q

What enzyme will form HMG-CoA in step 2 of cholesterol synthesis?

A

HMG-CoA synthase.

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27
Q

What is the regulated step of cholesterol synthesis?

A

Step 3.

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28
Q

What happens in step 3 of cholesterol synthesis?

A

HMG-CoA is reduced to mevalonate and 2 NADP+ molecules are reduced.

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29
Q

What enzymes will statins try to inhibit?

A

HMG-CoA reductase.

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30
Q

Is the formation of mevalonate irreversible?

A

Yes.

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31
Q

What is the enzyme used, substrate, product and coenzymes used in step 3 of cholesterol synthesis?

A

Enzyme used. HMG-CoA reductase.

Substrate. HMG CoA.

Product. Mevalonate.

Coenzymes. 2 NADP+.

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32
Q

How many carbons does mevalonate have?

A

6.

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33
Q

What happens in step 4 of cholesterol synthesis?

A

Mevalonate is converted into 3-isopentenyl pyrophosphate in 3 reactions.

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34
Q

Does the conversion of mevalonate to 3-isopentenyl pyrophosphate use any energy?

A

Yes.

Each of the 3 reactions uses 1 ATP.

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35
Q

How many carbons are lost when mevalonate is converted to 3-isopentenyl pyrophosphate?

A

1.

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36
Q

What happens in step 5 of cholesterol synthesis?

A

3-isopentenyl pyrophosphate is isomerised to form dimethylallyl pyrophosphate.

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37
Q

What happens in step 6 of cholesterol synthesis?

A

A 3-isopentenyl pyrophosphate molecule is added to dimethylallyl pyrophsophate.

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38
Q

What is the name of the product formed in step 6 of glycolysis, when a 3-isopentenyl pyrophosphate molecule is added to dimethylallyl pyrophsophate.

A

Geranyl pyrophosphate.

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39
Q

How many carbons does geranyl pyrophosphate have?

A

10.

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40
Q

What happens in step 7 of cholesterol synthesis, after gernayl pyrophosphate has been formed?

A

Another 3-isopentenyl pyrophosphate is added to geranyl pyrophosphate.

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41
Q

What is formed in step 7 of cholesterol synthesis when 3-isopentenyl pyrophosphate is added to geranyl pyrophosphate?

A

Farnesyl pyrophosphate molecule.

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42
Q

What happens in step 8 of cholesterol synthesis, after farnesyl pyrophosphate has been formed?

A

2 farnesyl pyrophosphate molecules are combined to make a 30 carbon molecule.

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43
Q

What is the 30 carbon molecule called that is formed by the 2 farnesyl pyrophosphate molecules in step 8?

A

Squalene.

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44
Q

How many carbons does squalene have?

A

30.

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45
Q

How many carbons does farnesyl pyrophosphate have?

A

15.

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46
Q

What happens in step 9 of cholesterol synthesis?

A

The synthesis of lanosterol.

47
Q

The formation of cholesterol form squalene requires a large amount of which molecule?

A

NADPH.

48
Q

The absence of what part of cholesterol synthesis will result in microcephaly and death?

A

The synthesis of the double bond in ring B.

49
Q

What is the quick 1st step of cholesterol synthesis?

A

2+2 = 4.

2 ACoA + 2 ACoA = 4 carbons.

50
Q

What is the quick 2nd step of cholesterol synthesis?

A

4+2 = 6.

Acetoacetyl CoA + ACoA = mevalonate (6 carbons).

51
Q

What is the quick 3rd step of cholesterol synthesis?

A

6-1 = 5.

Mevalonate is reduced to 3-isopentyl pyrophosphate = -1 carbon.

52
Q

What is the quick 4th step of cholesterol synthesis?

A

5+5 = 10.

Dimethylallyl pyrophsophate + 3-isopentyl pyrophosphate is joined together to form geranyl pyrophosphate.

53
Q

What is the quick 5th step of cholesterol synthesis?

A

10+5 = 15.

Dimethylallyl pyrophsophate + 3-isopentyl pyrophosphate joins to form farnesyl pyrophosphate.

54
Q

What is the quick 6th step of cholesterol synthesis?

A

15+15 = 30.

2 farnesyl pyrophosphates are joined together to make squalene.

55
Q

What is the quick 7th step of cholesterol synthesis?

A

30-3 = 27.

Squalene is reduced to form cholesterol.

56
Q

Other than forming cholesterol, what can the 10 carbon geranyl groups be used for?

A

They can be used to anchor proteins in the cell membrane.

57
Q

Other than forming cholesterol, what can the 15 carbon farnesyl groups be used for?

A

They are an important component in specific proteins.

58
Q

Other than forming cholesterol, what can the 15 carbon farnesyl PP groups be used for?

A

They can be used to synthesise COQ.

They can also be used to synthesise dolichol-PP which is needed for the N-glycosylation of proteins.

59
Q

What is the non hormonal activation of HMG CoA reductase?

A

Substrate availability. (HMG CoA in the cytoplasm).

60
Q

What is the non hormonal inhibition of HMG CoA reductase?

A

Low energy.

Phosphorylation.

High cholesterol.

61
Q

Why is HMG CoA reductase inhibited by low energy levels?

A

Because the liver needs to keep as much energy as it can for essential processes.

62
Q

How is HMG CoA reductase inhibited when energy levels are low?

A

An AMP kinase will phosphorylate HMG CoA reductase.

63
Q

How will high cytosolic levels of cholesterol inhibit HMG CoA reductase?

A

By stopping the transcription of HMG CoA reductase and by degrading the present enzyme.

64
Q

What binding protein does not reach the nucleus when cholesterol inhibits HMG CoA reductase?

A

The SRE binding protein.

65
Q

What does the SRE binding protein usually do when cholesterol levels are low?

A

It will be released from ER or nuclear membrane to bind to ACoA reductase and start cholesterol synthesis.

66
Q

Which hormone will activate HMG CoA reductase?

A

Insulin.

67
Q

How will insulin activate HMG CoA reductase?

A

It will de-phosphorylate the enzyme.

It will up-regulate the enzyme.

68
Q

Which hormone will inhibit HMG CoA reductase?

A

Glucagon.

69
Q

How will glucagon inhibit HMG CoA reductase?

A

It will phosphorylate the enzyme via the protein kinase A pathway and an AMP kinase kinase.

70
Q

What will AMP kinase do?

A

It will phosphorylate HMG CoA reductase.

71
Q

When is AMP kinase active?

A

When it is phosphorylated.

72
Q

When is AMP kinase inactive?

A

When it is de-phosphorylated.

73
Q

Is both cholesterol and FA synthesis activated by insulin?

A

Yes.

74
Q

Is both cholesterol and FA synthesis inhibited by glucagon?

A

Yes.

75
Q

Where does the majority of cholesterol and FA synthesis occur?

A

In the cytoplasm of the liver.

76
Q

What is the substrate for cholesterol synthesis?

A

HMG CoA.

77
Q

What is the substrate for FA synthesis?

A

ACoA.

78
Q

What is the regulated enzyme in cholesterol synthesis?

A

HMG CoA reductase.

79
Q

What is the regulated enzyme in FA synthesis?

A

Acetyl CoA carboxylase.

80
Q

Will ACoA carboxylase be inhibited by phosphorylation?

A

Yes.

81
Q

Will HMG CoA reductase be inhibited by phosphorylation?

A

Yes.

82
Q

What molecule will non hormonally inhibit ACoA carboxylase?

A

Cholesterol.

83
Q

What molecule will non hormonally inhibit HMG-CoA reductase?

A

Palmitate

84
Q

The state of fatty acids is highly dependent on what?

A

Temperature.

85
Q

The melting point of a fatty acid will increase with what?

A

Chain length.

Lack of double bonds.

86
Q

How does cholesterol alter cell membranes at low temperatures?

A

Cholesterol will increase membrane fluidity by separating them to prevent close packing.

87
Q

How does cholesterol alter cell membranes at high temperatures?

A

The steroid ring of cholesterol will decrease the fluid nature of the fatty acids and stabilise the membrane.

88
Q

The outer layer of the plasma membrane is mainly composed of what 4 substances?

A

Phosphatidylcholine.

Sphingomyelin.

Glycosphivnglipids.

Phosphoditdylethanoline.

89
Q

What is the difference between sphingomyelin and phosphatidylcholine?

A

They have the same polar head, but different backbones.

90
Q

What is the backbone of sphingomyelin?

A

The phosphosphingolipid ceramide N acyl sphingosine.

91
Q

Where is sphingomyelin found?

A

In the membranes of RBCs.

It is a major structural phospholipid in myelin in nerve fibres.

92
Q

The inner layer of the plasma membrane is mainly composed of what 5 substances?

A

Phosphatidylethanolamine.

Phosphatidylcholine.

Phosphatidylserine.

Phosphatidylinositol.

PIP2.

93
Q

What charge does phosphatidylserine have?

A

A negative charge.

94
Q

What does phosphatidylinositol contain?

A

Arachidonic acid.

95
Q

What can phosphatidylinositol be used to form?

A

PIP-2.

96
Q

Where are glycoproteins found on the cell membrane?

A

On the outer layer of the membrane.

97
Q

Where in the cell is cardiolipin found?

A

In the inner mitochondrial membrane.

98
Q

Polar lipids in humans are divided into what 2 categories?

A

Phosphate containing.

Sugar Containing.

99
Q

What are the characteristics of phosphate containing lipids?

A

Most have a glycerol backbone and are known as phospholipids.

100
Q

What are the characteristics of sugar containing lipids?

A

Most contain a sphingosine backbone and are known as glycolipids.

101
Q

Which lipid is neither a phospholipid or a glycolipid?

A

Sphingomyelin is a phospholipid and a glycolipid.

102
Q

Why is sphingomyelin a glycolipid and a phospholipid?

A

As it contains a phosphate group which is bound to a sphingosine backbone.

103
Q

Where are glycolipids found?

A

In the brain.

In the peripheral nervous tissue.

In the myelin sheaf.

104
Q

Describe cerebrosides?

A

These have 1 sugar and 1 ceramide.

105
Q

Describe globosides?

A

These are formed from cerebrosides and contain more sugars.

106
Q

Define sulphatides?

A

These are globosides that contain sulphated galactosyl residues.

107
Q

Describe globosides?

A

These are globosides that have an added N-acetyl-neuraminic-acid.

108
Q

Where are globosides usually found?

A

In the central nervous system.

109
Q

What is the structure of a glycerophospholipid?

A

They have a glycerol backbone that is bound to a phosphatidic acid and 2 fatty acids.

110
Q

Are glycerophospholipids polar or non polar?

A

Polar.

111
Q

What can make up the phosphatidic acid in glycerophospholipids?

A

Choline.

Ethanolamine.

Serine.

Inositol.

112
Q

What is the structure of a sphingolipid?

A

These contain phosphocoline bound to ceramide.

113
Q

What is the structure of a glycosphingolipids?

A

They an N-acyl sphingosine (ceramide) and either a cerebroside, globoside, sulphatide or gangliotide.

114
Q

Where are sphingolipids often found?

A

In RBC membranes and in the myelin of nerve fibres.

Biochem Take 2. (24 decks)

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