Fatty Acid Oxidation and Ketone Bodies. Flashcards

1
Q

What provides the necessary energy for gluconeogenesis?

A

Beta oxidation of fatty acids.

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2
Q

Fatty acid oxidation is carried out when the body is in what state?

A

The fasting state.

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3
Q

What will the beta oxidation of fats provide that can be used as a gluconeogenic regulator?

A

NADH.

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4
Q

What do high levels of NADH inhibit?

A

The PDH step and the TCA cycle of glucose metabolism.

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5
Q

How can the NADH and FADH2 that are made in fatty acid oxidation be used to generate energy?

A

They can enter the ETC.

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6
Q

How will the bodies metabolism alter if the starvation period lasts longer than 3 days?

A

Glycogen stores will be empty and the liver will be involved in ketone body synthesis.

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7
Q

The beta oxidation of fatty acids is said to resemble is said to resemble what shape?

A

A spiral.

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8
Q

What does fatty acid oxidation start with?

A

A fatty acyl CoA.

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9
Q

What does fatty acid oxidation finish with?

A

A fatty acyl CoA that is 2 carbons shorter than the original fatty acyl CoA.

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10
Q

What is generated in each of the 4 steps of the FA spiral?

A
  1. Fatty acyl (n carbons) CoA.
  2. Enoyl CoA + FADH2.
  3. Beta hydroxyacyl CoA.
  4. Beta ketoacyl CoA + NADH.
  5. Fatty acyl (n-2) CoA + ACoA.
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11
Q

What is the order of the 4 enzymes that are used in the FA spiral?

A

Acyl CoA dehydrogenase.

Hydratase + H2O.

Hydroxyacyl CoA dehydrogenase.

HSCoA + thiolase.

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12
Q

What happens in step 1 of the FA spiral?

A

Fatty acyl CoA reacts with an enzyme to make enoyl CoA and FADH2.

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13
Q

What is the enzyme substrate and product of step 1 of fatty acid synthesis?

A

Enzyme used. Acyl CoA dehydrogenase.

Substrate. Fatty acyl CoA.

Product. Enoyl CoA and FADH2.

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14
Q

What prosthetic group is used by acyl CoA dehydrogenase?

A

FAD.

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15
Q

Why is the fatty acid said to be n carbons long?

A

Because the fatty acids can be of varying length.

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16
Q

What happens to FADH2 that is formed by acyl CoA dehydrogenase?

A

It can enter the ETC.

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17
Q

What is the alpha carbon of fatty acyl CoA?

A

Carbon 2.

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18
Q

What is the beta carbon of fatty acyl CoA?

A

Carbon 3.

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19
Q

Does the same acyl CoA dehydrogenase work on all fatty acids?

A

No.

Different ACoA dehydrogenases will work on the different chains with respect to their length.

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20
Q

What happens in step 2 of fatty acid oxidation, once enoyl CoA has been formed?

A

Enoyl CoA will react with a hydratase and H2O to produce beta hydroxyacyl CoA.

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21
Q

What is the enzyme substrate and product of step 2 of fatty acid synthesis?

A

Enzyme used. Enoyl CoA hydratase + H2O.

Substrate. Enoyl CoA.

Product. Beta hydroxyacyl CoA.

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22
Q

What happens in step 3 of fatty acid oxidation, once hydroxyacyl CoA has been formed?

A

Beta hydroxyacyl CoA is oxidised to beta ketoacyl CoA and an NADH is produced.

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23
Q

What happens to the NADH formed in step 3 of fatty acid oxidation?

A

It can enter the ETC to generate ATP.

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24
Q

How many carbonyl groups will ketoacyl CoA have?

A

2.

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25
Q

What is the enzyme substrate and product of step 3 of fatty acid synthesis?

A

Enzyme used. Hydroxyacyl CoA dehydrogenase.

Substrate. Beta hydroxyacyl CoA.

Product. Beta ketoacyl CoA.

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26
Q

What is the prosthetic group that is used by hydroxyacyl CoA dehydrogenase?

A

NAD+.

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27
Q

What happens in step 4 of fatty acid oxidation, once beta keto acyl CoA has been formed?

A

Beta ketoacyl CoA is converted to fatty acyl (n-2) CoA and free CoA.

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28
Q

How many carbons is beta keto acyl CoA reduced by in step 4 of fatty acid synthesis?

A

2.

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29
Q

What process converts keto acyl CoA to fatty acyl CoA

A

Thiolytical cleavage

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30
Q

What replaces the ACoA that is cleaved from beta keto acyl CoA reduced by in step 4 of fatty acid synthesis?

A

CoASH.

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31
Q

What happens to the fatty acyl CoA that is formed in step 4 of fatty acid synthesis?

A

It will be re-entered at step 1.

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32
Q

How much energy can be produced from 1 cycle of fatty acid oxidation?

A

1 FADH2 and 1 NADH = 5 ATP.

1 ACoA = 12 ATPs in the TCA.

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33
Q

What is the cellular location of fatty acid synthesis and fatty acid oxidation?

A

FA synthesis. Cytosol.

FA degradation. Mitochondria.

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34
Q

How is ACoA used in fatty acid synthesis and fatty acid oxidation?

A

FA synthesis. ACoA is used as the substrate.

FA degradation. ACoA is the product.

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35
Q

What coenzymes are used in fatty acid synthesis and fatty acid oxidation?

A

FA synthesis. Biotin and NADPH.

FA degradation. FAD and NAD+.

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36
Q

What activates fatty acid synthesis?

A

Cytosolic ACoA.

Allosterically activated by citrate.

De-phosphorylation.

Induction by insulin.

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37
Q

What activates fatty acid oxidation?

A

High levels of free fatty acids.

Active carnitine shuttle.

38
Q

What inhibits fatty acid synthesis?

A

Alloscterically activated by palmitoyl CoA.

Phosphorylation by AMP kinase.

Glucagon and epinephrine.

39
Q

What inhibits fatty acid oxidation?

A

Malonyl CoA.

High ATP.

High NADH.

40
Q

How will fatty acid synthesis inhibit the carnitine shuttle?

A

By producing malonyl CoA in the cytosol.

41
Q

What is the carnitine shuttle needed for in fatty acid oxidation?

A

To transport of long chain fatty acids into the mitochondria.

42
Q

What are unsaturated fatty acids?

A

Fatty acids with double bonds.

43
Q

What percentage of fatty acids in humans are unsaturated?

A

Around 50%.

44
Q

Where are unsaturated fatty acids degraded?

A

In the mitochondria.

45
Q

Is there any difference between the degradation of fatty acids and unsaturated fatty acids?

A

Yes.

The degradation of unsaturated fatty acids requires 2 more enzymes.

46
Q

What are the 2 extra enzymes that are needed to degrade unsaturated fatty acids?

A

An isomerase and a reductase.

47
Q

What kind of fatty acids will not be totally degraded by fatty acid oxidation?

A

Fatty acid chains with odd numbers.

48
Q

What happens to fatty acids with odd numbers?

A

They are degraded to a propionyl CoA which will enter the TCA cycle as succinyl CoA.

49
Q

Can fatty acids with very long chains be degraded in the mitochondria?

A

No.

They have to be broken down in the peroxisomes.

50
Q

What happens to the very long chain fatty acids in the peroxisomes?

A

They will be broken down to long chain fatty acids and transported to the mitochondria.

51
Q

What does the breakdown of very long chain fatty acids to long chain fatty acids generate?

A

Hydrogen peroxide which is used by the catalase enzyme to detoxify molecules.

52
Q

Where are branched chain fatty acids degraded?

A

In the peroxisomes.

53
Q

What is the alpha oxidation of fatty acids?

A

It is the oxidation of branched chain fatty acids as the oxidation starts at the alpha carbon.

54
Q

What kind of fatty acids are branched?

A

The fatty acids that we get from dairy products.

55
Q

What do the fatty acids from dairy products contain?

A

Phytanic acid which is a 20C branched chain fatty acid.

56
Q

What fatty acids are degraded in the mitochondria?

A

Unsaturated, long, medium and short chain fatty acids.

57
Q

What fatty acids are degraded in the peroxisomes?

A

Very long and branched chain fatty acids.

58
Q

What is the equation for the degradation of palmitoyl CoA?

A

Palmitoyl CoA + 23 O2 + 129 Pi + 129 ADP = 131 ATP + 16 CO2 + 39 H2O + free CoA.

59
Q

How many ATPs are needed to break down palmitate?

A

2.

60
Q

What is the net gain of ATP from the oxidation of palmitate?

A

129 ATP.

61
Q

What is the gross gain of ATP from the oxidation of palmitate?

A

131 ATP.

62
Q

The oxidation of palmitoyl CoA generates how much ATP?

A

131 ATP.

63
Q

The oxidation of palmitate generates how much ATP?

A

129 ATP.

64
Q

How many electrons are required to reduce 1 O2 to 2 H2O?

A

4.

65
Q

What is the only organ that can form ketone bodies?

A

The liver.

66
Q

What tissues can use ketone bodies for fuel?

A

Almost all tissues except the liver.

67
Q

When are ketone bodies formed?

A

In the fasting state.

68
Q

What are the 2 ketone bodies that are formed in the liver?

A

Acetoacetate and 3-hydroxybuterate.

69
Q

What happens once ketone bodies are formed in the liver?

A

They are released into the blood and will travel to various tissues.

70
Q

Will malonyl CoA inhibit the carnitine shuttle during fasting?

A

No.

71
Q

In what state will there be an accumulation of fatty acids in the cytoplasm of liver cells?

A

in the fasting state.

72
Q

Why does the liver make ketone bodies?

A

To get rid of excess ACoA.

73
Q

Where does ketone body synthesis take place?

A

In the mitochondria of the liver in the fasting state.

74
Q

What happens in step 1 of ketone body synthesis?

A

Acetoacetyl CoA must be formed.

75
Q

What are the 2 ways that Acetoacetyl CoA can be formed in ketone body synthesis?

A

Acetoacetyl CoA that has already been formed is not degraded.

2 ACoA molecules are joined together by thiloase.

76
Q

What happens in step 2 of ketone body synthesis once acetoacetyl CoA has been formed?

A

The CoA is cleaved from acetoacetyl CoA to form acetoacetate.

77
Q

Can acetoacetyl CoA cross the inner mitochondrial membrane?

A

No.

78
Q

What does acetoacetyl CoA need to be cleaved to so that it can cross the inner mitochondrial membrane?

A

Acetoacetate.

79
Q

How is acetoacetate formed from acetoacetyl CoA?

A

HMGCoA synthase to add another CoA to make HMG CoA.

80
Q

Why will ketone synthesis only take place in the liver?

A

Because HMGCoA synthase is only found in the liver.

81
Q

What happens in step 3 of ketone body synthesis, once acetoacetyl CoA has been formed?

A

HMG CoA lyase cleaves HMG CoA to form acetyl CoA and free acetoacetate which is the first ketone body.

82
Q

What happens once acetoacetate is formed in step 3 of ketone body synthesis?

A

It can enter the blood where it will be spontaneously degraded to acetone which is exhaled.

83
Q

What happens in step 3 of ketone body synthesis, if acetoacetate does not enter the blood?

A

The liver will use NADH to make the much more stable 3-hydroxybuterate.

84
Q

Is ATP needed to activate a ketone body?

A

No.

85
Q

What happens when 3-hydroxybuterate enters a muscle cell?

A

3-hydroxybuterate is oxidised to make an NADH and acetoacetate.

Thiophorase takes an ACoA and uses it to make acetoacetyl CoA.

This gives 2 ACoA molecules that can be used for the TCA cycle.

86
Q

Where does thiophorase get ACoA from when 3-hydroxybuterate has been oxidised in the muscles?

A

From succinyl CoA in the TCA cycle.

87
Q

Why can the liver not use ketone bodies for energy?

A

It lacks the enzyme thiophorase.

88
Q

What are blood glucose levels after 3 days of starvation?

A

3.8 mM and they will not change.

89
Q

What happens to fatty acid levels in the blood during starvation?

A

They will increase.

90
Q

What happens to acetoacetate levels in the blood during starvation?

A

They will increase, but the unstable acteoacetate will be reduced to acetone.

91
Q

What happens to hydroxybuterate levels in the blood during starvation?

A

They will increase to around 6mM.

92
Q

If 2 more carbons are added to palmitate, how many extra ATPs can be generated?

A

17.