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2nd yr- IBMS- Fatty acids > CATABOLISM OF FATTY ACIDS > Flashcards

CATABOLISM OF FATTY ACIDS Flashcards

1
Q

What are fatty acids?

A

They are fuel molecules

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2
Q

What are fatty acids stored as?

A

They are stored as triacylglycerols

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3
Q

What are triacylglycerols?

A

They are uncharged esters of fatty acids with glycerol

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4
Q

How and when can fatty acids generate energy?

A

Fattu acids are oxidised during fasting and heavy energy to gernneate energy

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5
Q

What is the conversion of triacylglycerols to fatty acids known as?

A

Lipolysis

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6
Q

Where are triacylglycerols converted to fatty acids?

A

triacylglycerols stored in the adipose tissues are hydrolysde

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7
Q

What are triacylglycerols brocken down into?

A

4 Constituent parts:

  1. Glycerol
  2. 3 Fatty acids
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8
Q

What is eta break down of triacylglycerols dependent on?

A

Hormones

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9
Q

Name the hormones that drive the breakdown of triacylglycerols into glycerol

A

Insulin and glucagon

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10
Q

What happens to the glycerol that is Broken down from triacylglycerols

A

It is converted into Dihydroxyacetone

Phosphate (DHAP)

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11
Q

Why is DHAP important?

A

It is a Glycolytic intermediate and a Gluconeogenic intermediate

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12
Q

What happens to the fatty acids produced by the breakdown of triacylglycerols

A

They are capris by albumin to the liver or muscles to be beta oxidised

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13
Q

What happens to the free fatty acid concentration when we exercise?

A

It increases

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14
Q

Name the hormones that initiate the release of fatty acids into the blood

A

Adrenaline

Glucagon

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15
Q

Are fatty acids highly oxidised or reduced?

A

They are highly reduced

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16
Q

Give an overview of beta oxidation

A
  1. As fatty acids are highly reduced they are oxidised by NAD+ and FAD
  2. They are then metabolised to acetyl CoA
  3. Acetyl CoA is oxidised by NAD+ and FAD in the citric acid cycle
  4. NADH and FADH2 Carry electron to the electron transport chain to power ATP production
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17
Q

Where does beta oxidation take place?

A

In the mitochondria

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18
Q

Why does beta oxidation take place in the mitochondria?

A

So that acetyl CoA can easily fee into the citric acid cycle and NADH/FADH2 can easily move into eh electron transport chain

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19
Q

Can we rely on fatty acids as a sole fuel source? Why?

A

No as in the citric acid cycle we need Oxaloacetate to combine with acetyl CoA to form citrate
Fatty acids don’t produce Oxaloacetate so the citric acid cycle would stop

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20
Q

How are fatty acids activated?

A
  1. Fatty acids joins with CoA to form Acetyl CoA with the help of Acyl CoA
    synthetase
  2. This reaction costs ATP
  3. Acyl CoA then diffuses into the mitochondrial matrix
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21
Q

What does acyl CoA synthase do?

A

It joins CoA and fatty acids to form acyl CoA

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22
Q

Where does acyl CoA need to go after entering the mitochondrial membrane?

A

Into the mitochondrial

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23
Q

What difficulties does acyl CoA face when trying to enter the mitochondrial matrix

A

It is charges and the mitochondrial matrix membrane is relatively impermeable

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24
Q

How does acyl CoA enter the mitochondrial matrix ?

A
  1. Acyl CoA combines with Carnitine to form Acylcarnitine + CoA
  2. This reaction is aided by Carnitine Acyltransferase I
  3. Acylcarnitine then passes through the inner membrane via Acyl carnitine
    translocase
  4. Acylcarnitine is then broken down by the enzyme Carnitine Acyltransferase II to form Acyl CoA +Carnitine
  5. Carnitine then diffuses out through the inner membrane to again reattach to acyl CoA
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25
Q

What does Carnitine Acyltransferase I do?

A

Combines Carnitine with acyl CoA to give Acylcarnitine and CoA

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26
Q

What does Acyl carnitine

translocase do?

A

Help Acylcarnitine diffuse though the inner membrane

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27
Q

What does Carnitine Acyltransferase II do?

A

Breaks down Acylcarnitine to give acyl CoA and Carnitine

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28
Q

Name the 4 steps of beta oxidation of fatty acids

A
  1. Oxidation of Acyl CoA
  2. Hydration of trans delta enoyl CoA
  3. Oxidation of Hydroxyacyl-CoA
  4. Thiolysis of Ketoacyl-CoA
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29
Q

What is the first step of beta oxidation of fatty acids

A

Oxidation of Acyl CoA

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30
Q

What happens Acyl CoA when it enters the inner matrix

A

It is oxidised by Acyl CoA
Dehydrogenase to form trans delta enoyl CoA
This reaction produces FADH2

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31
Q

What happens to the FADH2 that os produces when acyl CoA is oxidised?

A

It goes to the electron transport chain and yields 1.5 ATPs

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32
Q

What is the second step of beta oxidation

A

Hydration of trans delta enoyl CoA

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33
Q

What happens to trans delta enoyl CoA once it has been formed?

A

It is hydrated by Enoyl-CoA

hydratase to form Hydroxyacyl-CoA

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34
Q

What does Acyl CoA

Dehydrogenase do?

A

Oxidises acyl CoA to form trans delta enoyl CoA

35
Q

What does Enoyl-CoA

hydratase

A

Hydrates delta enoyl CoA to form Hydroxyacyl-CoA

36
Q

What is the third step of bet oxidation?

A

The oxidation of Hydroxyacyl-CoA by beta-Hydroxyacyl-CoA
dehydrogenase into Ketoacyl-CoA
This reaction produces NADH which does into the electron transport chain to produce 2.5 ATPs

37
Q

What happens to the Hydroxyacyl-CoA once it has formed?

A

It is oxidised by beta-Hydroxyacyl-CoA
dehydrogenase into Ketoacyl-CoA
This reaction produces NADH which goes into the electron transport chain to produce 2.5 ATPs

38
Q

What happens to the NADH produces by the oxidation of Hydroxyacyl-CoA

A

goes into the electron transport chain to produce 2.5 ATPs

39
Q

What does beta-Hydroxyacyl-CoA

dehydrogenase do?

A

It oxidises Hydroxyacyl-CoA into Ketoacyl-CoA

40
Q

What is the fourth step of beta oxidation

A

Thiolysis of Ketoacyl-CoA

41
Q

What is Thiolysis of Ketoacyl-CoA

A

It is the breaking up of Ketoacyl-CoA

42
Q

What happen to the Ketoacyl-CoA once it has formed?

A

It undergoes Thiolysis aided by Ketoacyl-CoA
thiolase and CoA SH
It is broken down into Acyl CoA (Myristoyl CoA) and acetyl CoA

43
Q

What happens to the acetyl CoA that is produced in the Thiolysis of Ketoacyl-CoA

A

It goes into the citric acid cycle

44
Q

What happens to he acyl CoA that is produced in the Thiolysis of Ketoacyl-CoA

A

It goes back to step one of beta oxidation to be oxidised

45
Q

How many rounds of beta oxidation is required to break down Palmitoyl CoA ?into acetyl CoA

46
Q

How many carbons does Palmitoyl CoA have?

47
Q

Name the 7 carbon species that forms in the 7 rounds of beta oxidation of Palmitoyl CoA

A 
Myristoyl (14 carbons)
Lauroyl (12C)
Caproyl CoA (10C)
Capryloyl CoA (8C)
Caproicoyl? CoA (6C)
Butyryl CoA(4C)
Acetyl CoA (2C)
48
Q

How many acetyl CoA’s are yielded in the complete beta oxidation of Palmitoyl CoA

A

8 (one per each round and then 2 in the final round)

49
Q

How many NADH are yielded in the complete beta oxidation of Palmitoyl CoA

50
Q

How many FADH2 are yielded in the complete beta oxidation of Palmitoyl CoA

51
Q

What is the total true yield of ATP from the complete oxidation of Palmitate

A
  1. 8 acetyl CoA forms 8FADH2 + 24NADH
  2. total NADH= 24+7= 31
    31X2.5= 77.5 ATPs (via ECT)
  3. Total FADH2= 8+7= 15
    15x1.3= 22.5 ATPs (via ECT)
  4. Total= 77.5+22.5=100
  5. But 2 “high energy” phosphate bonds used to attach CoA during activation so true yield = 106 ATP
52
Q

What type of bond do natural unsaturated fatty acids contain?

A

cis Double bond

53
Q

Is the cis double bond metabolised by Beta oxidation enzymes?

A

no we need additional enzymes for this

54
Q

What is Palmitoleoyl CoA beta oxidised into?

A

Continuous beta oxidised to form Cis - Delta3-enoyl CoA

This is where the double bond is so beta oxidation can’t go on any longer

55
Q

How is Cis - D3-enoyl CoA further oxidised?

A

By the enzyme Cis - D3-enoyl CoA

isomerase into trans- Delta3-enoyl CoA

56
Q

What does Cis - D3-enoyl CoA isomerase do?

A

It converts Cis - D3-enoyl CoA into trans- D3-enoyl CoA

57
Q

What would happen if you were beta oxidising an odd carbon fatty acid? (Eg a 9 carbon fat acid)

A

You would yield 3 acetyl CoA after 3 rounds of beta oxidation
propionyl CoA isn’t metabolised

58
Q

Talk through the Cataboliosm of propionyl CoA

A

1,. propionyl CoA is carboxylated by Propionyl CoA Carboxylaseinto D-Methylmalonyl CoA
2. D-Methylmalonyl CoA is converted into L-Methylmalonyl CoA aided Methylmalonyl CoA
epimerase
3. L-Methylmalonyl CoA is converted in Succinyl CoA aises by Methylmalonyl CoA
mutase and Vitamin B12 coenzyme

59
Q

What does Propionyl CoA

Carboxylase do

A

Coverts propionyl CoA into Carboxylase into D-Methylmalonyl CoA

60
Q

What does Methylmalonyl CoA epimerase

A

Converts D-Methylmalonyl CoA is converted into L-Methylmalonyl CoA

61
Q

What does Vitamin B12 coenzyme do?

A

Aids in the reaction of L-Methylmalonyl CoA into Succinyl CoA

62
Q

What does Methylmalonyl CoA

mutase coenzyme do?

A

Aids in the reaction of L-Methylmalonyl CoA into Succinyl CoA

63
Q

What does B12 deficiency causes?

64
Q

What happens to the products of odd carbon fatty acid metabolism?

A

It builds up and accumulated in myelin sheaths causing neurological disorders

65
Q

How is beta oxidation regulated?

A

The conversion of TAG into fatty acid and glycerol is heavily regulated by a hormone sensitive lipase

66
Q

How is the hormone sensitive lipase that regulates TAG breakdown inactivated?

A

Insulin activates Phosphatase which phosphorylases the hormone sensitive lipase making it inactive

67
Q

How is the hormone sensitive lipase that regulates TAG breakdown activated?

A

Glucagon, Adrenaline and Noradrenaline all activates cAMP which activates protein kinase which activates hormone sensitive lipase

68
Q

What can inhibit the transport of acyl CoA into the Mitochondrial Matrix?

A

Malonyl CoA

69
Q

What do ketone bodies do?

A

They are a way of transporting liver acetyl CoA in the blood to other organs for use as fuel fro the brain, heart and muscles

70
Q

Why are ketone bodies important?

A

They are a major source of energy for the brain during starvation

71
Q

How much glucose does the brain use usually?

A

120g per day

72
Q

How much glucose does the brain use during starvation?

A

40g per day

73
Q

Where are ketone bodies transported?

A

They are easily transported across the inner mitochondrial membrane of the liver cells as well as across the blood brain barrier and cell membranes of heart and muscle tissue

74
Q

What is ketosis?

A

A normal physiological response to fasting or low carbohydrate diet

75
Q

What is Ketoacidosis?

A

An abnormally high level of ketone bodies in the blood which reduce pH an causes coma and death

76
Q

When can Ketoacidosis occur?

A
  1. In type I diabetes

2. Pateitns with ultra low carbohydrate diets

77
Q

What happens to the level of ketone boded during fasting?

A

Increases steadily then after 2 days of fasting increases exponentially

78
Q

Describe what happens in ketosis during fasting or uncontrolled type I diabetes

A
  1. Acetyl CoA builds up
  2. Acetyl CoA forms ketone bodies
  3. These ketone bodies are transported through the blood to extra hepatic tissues to be used as fuel
79
Q

How are ketone bodies formed in the liver?

A
  1. A surplus of acetyl CoA forms acetoacetyl CoA
  2. acetoacetyl CoA combines with acetyl CoA to form 3-hydroxy-3methyl-glutaryl CoA
  3. hydroxy-3methyl-glutaryl CoA this then forms acetoacetate which is a ketone body
  4. acetoacetate can spontaneously form acetone
80
Q

What is a characteristic sign of acetone

A

It has a fruity smell

81
Q

How do extra hepatic tissues use ketone bodies?

A
  1. D-3-hydroxy-butyrate reacts with dehydrogenase to form acetoacetate
  2. acetoacetate reacts with succunyl CoA transferase to form acetoacetyl CoA
  3. Acetoacetyl CoA then reacts with thiolase to form 2 acetyl CoA molecules that can enter the citric acid cycle
82
Q

What does succunyl CoA transferase do?

A

Converts acetoacetate into ascetoacetyl CoA

83
Q

What does thiolase do?

A

Converts Acetoacetyl CoA into 2 acetyl CoA molecule

84
Q

What is Diabetic Ketoacidosis

A

When a patient has a very high blood glucose level the avidity of tissued to take up glucose is decreased. Simultaneously the liver is running gluconeogenesis
at high rate and pumping even more glucose into the blood
As diabetics lack insulin the liver thinks the patin is fasting and starts gluconeogenesis and b-oxidation causing flood of ketone bodies to be released into the blood
This surplus of ketone bodies causes the blood pH to drop and the excess glucose causing large osmotic water loss via the kidneys

2nd yr- IBMS- Fatty acids (2 decks)

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