Fatty acid Synthesis Flashcards

1
Q

Is fatty acid synthesis the reverse of beta oxidation?

A

No

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2
Q

Where does fatty acid synthesis take place?

A

Takes place in our liver cells and in lactating mammary glands

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3
Q

In which part of the cell does fatty acid synthesis occur?

A

In the cytosol

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4
Q

How is citrate shuttled out of the inner mitochondrial membrane?

A

Via the pyruvate malate cycle

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5
Q

Why is the pyruvate malate cycle important?

A
  1. It shuttles out our citrate

2. Helps generate NADPH for the pentose phosphate cycle

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6
Q

Name the 3 carbon intermediate that is important or fast acid synthesis to occur

A

Malonyl CoA

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7
Q

How is malonyl CoA formation require?

A

Acetyl CoA in an irreversible reaction

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8
Q

Name the rate determining step for fatty acid synthesis

A

The formation of malonyl CoA

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9
Q

How is malonyl CoA formed?

A

Acetyl CoA reacts with Acetyl CoA carboxylase (biotin) and citrate to form malonyl CoA

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10
Q

State the 2 equators involved in the production of malonyl CoA

A
  1. Biotin-enzyme + ATP + HCO3 -> CO2-Biotin-enzyme + ADP+ Pi

2. CO2-Biotin-enzyme + acetyle CoA -> malonyl CoA + Biotin-enzyme

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11
Q

Name a step which inhibits or activates fatty acid synthesis

A

The formation of malonyl CoA

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12
Q

How is the formation of malonyl CoA regulated?

A

By regulating the enzyme acetyl CoA carboxylase

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13
Q

When do we want a lot of malonyl CoA to be produced?

A

When we have a low AMP:ATP ratio (ie when we don’t have a lot of energy)

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14
Q

How is Acetyl CoA

carboxylase inactivated?

A

When there’s a high AMP:ATP ratio up regulates kinase phosphorylating our Acetyl CoA
carboxylase inactivating it

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15
Q

How is Acetyl CoA

carboxylase activated?

A

Increased insulin and decreased glucagon up regulates Phosphatase which removes a phosphate group from Acetyl CoA
carboxylase activating it

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16
Q

What does the fatty enzyme synthase complex do?

A

It catalyses different enzymatic activities to synthesis and elongate fatty acids

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17
Q

Describe the central part of the fatty acid synthesis complex

A

It is a domain where the molecule 4’ phosphopentetheine covalently bonds to the enzyme

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18
Q

What is 4’ phosphopentetheine ?

A

It is a derivative of the vitamin pantothenic acid and it is also a component of CoA

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19
Q

What does 4’ phosphopentetheine do?

A

It carries acetyl and act units on the terminal thiol group during fatty acid synthesis

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20
Q

Name all the steps of fatty acid synthesis

A
  1. Transfer from acetyl CoA to the SH group of the Acyl Carrier Protein
  2. Transfer of a 2 carbon fragment on our ACP onto a cystine residue on the enzyme
  3. Addition of the malonate unit from malonyl CoA onto a vacant ACP
  4. Acetyl attack the malonyl group
  5. Reduction of acetoacetyl-S-ACP
  6. Dehydration of beta-hydroxybutyryl-ACP to introduce a double bond
  7. Reduction of crotonyl-S-ACP
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21
Q

How is acetyl CoA transferred onto the acyl carrier protein (ACP)?

A

Via the enzyme Acetyl CoA-ACP transacylase

this forms Acetyl-S-CAP + CoA

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22
Q

What does Acetyl CoA-ACP transacylase do?

A

It transfers acetyl CoA transferred onto the acyl carrier protein (ACP)

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23
Q

What happens to Acetyl-S-CAP once it has formed?

A

It combines with an enzyme-sulpha hydrate too form Acetyl-S-Enzyme + ACP-SH
(no enzyme required)

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24
Q

What is malonate added to and how

A

Malonyl CoA is reacted with ACP-SH via the enzyme Malonyl CoA-ACP-transacylase
to form Malonyl-S-ACP + CoA

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25
Q

What does Malonyl CoA-ACP-transacylase do?

A

Reacts Malonyl CoA and ACP-SH together to form malonyl-S-ACP +CoA

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26
Q

What happens to Malonyl-S-ACP once it has formed?

A

It is attacked by acetyl groups

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27
Q

What happens to malonyl S ACP once it is attacked by acetyl groups?

A

It loses a CO2

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28
Q

Why is malonyl-S-ACP losing CO2 an important step?

A

It is a key step in providing the reaction with energy as the decarboxylation drives the reaction

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29
Q

How does the malonyl-S-ACP lose a CO2?

A

It undergoes an acetyl attack and is reacted with the enzyme B-Ketoacyl-ACP synthase to form acetoacetyl-S-ACP

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30
Q

What does B-Ketoacyl-ACP synthase do?

A

It aids in the conversions of malonyl-S-ACP into acetoacetyl-S-ACP

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31
Q

What happens to acetoacetyl-S-ACP once it has formed?

A

It Is reduced by NADPH to for beta-hydroxybutyryl-ACP by the enzyme b-Ketoacyl-ACP reductase

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32
Q

What does the enzyme b-Ketoacyl-ACP reductase do?

A

It aids in the reduction of acetoacetyl-S-ACP into beta-hydroxybutyryl-ACP

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33
Q

What happens to beta-hydroxybutyryl-ACP once it as formed?

A

It is dehydrated by b-hydroxyacyl-ACP

dehydratase to form crotonyl-S-ACP

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34
Q

What does b-hydroxyacyl-ACP

dehydratase do?

A

It dehydrates beta-hydroxybutyryl-ACP to form crotonyl-S-ACP

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35
Q

What happens to crotonyl-S-ACP once it has formed?

A

It is reduced by NADP and Enoyl-ACP reductase do form butyryl-S-ACP + NADP+

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36
Q

What doesEnoyl-ACP reductase do?

A

It reduces crotonyl-S-ACP to form butyryl-S-ACP

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37
Q

At the end of the 7 steps of fatty acid synthesis what is produced?

A

A 4 carbon compound is produced which has 3 terminal carbons fully saturated

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38
Q

After the 7 steps of fatty acid synthesis what happens?

A

These 7 steps are repeated in the sequence 5 times beginning with the transfer of the newly formed 4 carbon species from the ACP to the peripheral cysteine side group

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39
Q

After the sequence of fatty acid produce has been repeated 6 times what is the end result?

A

The cycle is repeated until a fully saturate 16 carbon long fatty acid chain forms

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40
Q

What happens when a fatty acid with 16 carbons is synthesised?

A

The synthetic process is terminated as a fully saturated molecule of palmitate is formed

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41
Q

State the overall reaction for palmitate synthesis

A

8Acetyl CoA + 14NADPH + 14H+ +7ATP
->
Palmitate + 14NADP+ +8CoA +7ADP +H2O

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42
Q

Name the principal product of fatty acid synthesis?

A

palmitate

43
Q

What happens to palmitate once it has formed?

A

It can be lengthened to form stearate

44
Q

How long is stearate?

A

It can be 18 carbons in length or longer

45
Q

How are fatty acids longer than 18 carbons made?

A

They are made by further sequential additions of acetyl groups (This requires a different set of enzymes)

46
Q

Where are the enzymes that produce larger fatty acids found?

A

They are found on the endoplasmic reticulum and in the mitochondria

47
Q

Describe the enzyme pathway in the endoplasmic reticulum

A

All enzymes are discreet and are sutuated on the surface of the smooth endoplasmic reticulum
There is no acyl carrier protein all intermediates are bound to CoA

48
Q

What is the mitochondrial pathway of fatty aid synthesis important for?

A

Important for the lengthening of short fatty acid chains

49
Q

What is not needed in the mitochondrial pathway ?

A

The intermediate malonyl CoA is not needed

Intermediates are directly added to acetyl CoA

50
Q

What occurs at the smooth endoplasmic reticulum

A

The addition of double bonds to unsaturated fatty acids

51
Q

What is the desaturation of fatty acids?

A

It is the addition of a double bond to unsaturated fatty acids
It is a series of electron carriers consisting of 3 enzymes

52
Q

Name the 3 enzymes involved in the desaturation of fatty acids

A
  1. NADH-Cytochrome b5 reductase
  2. cytochrome b5
  3. Fatty acid desaturase
53
Q

What does NADH-Cytochrome b5 reductase do?

A

It reduces FAD into FADH2

54
Q

What does cytochrome b5 do?

A

It reduces Fe3+ INTO Fe2+

55
Q

What does fatty acid desaturase do?

A

It reduces Fe3+ INTO Fe2+

56
Q

What do NADH Cytochrome b5 reductase, cytochrome b5 and Fatty acid desaturase do?

A

Over all they pass 2 pairs of electrons down a series of redox reactions to ultimately produce a double bond at the carbon 2,5,6 or 9 position in fatty acids

57
Q

How many different desaturase enzymes do we have and what do they do?

A

Mammilian systems have 4 different desaturase enzymes that produce double bonds at the carbon 2,5,6 or 9 positions

58
Q

How can fatty acids be different?

A

They can vary in their degree of saturation

59
Q

How can we define the configuration of double bonds in fatty acids?

A

Can be defined as cis and trans

60
Q

IF you describe a fatty acid as cis what does that mean?

A

Means the ethyl groups are on the same side of the double bonds

61
Q

IF you describe a fatty acid as trans what does that mean?

A

Means the methyl groups are on the opposite side of the double bonds

62
Q

How do we indicate where the double bond is?

A

By using a triangle followed by a number

63
Q

Why are unsaturated fatty acids important?

A

As they are an important precursor to intracellular messages
and phospholipids

64
Q

On which carbons can mammals form double bonds on in fatty acid chains?

A

Carbons: 4,5,6, and 9

65
Q

Where do we get particular polyunsaturated fatty acids that we can’t synthesise?

A

We get them from our diet

66
Q

Name some essential fatty acids

A
  1. Alpha-linolenic acid
  2. Linoleic acid
  3. Gamma linoleum acid
  4. Arachidonic acid
67
Q
State:
a. how Many carbons 
b. How many double bonds 
c. Position of double bonds
in Alpha-linolenic acid
A

a. 18 carbons
b. 3 double bonds
c. cis carbons on: 9,12,15

68
Q
State:
a. how Many carbons 
b. How many double bonds 
c. Position of double bonds
in linolenic acid
A

a. 18 carbons
b. 2 double bonds
c. cis carbons on 9,12

69
Q
State:
a. how Many carbons 
b. How many double bonds 
c. Position of double bonds
in gamma-linolenic acid
A

a. 18 carbons
b. 3 double bonds
c. cis carbons on: 6,9,12

70
Q
State:
a. how Many carbons 
b. How many double bonds 
c. Position of double bonds
in Arachidonic acid
A

a. 20 carbons
b. 4 double bonds
c. cis carbons on: 5,8,11,14

71
Q

What can Arachidonic acid be synthesised from

A

Can be synthesis from linoleic acid through a series of desaturation and elongation reaction

72
Q

If you can’t synthesis Arachidonic acid from linoleic acid where do you need to get Arachidonic acid from?

A

Need to get it from meat as it is not present in plants

73
Q

Why is Arachidonic acid important?

A

It is an important precursor of several classes of signalling molecules

74
Q

How can arachidonate be released?

A

In response to hormonal or other stimuli phospholipase A2 attacks membrane phospholipids releasing arachidonate

75
Q

What do derivatives of arachidonate do?

A

They are potent biological signalling molecules that at as short range messengers which affect the tissues near the cells that produce them

76
Q

What can arachidonate be converted to and where?

A

Enzymes of the smooth ER can convert arachidonate into prostaglandins forming an intermediate precursor Prostaglandin H2

77
Q

What can inhibit Prostaglandin synthase and how?

A

Aspirin by blocking channel to the active site

78
Q

What does aspirin do to cox?

A

It irreversibly inactivates the cyclooxygenase activity of COX by acetylene a serine and blocking the active site
This prevents the formation of prostaglandins and thromboxanes

79
Q

How many COX enzymes are there?

A

2

80
Q

What does cyclooxygenase-2 (COX-2) do?

A

It is an enzyme that syntheses prostaglandins

81
Q

What are prostaglandins?

A

They are molecules that promote inflammation, pain and fever

82
Q

What are NSAIDs?

A

Non steroidal anti-inflammatory drugs

83
Q

How do NSAIDs work?

A

They work by blocking cyclooxyrgenase-2 (COS-2) thus preventing the synthesis of prostaglandins

84
Q

What are the disadvantages of NSAIDs?

A

They also inhibit COX-1 this can lead to side effects such as ulcerations and kidney damage

85
Q

How are fatty acids stored?

A

As components of triacylglycerols

86
Q

What are monoacylglycerols

A

1 molecule of fatty acid esterified to a molecule of glycerol

87
Q

What are diacylglycerols

A

2 molecules of fatty acids esterified to a molecule of glycerol

88
Q

What are triacylglycerols

A

3 molecules of fatty acids esterified to a molecule of glycerol

89
Q

How are fatty acids esterifed to glycerols?

A

They are esterfied by their carboxyl groups leading to the formation of neutral fats

90
Q

Can triacylglycerols form micelles?

A

Not on their own they need to coalesce within adipocytes to

Form oily droplets that are anhydrous

91
Q

Why are triacylglycerols important?

A

As they are a major energy source

92
Q

In a triacylglycerols are all the fatty acids attached to glycerol the same?

A

No they can be different

93
Q

What mist happen to fatty acids before they can turn into triacylglycerols ?

A

They must first be activated

94
Q

Name the initial acceptor of fatty acids during the synthesis of TAGs?

A

Glycerol-3- phosphate

95
Q

How can glycerol-3 phosphate be produced?

A
  1. By the liver

2. By adipose tissue

96
Q

How is glycerol-3-phosphate produced by the liver?

A

Glycerol reacts with glycerol kinase to form glycerol-3- phosphate
This reaction requires ATP

97
Q

What does glycerol kinase do?

A

It aids in the conversion of glycerol of glycerol-3-phophate

98
Q

How is glycerol-3- phosphate produced by adipose tissue?

A
  1. Glucose is converted into dihydropxyacetone (DHAP)

2. DHAP is then reduced by NADH and glycerol 3 dehydrogenase to form glycerol 3 phosphate

99
Q

What does glycerol-3- dehydrogenase do?

A

It aids in the conversion of DHAP into glycerol 3 phosphate

100
Q

How are TAGs synthesised by glycerol 3 phosphate?

A
  1. Glycerol 3 phosphate reacts with fatty acyl-COA and acyltransferase to form Phosphatidate, 2 CoAs
  2. Phosphatidate then reacts with phosphatase to form diacylglycerol
  3. diacylglycerol recat. with fatty acyl-COA and acyltransferase to form the glycerol backbone
101
Q

What does acyltransferase do when it is rented with glycerol-3-phophate ?

A

It aids in the conversion of glycerol-3-phophate into Phosphatidate

102
Q

What does phosphatase do?

A

Aids in the reaction of Phosphatidate into diacylglycerol

103
Q

What does acyltransferase do when it is rented with diacylglycerol

A

Aids in the reaction of diacylglycerol into a glycerol backbone