Lipid Synthesis & Degradation Flashcards

1
Q

How are fats obtained in the body?

A

Through the diet or de novo from carbohydrates

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2
Q

Give examples of how fats play an essential role in biological functions

A
  • membranes
  • Uptake of lipid soluble
    vitamins
  • Precursors of steroid
    hormones
  • energy store
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3
Q

What is the energy content of 1g of fat compared to proteins or carbohydrates?

A

Over double
1g fat = 37Kj
1g Protein = 17Kj
1g carbohydrate = 16Kj

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4
Q

Where does fat come from in the body?

A

When the calorific intake exceeds consumption, the excess is laid down as fat

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5
Q

What is the most common source of metabollic building blocks?

A

Dietary carbohydrates (some amino acids also used)

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6
Q

Where is the majority of fat synthesised?

A

In the liver

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7
Q

Which part of the body uses fat as their preferred energy source?

A

Tissues e.g. Cardiac muscles

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8
Q

What is palmitic acid?

A

Basic amino acid modified by enzyme to produce fatty acids

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9
Q

Where is fat stored in the body?

A

Adipose tissue

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10
Q

Describe the chemical structure of Fatty acids

A

Contain chains of methyl groups
Terminal carboxyl group
when Double bonds present - in cis formation

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11
Q

Outline how fatty acids are synthesised from glucose

A
  1. Acetyl CoA converted to citrate in mitochondria
  2. Citrate exported to cytosol
  3. Citrate converted back to Acetyl CoA + fatty acid synthesis
  4. Fatty acids used by liver, packaged to get transported
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12
Q

How are essential fatty acids obtained?

A

In the diet

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13
Q

How is Acetyl CoA transported to the cytosol from the mitochondrion?

A

Through citrate malate antiport

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14
Q

What molecules are required for fatty acid synthesis to occur?

A
  • Acetyl CoA
  • NADPH
  • ATP
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15
Q

Where is the NADPH required for fatty acid synthesis formed?

A

40% from Citrate Malate Shuttle

60% from Pentose Phosphate Pathway

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16
Q

Descrive the process of transfer of Acetyl CoA to the cytosol.

A
  1. Pyruvate transported into mitochondria
  2. Pyruvate -> oxaloacetate
  3. oxaloacetate reacts with Acetyl CoA => Citrate
  4. Citrate transported to cytosol
  5. Regenerates oxaloacetate
  6. Oxaloacetate -> malate -> pyruvate
  7. NADPH generated
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17
Q

Summarise fatty acid synthesis

A

The sequential addition of 2 carbon units derived from Acetyl CoA

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18
Q

Where does fatty acid synthesis occur?

A

In the cytosol

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19
Q

How is fatty acid synthesis activated? (positive feedback)

A

Stimulated by Citrate

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20
Q

What inhibits fatty acid synthesis? (negative feedback)

A

Inhibited by Palmatic acid

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21
Q

Write out the equation for the irreversible regulatory step in fatty acid synthesis

A

Acetyl CoA + ATP + HCO3- -> Malonyl CoA + ADP + Pi

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22
Q

What vitamin is requred in order for the regulatory step in fatty acid synthesis to occur?

A

Vitamin Biotin

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23
Q

Describe what occurs during elongation in fatty acid synthesis

A
  • Malonyl residue (from regulatory step) transferred to acyl
    carrier protein (ACP)
  • ACP part of multienzyme complex
  • A second acetyl molecule from Acetyl CoA then transferred
    to ACP
  • acetyl molecule and malonyl residue condense to form the
    Acetoacetyl-ACP complex
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24
Q

What is the Fatty Acid synthase?

A

A multifunctional complex made of all the enzymes required during elongation

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25
Q

How is the enzyme Acetyl CoA Carboxylase inhibited?

A

Phosphorylation inhibits the enzyme

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26
Q

What occurs after the regulatory step has been stimulated?

A

Elongation occurs

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27
Q

What is the significance of ACPs in fatty acid synthesis?

A

Fatty acid syntehsis intermediates are covalently linked to ACPs

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28
Q

When is expression of Acetyl CoA Carboxylase increased?

A

High carbohydrate levels

Low fat levels

29
Q

Which enzyme catalyses the regulatory step in fatty acid synthesis?

A

Acetyl CoA Carboxylase

30
Q

In what structural form does the fatty acid synthase detach?

A

Fatty acid synthase exists as a dimer

31
Q

Where is cholesterol synthesised?

A

Endoplasmic reticulum

32
Q

List important properties of Cholesterol

A
  • Rigid hydrophobic molecule
  • virtually insoluble in water
  • Precursor of sterols, steroids, and bile salts
  • transported in circulation as cholesterol esters
  • can’t be oxidised to O2 or h2o - produces no energy
  • important membrane component
33
Q

Outline the basic stages of cholesterol synthesis

A
  1. Acetate activated by Acetyl CoA
  2. 3-hydroxyl-3-methylglutaryl CoA (HMGCoA) converted to
    mevalonate
34
Q

How many steps involved in the synthesis of cholesterol?

A

Over 30

35
Q

Define the term endogenous

A

Produced/Synthesised within the organism or caused by other

factors within the organism / system

36
Q

Which enzyme involved in its synthesis does cholesterol inhibit?

A

HMGCoA reductase

37
Q

What is the major regulatory step in cholesterol synthesis?

A

Conversion of HMGCoA to mevalonate

38
Q

Why is it difficult to reduce circulating cholesterol levels by diet alone?

A

Endogenous synthesis of cholesterol is increased

39
Q

What 3 steps are required for fatty acid degradation?

A
  • Mobilisation (in adipose)
  • Activation (in liver cytosol)
  • Degradation (in liver mitochondria)
40
Q

Outline the hormone activated mobilisation of fatty acids

A
  1. Glucagon/Adrenaline bind to hormone receptor
  2. Adenyl cyclate activated
  3. many AC molecules activated to convert ATP -> cAMP
  4. cAMP Activates protein kinase
  5. protein kinase phosphorylates triglycerol lipase enzyme
    - causing it to hydrolyse
  6. free fatty acids + glycerol produced
  7. Fatty acids bind to albumin protein and carried out of cell
41
Q

What is the role of fatty acid degradation?

A

Releases energy from reserves stored in adipose tissues

42
Q

Why do the free fatty acids bind to albumin protein?

A

Increases the fatty acid’s solubility (easier to move out of cell)

43
Q

Where are the fatty acids exported to?

A

Target tissues requiring energy

44
Q

Which hormones stimulate fatty acid mobilisation ?

A

Glucagon and adrenaline

45
Q

When is the mobilisation of fatty acids especially significant

A

When food isn’t readily available (starvation / exercise etc.)

46
Q

What is the fate of the glycerol produced in the mobilisation of fatty acids?

A

Absorbed by the liver to undergo gluconeogenesis

47
Q

Which hormone inhibits fatty acid mobilisation?

A

Insulin

48
Q

What happens to fatty acids during degradation in the liver?

A

Transported to the liver and activated by acyl CoA synthase enzyme in cytoplasm

49
Q

How is the Acyl CoA produced, transported from the mitochondria?

A

Binds to alcoholcarnitine and carried across the inner mitochondrial membrane

50
Q

Suggest what the result of a carnitine deficiency would be

A

muscle weakness or even death

51
Q

What inhibits the transport of acyl CoA?

A

Malonyl CoA

52
Q

Describe how activation of fatty acids during degradation occurs

A
  1. Long chain fatty acids react with CoA => acyl CoA produced
    • ATP required from mitichondrial membrane
  2. Acyl CoA transported to inner mitochondrial matrix for
    oxidation using carnitine
53
Q

Summarise what occurs during fatty acid oxidation?

A

Acyl CoA degraded by sequential removal of 2 carbon units

54
Q

What is the fate of fatty acid oxidation products?

A

FADH2 & NADH produce ATP

Acetyl CoA will enter the TCA cycle when glycolysis occurs

55
Q

What product do odd chain lengths yield during fatty acid oxidation?

A

Propanoyl - CoA

56
Q

How much ATP is produced from the process Fatty acid oxidation?

A

Complete oxidation of palmitate yields 106 molecules of ATP

57
Q

What are the products of fatty acid Oxidation?

A

FADH2, NADH and Acetyl CoA produced

58
Q

Define the term ketogenesis

A

Synthesis of ketone bodies

59
Q

Which enzyme removes odd number of double bonds?

A

Isomerase

60
Q

Explain the fate of the following ketone bodies

  • Triglycerides
  • Glycerol
  • Fatty acids
A
  • Triglcerides broken down in adipocytes into FA + glycerol
  • Glycerol fed into glycolysis or gluconeogenesis
  • Fatty Acids activated and transported to mitochondria
  • Fatty Acids broken down into Acetyl CoA
61
Q

How is acetoacetate converted back into Acetyl CoA ?

A

Acetoacetate -> acetoacetyl CoA by CoA transferase

acetoacetyl CoA -> 2- Acetyl CoA by Thiolase

62
Q

What is the process of ketogenesis regulated by?

A

Insulin and Glucagon ratio

63
Q

Why does a low hormone ratio increase ketogenesis?

A

Acetyl CoA carboxylase is inhibited during fatty acid synthesis

64
Q

When does the process of ketogenesis flourish?

A

When Glucagon:insulin ratio is low

65
Q

What is the fate of ketone bodies dependent on?

A

Flow of carbohydrates in glycolysis

66
Q

What is the major use of Ketone bodies?

A

Major enrgy source for cardiac muscles and renal cortex

67
Q

Outline the steps of ketogenesis to produce ketone bodies

A

Acetyl CoA -> Acetoacetyl CoA -> HMGCoA -> Acetoacetate

=> 3-Β-hydroxybuterate / non enzymatically -> acetone

68
Q

Which 2 enzymes remove even numbers of double bonds?

A

Reductase and Isomerase