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
How is the enzyme Acetyl CoA Carboxylase inhibited?
Phosphorylation inhibits the enzyme
26
What occurs after the regulatory step has been stimulated?
Elongation occurs
27
What is the significance of ACPs in fatty acid synthesis?
Fatty acid syntehsis intermediates are covalently linked to ACPs
28
When is expression of Acetyl CoA Carboxylase increased?
High carbohydrate levels | Low fat levels
29
Which enzyme catalyses the regulatory step in fatty acid synthesis?
Acetyl CoA Carboxylase
30
In what structural form does the fatty acid synthase detach?
Fatty acid synthase exists as a dimer
31
Where is cholesterol synthesised?
Endoplasmic reticulum
32
List important properties of Cholesterol
- 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
Outline the basic stages of cholesterol synthesis
1. Acetate activated by Acetyl CoA 2. 3-hydroxyl-3-methylglutaryl CoA (HMGCoA) converted to mevalonate
34
How many steps involved in the synthesis of cholesterol?
Over 30
35
Define the term endogenous
Produced/Synthesised within the organism or caused by other | factors within the organism / system
36
Which enzyme involved in its synthesis does cholesterol inhibit?
HMGCoA reductase
37
What is the major regulatory step in cholesterol synthesis?
Conversion of HMGCoA to mevalonate
38
Why is it difficult to reduce circulating cholesterol levels by diet alone?
Endogenous synthesis of cholesterol is increased
39
What 3 steps are required for fatty acid degradation?
- Mobilisation (in adipose) - Activation (in liver cytosol) - Degradation (in liver mitochondria)
40
Outline the hormone activated mobilisation of fatty acids
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
What is the role of fatty acid degradation?
Releases energy from reserves stored in adipose tissues
42
Why do the free fatty acids bind to albumin protein?
Increases the fatty acid's solubility (easier to move out of cell)
43
Where are the fatty acids exported to?
Target tissues requiring energy
44
Which hormones stimulate fatty acid mobilisation ?
Glucagon and adrenaline
45
When is the mobilisation of fatty acids especially significant
When food isn't readily available (starvation / exercise etc.)
46
What is the fate of the glycerol produced in the mobilisation of fatty acids?
Absorbed by the liver to undergo gluconeogenesis
47
Which hormone inhibits fatty acid mobilisation?
Insulin
48
What happens to fatty acids during degradation in the liver?
Transported to the liver and activated by acyl CoA synthase enzyme in cytoplasm
49
How is the Acyl CoA produced, transported from the mitochondria?
Binds to alcoholcarnitine and carried across the inner mitochondrial membrane
50
Suggest what the result of a carnitine deficiency would be
muscle weakness or even death
51
What inhibits the transport of acyl CoA?
Malonyl CoA
52
Describe how activation of fatty acids during degradation occurs
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
Summarise what occurs during fatty acid oxidation?
Acyl CoA degraded by sequential removal of 2 carbon units
54
What is the fate of fatty acid oxidation products?
FADH2 & NADH produce ATP | Acetyl CoA will enter the TCA cycle when glycolysis occurs
55
What product do odd chain lengths yield during fatty acid oxidation?
Propanoyl - CoA
56
How much ATP is produced from the process Fatty acid oxidation?
Complete oxidation of palmitate yields 106 molecules of ATP
57
What are the products of fatty acid Oxidation?
FADH2, NADH and Acetyl CoA produced
58
Define the term ketogenesis
Synthesis of ketone bodies
59
Which enzyme removes odd number of double bonds?
Isomerase
60
Explain the fate of the following ketone bodies - Triglycerides - Glycerol - Fatty acids
- 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
How is acetoacetate converted back into Acetyl CoA ?
Acetoacetate -> acetoacetyl CoA by CoA transferase | acetoacetyl CoA -> 2- Acetyl CoA by Thiolase
62
What is the process of ketogenesis regulated by?
Insulin and Glucagon ratio
63
Why does a low hormone ratio increase ketogenesis?
Acetyl CoA carboxylase is inhibited during fatty acid synthesis
64
When does the process of ketogenesis flourish?
When Glucagon:insulin ratio is low
65
What is the fate of ketone bodies dependent on?
Flow of carbohydrates in glycolysis
66
What is the major use of Ketone bodies?
Major enrgy source for cardiac muscles and renal cortex
67
Outline the steps of ketogenesis to produce ketone bodies
Acetyl CoA -> Acetoacetyl CoA -> HMGCoA -> Acetoacetate | => 3-Β-hydroxybuterate / non enzymatically -> acetone
68
Which 2 enzymes remove even numbers of double bonds?
Reductase and Isomerase