Fat as Fuel Flashcards

1
Q

What are the biological functions of lipids?

A
  1. Components of cell membranes
    (phospholipids & cholesterol)
  2. Precursors of hormones cholesterol steroid hormones arachidonic acid prostaglandins
  3. Long term fuels
    (triglycerides)
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2
Q

What is the efficiency of triglycerides as fuel?

A
  • Compact storage - triglycerides stored as large fat droplets in the fat cells of adipose tissue
  • Large body stores -
    70 kg adult has: 11 kg fat (as TG)
    120 g glycogen in liver
    10 g glucose
    *Efficiency on weight basis
    1 g fat yields 38 kJ
    1 g protein 21 kJ
    1 g carbohydrate 17 kJ
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3
Q

Structure of triglyceride fat (triacylglycerols)?

common fatty acids

A

palmitic acid - 160
stearic acid 18:0
oleic acid 18:1
linoleic acid 18:2
linolenic acid 18:3

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4
Q

How does the breakdown of stored triglyceride fat occur?

A
  • in adipose tissue
  • Triacylglcerol broken down into diaclycerol and a fatty acid then to monoacylglycerol and a fatty acid then glycerol and a fatty acid
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5
Q

What enzymes are used to break triglycerol down?
and how is it activated?

A

Lipase activated by adrenaline and glucagon
* Broken down from triglycerol by triacylglcerol lipase (active)
* broken down from diacylglcerol by DAG lipase
* Broken down to glycerol MAG Lipase

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6
Q

What happens to the free fatty acid after breakdown of triglycerol?

A

Free fatty acids travel in plasma bound to albumin
* Act as fuels for muscles,heart & liver

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7
Q

What happens to glycerol after breakdown of triglycerol?

A

Metabolism of glycerol
* its water soluble due to 30OH Group and taken up by all tissues

In Most Tissues: Enters glycolysis pathway for conversion to pyruvate, then into TCA cycle for oxidation to CO2
In Liver/In Starvation: Enters glycolysis pathway and is converted to glucose by gluconeogenesis

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8
Q

How does fatty acid matabolism occur?

A
  • By B-oxidation pathway
  • Occurs in mitochondrial matrix(transport across membrane)
  • intermediates present as CoA thioesters (High Energy bonds)
  • biological energy of fatty acid molecule is conserved as the transfer of 2 H atoms to the cofactors NAD + and FAD to form NADH & FADH 2 (no direct ATP synthesis)
  • Series of four enzyme reactions results in removal of two carbon unit as acetyl CoA
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9
Q

How are fatty acids activated?

A

Long chain fatty acids are activated in the cytosol by the addition of CoA.

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10
Q

What are bonds formed in activation of fatty acid?

A

Coenzyme A forms thioester bonds with carboxylic acids

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11
Q

Describe Transport of fatty acyl-CoA into mitochondria using the carnitine shuttle?

A

1) Fatty acyl-CoA freely diffuses across the outer mitochondrial membrane
2) Fatty acid group transferred to carnitine by carnitine acyltransferase I, creating fatty acyl-carnitine.
3)** Fatty acyl-carnitine crosses the inner mitochondrial membrane** via a translocase
4) Carnitine is switched back for CoA by carnitine acyltransferase II, recreating fatty acyl-CoA.
5) Carnitine transported back into the intermembrane space.

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12
Q

How would you describe the energy of the process?

A

The process is energetically neutral.

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13
Q

Describe stage 1 of the transport of fatty acids into mitochondria?

A
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14
Q

Describe stage 2 of the transport of fatty acids into mitochondria?

A
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15
Q

Why is it called B-oxidation?

A

Called β-oxidation because the β-carbon undergoes oxidation to produce a carbonyl group (carbon double-bonded to oxygen).

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16
Q

Describe B-oxidation?

A

One round of β-oxidation produces acetyl-CoA and a fatty acyl-CoA that is 2 carbons shorter - the 2 carbons are now carried by acetyl-CoA.

17
Q

What is an overview of β-oxidation pathway?

A
  1. Remove 2 hydrogens
  2. Add oxygen (in water)
  3. Remove 2 hydrogens
  4. Cleave bond and add CoASH
18
Q

Describe the first reaction in beta oxidation?

A

Reaction 1 - Removal of 2 H atoms

19
Q

Describe the second reaction in beta oxidation?

A

Reaction 2 – Addition of water

20
Q

Describe the third reaction in beta oxidation?

A

Reaction 3 – Removal of 2 H atoms

21
Q

Describe the forth reaction in beta oxidation?

A

Reaction 4 - Removal of 2 C units

22
Q

What happens to the fatty acyl-CoA

A

Shorter fatty acid re enters reactions 1 - 4
Fatty acyl-CoA (2 C atoms shorter)

23
Q

Summary of B-oxidation pathway 1

A
24
Q

Summary of B-oxidation pathway -2
How many molecules produced?

A

Fatty acid with 16 C atoms will pass through 7 repeats of -oxidation pathway producing 7 NADH & 7 FADH2

25
Q

What will fatty acids with 16C C atoms produce?

A

Fatty acid with 16 C atoms will give rise to 8 acetyl CoA which CoA enter the TCA cycle

26
Q

What is the energy yield from fatty acid oxidation?

A

Fatty acid with 16 C atoms goes through 7 repeats of B-oxidation producing 7 NADH & 7 FADH2

ATP yield = 7 x 2.5 + 7 x 1.5 = 28

Fatty acid with 16 C atoms produces 8 acetyl CoA
ATP yield from complete oxidation of acetyl CoA by TCA cycle = 8 x10 ATP = 80

TOTAL = 80+28=108–1 =107
-1 is accounting for ATP used for activation

27
Q

Regulation of fat metabolism

A
  • Release of fatty acids from adipose tissue adrenaline & glucagon activate lipase enzyme
  • Rate of entry into mitochondria via carnitine shuttle
  • Rate of reoxidation of cofactors NADH & FADH2 by Electron Transport Chain
28
Q

How does the metabolism of odd numbered fatty acids?

A

B-oxidation will result in the following:
C15—>C13—>C11—>C9—>C7—->C5—->C3

29
Q

How to deal with the last 3 carbons in metabolism of odd numbered fatty acids?

A
30
Q

Describe Ketone body formation?

A
  • ‘Ketogenesis’ occurs when fat metabolism is the main source of energy:
    – in starvation
    – in Type I diabetes
31
Q

What does fatty acid oxidation in hepocytes lead to?

A
  • Fatty acid oxidation in hepatocytes leads to high concentrations of Acetyl Co A - exceeds capacity of the TCA cycle.
  • Excess Acetyl CoA is converted into ‘ketone bodies’ in liver
  • acetoacetate and β hydroxybutyrate are released into the bloodstream
32
Q

How can Ketone bodies can be utilised for energy by most tissues?

A
  • acetoacetate and β hydroxybutyrate are released into the bloodstream.
  • In most cell types they can be converted back into TCA cycle intermediates (acetyl CoA and succinate).
  • Most tissues oxidise a mixture of fatty acids and ketone bodies
33
Q

Why can’t some tissues utilise FA energy?

A
  • Liver cannot utilise ketone bodies – WHY?
  • Brain cannot utilise fatty acids – WHY?
    – uses glucose and small amount of ketone bodies (‘emergency fuel’)
  • Red blood cells cannot utilise fatty acids or ketone bodies, use glucose only – WHY?
34
Q

Summary of mitochondrial events

A