Fat as Fuel Flashcards
What are the biological functions of lipids?
- Components of cell membranes
(phospholipids & cholesterol) - Precursors of hormones cholesterol steroid hormones arachidonic acid prostaglandins
- Long term fuels
(triglycerides)
What is the efficiency of triglycerides as fuel?
- 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
Structure of triglyceride fat (triacylglycerols)?
common fatty acids
palmitic acid - 160
stearic acid 18:0
oleic acid 18:1
linoleic acid 18:2
linolenic acid 18:3
How does the breakdown of stored triglyceride fat occur?
- 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
What enzymes are used to break triglycerol down?
and how is it activated?
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
What happens to the free fatty acid after breakdown of triglycerol?
Free fatty acids travel in plasma bound to albumin
* Act as fuels for muscles,heart & liver
What happens to glycerol after breakdown of triglycerol?
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
How does fatty acid matabolism occur?
- 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
How are fatty acids activated?
Long chain fatty acids are activated in the cytosol by the addition of CoA.
What are bonds formed in activation of fatty acid?
Coenzyme A forms thioester bonds with carboxylic acids
Describe Transport of fatty acyl-CoA into mitochondria using the carnitine shuttle?
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.
How would you describe the energy of the process?
The process is energetically neutral.
Describe stage 1 of the transport of fatty acids into mitochondria?
Describe stage 2 of the transport of fatty acids into mitochondria?
Why is it called B-oxidation?
Called β-oxidation because the β-carbon undergoes oxidation to produce a carbonyl group (carbon double-bonded to oxygen).
Describe B-oxidation?
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.
What is an overview of β-oxidation pathway?
- Remove 2 hydrogens
- Add oxygen (in water)
- Remove 2 hydrogens
- Cleave bond and add CoASH
Describe the first reaction in beta oxidation?
Reaction 1 - Removal of 2 H atoms
Describe the second reaction in beta oxidation?
Reaction 2 – Addition of water
Describe the third reaction in beta oxidation?
Reaction 3 – Removal of 2 H atoms
Describe the forth reaction in beta oxidation?
Reaction 4 - Removal of 2 C units
What happens to the fatty acyl-CoA
Shorter fatty acid re enters reactions 1 - 4
Fatty acyl-CoA (2 C atoms shorter)
Summary of B-oxidation pathway 1
Summary of B-oxidation pathway -2
How many molecules produced?
Fatty acid with 16 C atoms will pass through 7 repeats of -oxidation pathway producing 7 NADH & 7 FADH2
What will fatty acids with 16C C atoms produce?
Fatty acid with 16 C atoms will give rise to 8 acetyl CoA which CoA enter the TCA cycle
What is the energy yield from fatty acid oxidation?
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
Regulation of fat metabolism
- 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
How does the metabolism of odd numbered fatty acids?
B-oxidation will result in the following:
C15—>C13—>C11—>C9—>C7—->C5—->C3
How to deal with the last 3 carbons in metabolism of odd numbered fatty acids?
Describe Ketone body formation?
- ‘Ketogenesis’ occurs when fat metabolism is the main source of energy:
– in starvation
– in Type I diabetes
What does fatty acid oxidation in hepocytes lead to?
- 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
How can Ketone bodies can be utilised for energy by most tissues?
- 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
Why can’t some tissues utilise FA energy?
- 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?
Summary of mitochondrial events
