Fat Mobilization

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Fat Mobilization

• Fat mobilization
• Breaks down triacylglycerols in adipose tissue.
• Forms fatty acids and glycerol.
• Hydrolyzes fatty acid initially from C1 or C3 of
  the fat.

Triacylglycerol lipase inhibited by insulin,
stimulated by glucagon and epinephrine.
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Metabolism of Glycerol
glycerol transported to the liver
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Fatty Acid Oxidation Activation
Occurs in the cytoplasm
Requires the input of 2 ATP equivalents
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Fatty Acid Oxidation Transport Across
Mitochondrial Membrane
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Fatty Acid Oxidation
First Oxidation Double Bond Formation
Addition of Water to the Double Bond
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Fatty Acid Oxidation
Second Oxidation Ketone Formation
Cleavage Step
These four reactions (oxidation, hydration,
oxidation, cleavage) repeat removing two carbons
at a time, producing acetylCoA.
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Fatty Acid Oxidation Cycle
first oxidation
H2O
Cycle repeats, removing two carbons each time and
making acetyl-CoA, FADH2, and NADH.
hydration
second oxidation
cleavage
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Fatty Acid Oxidation
Summary of fatty acid oxidation for stearic acid
(C180)
Number of cycles required
8
First oxidation x 8
8 FADH2
16 ATP
Second oxidation x 8
8 NADH
24 ATP
Eight cycles yields 9 acetyl-CoA
1 acetyl-CoA 3 NADH, 1 FADH2, 1GTP
12 ATP
Acetyl-CoA x 9
108 ATP
Initial activation cost
Net energy produced
146 ATP
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Other Roles of AcetylCoA Precursor of Sterols,
Steroids, and Ketone Bodies
First condensation
Second condensation
HMG-CoA reductase (inhibited by
statins)
ketone bodies
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Lipogenesis Fatty Acid Synthesis

• Lipogenesis

Is the synthesis of fatty acids from acetyl CoA.
Occurs in the cytosol.
Uses reduced coenzyme NADPH.
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Fatty Acid Synthesis Lipogenesis
cytoplasm
intermembrane space
matrix
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Fatty Acid Synthesis
Activation of AcetylCoA
(coenzyme biotin)
Acetyl CoA carboxylase is stimulated by insulin
and inhibited by glucagon and epinephrine
Transfer to Acyl Carrier Protein in Fatty Acid
Synthase
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Fatty Acid Synthesis
Condensation Reaction
First Reduction Reaction
Reducing agent is NADPH (corresponding oxidation
reaction in fatty acid oxidation pathway uses
NAD as the oxidizing agent)
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Fatty Acid Synthesis
Dehydration Reaction
Second Reduction Reaction
Reducing agent is NADPH (corresponding oxidation
reaction in fatty acid oxidation pathway uses FAD
as the oxidizing agent)
This cycle repeats using another malonylACP and
adding two more carbons.
Fatty acid released after seven cycles.
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Summary of Lipogenesis
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Fatty Acid Length and Unsaturation

• In fatty acid synthesis
• Shorter fatty acids undergo fewer cycles.
• Longer fatty acids are produced from palmitate
  using special enzymes.
• Unsaturated cis bonds are incorporated into a
  10-carbon fatty acid that is elongated further.

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Regulation of Fatty Acid Synthesis

• In fatty acid synthesis
• A high level of blood glucose and insulin
  stimulates glycolysis and pyruvate oxidation.
• More acetyl CoA is available to form fatty acids.

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Fatty Acid Synthesis
Comparison of oxidation and biosynthesis
Reaction sequence
Electron acceptors and donors
Oxidation NAD, FAD
Biosynthesis NADPH
Cellular location
Oxidation inside mitochondrion
Biosynthesis in cytoplasm
Energy produced or used for C160
7 cycles 7 NADH (21 ATP) 7 FADH (14 ATP) 2
ATP 33 ATP
Transport of 8 acetylCoA to cytoplasm 8 ATP
Synthesis of 7 malonylCoA 7 ATP
7 cycles 14 NADPH (42 ATP)
Total required 57 ATP
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Synthesis of Triacylglycerols
Site liver
Substrates
Glycerol phosphate from dihydroxyacetone
phosphate