Fatty Acid Synthesis: 28.1 Stages of FA Synthesis

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CHAPTER 28:

Fatty Acid Synthesis


Problems: 2-4,6-7,10,13-14,21-24
28.1 Stages of FA Synthesis

1. Transfer of acetyl-CoA from


mitochondria to cytosol.
2. Activation of acetyl-CoA;
synthesis of malonyl-CoA.
3. Five step elongation cycle of
FA synthesis via ACP
intermediates.
Transport of Aetyl-CoA from Mitochondria to
Cytoplasm

ATP-citrate lyase
Citrate synthase
Malate
dehydrogenase
Pyruvate
carboxylase Malic enzyme
Sources of NADPH for FA Synthesis
Formation of Malonyl-CoA: Committed Step

Acetyl‐CoA Carboxylase
Fatty Acid Synthesis

• FA are synthesized by the repetitive


condensation of two-carbon units derived from
malonyl CoA
Loading of precursors via thioester derivatives,
followed by chain elongation
(1) Condensation of the precursors
(2) Reduction
(3) Dehydration
(4) Reduction
Loading Stage of FA Synthesis

-SH
Elongation Stage of
FA Synthesis

-ketoacyl synthase
Reduction

-ketoacyl reductase
Condensation

Dehydration

3-hydroxyacyl dehydratase

Reduction

enoyl reductase

The synthesis of palmitic acid requires 7


ATPs and 8 NADPHs: Can you account
for these ATPs and NADPHs?
Fatty Acid Activation

Different synthatases:
Short (<C6)
Medium (C6 – C12)
Long (>C12)
Very long (>C16)
28.2 Elongation and Desaturation
C16:0 to C18:n – C20:n

Elongation occurs with enzymes on the


cytosolic face of the ER membrane.
This is done by elongases that use
malonyl-CoA to add the 2-carbon
subunits.
Oxidase Mammals
C18:0-CoA → C18:19-CoA → C18:29,12-CoA
X
Stearoyl CoA Oleoyl CoA linolenoyl CoA

Dietary source
28.3 Acetyl CoA Carboxylase and
Regulation of FA Metabolism

• High ATP OFF


• Low ATP ON
• High Citrate ON
• High C16:0-CoA OFF
• Malonyl CoA inihbits
carnitine acyl
transferase I. How
does this affect FA
metabolism?
Hormonal Regulation of Acetyl CoA Carboxylase
• Insulin activates
• Glucagon & epinephrine deactivate

Glucagon & epinephrine deactivate via


enhancing acetyl CoA carboxylase inhibition
through the activity of AMP-dependent
kinase.

Insulin stimulates FA synthesis by stimulating


protein phosphatase that activates acetyl
CoA carboxylase.

28.4 Ethanol Metabolism and FA


Synthesis

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