Fatty Acid Synthesis

Introduction

• Fatty Acid Definition: Chemical structure containing a carboxylic acid group and a hydrocarbon chain.
  • Amphiphilic nature: Hydrophilic and hydrophobic properties.
  • Longer hydrocarbon chains are more hydrophobic.

Requirements for Synthesis

• Acetyl-CoA: High levels needed in the cytoplasm.
• NADPH: Derived from the pentose phosphate pathway.
• Location: Occurs in the cytosol (contrast with fatty acid catabolism in mitochondria).

Storage and Usage

• Energy Storage: Fatty acids stored as triglycerides in adipose tissue.
  • Anhydrous, stores more energy per mass compared to glycogen.

Locations in the Body

• Liver and Adipose Tissue: Primary sites for fatty acid synthesis.

Acetyl-CoA Transportation

• Citrate Shuttle: Transports citrate out of mitochondria, converted back to acetyl-CoA in the cytosol by ATP citrate lyase.

Key Enzymes and Reactions

• Acetyl-CoA Carboxylase (ACC): Catalyzes formation of malonyl-CoA from acetyl-CoA.
  • Regulation:
    • Inhibited by glucagon, epinephrine, palmitoyl-CoA, and AMPK.
    • Activated by insulin, citrate, and CHREBP (carbohydrate response element binding protein).
  • Committed and Rate-Limiting Step: Highly regulated.
  • Carboxybiotin: Donates carboxyl group to acetyl-CoA, requires ATP.

Fatty Acid Synthase Complex

• Structure: Large protein complex (250-270 kDa) with acyl carrier protein (ACP) and phosphopantothione.
• Process: Acetyl-CoA and malonyl-CoA bind to complex, leading to chain elongation.

Synthesis Cycle

• Initial Binding: Acetyl-CoA binds to ACP, malonyl-CoA binds and undergoes condensation with acetyl-CoA.
  • Butyryl-CoA (4 carbons) formed.
  • Malonyl-CoA acts as a two-carbon donor, releases CO2.

Chain Elongation

• Repeated Cycles:
  • Malonyl-CoA donates two carbons, undergoes:
    • Condensation
    • Reduction (using NADPH)
    • Dehydration
    • Reduction
  • Continues until palmitate (16-carbon chain) is formed.

Final Product and Cycle Summary

• End Product: Palmitate (16-carbon, saturated fatty acid).
• Cycle Details:
  • Total of 7 cycles: Uses 7 malonyl-CoA, 2 NADPH per cycle.
  • Total 14 NADPH and 7 ATP used.
  • 7 CO2 produced.

Overall Reaction Equation

• Inputs: 8 acetyl-CoA, 14 NADPH, 7 ATP, 14 H⁺.
• Outputs: Palmitic acid and recycled reaction components.

Conclusion

• Emphasizes the importance of fatty acid synthesis in energy storage and its complex regulation and process.