Dirty Biochemistry: Fatty Acid Synthesis

Overview of Fatty Acids

• Types of Fatty Acids:
  • Saturated Fatty Acids: No double bonds between carbon atoms.
  • Unsaturated Fatty Acids: Have at least one double bond between carbon atoms.
  • Monounsaturated Fatty Acids: One double bond.
  • Polyunsaturated Fatty Acids: More than one double bond.
• Essential Fatty Acids:
  • Not synthesized by the body, must be ingested through diet.
  • Decrease risk of cardiovascular disease.
  • Includes omega-3 and omega-6 fatty acids.

Omega Fatty Acids

• Omega-6: Linoleic acid.
• Omega-3s:
  • Alpha-linolenic acid (ALA)
  • Eicosapentaenoic acid (EPA)
  • Docosahexaenoic acid (DHA)
• Ratio Importance: Omega-3 to Omega-6 ratio influences cardiovascular health.
• Conversion Pathway: ALA converts to EPA and DHA.

Fatty Acid Synthesis

• Purpose: Conversion of excess carbohydrates into fatty acids for energy storage.
• Pathway Overview:
  • Glucose -> Pyruvate (via glycolysis) -> Acetyl-CoA (via pyruvate metabolism) -> Citrate (via TCA Cycle) -> Fatty Acids.
  • Citrate Shuttle: Transports citrate out of mitochondria for fatty acid synthesis.

Biochemical Pathway

1. Citrate Exits Mitochondria: Via citrate shuttle.
2. Conversion of Citrate to Acetyl-CoA:
   • Done by ATP citrate lyase.
   • Citrate also splits into oxaloacetate (important for TCA cycle).
3. Acetyl-CoA to Malonyl-CoA:
   • Catalyzed by acetyl-CoA carboxylase.
4. Malonyl-CoA to Palmitate:
   • Catalyzed by fatty acid synthase.

Key Enzymes and Cofactors

• Rate-limiting Enzyme: Acetyl-CoA carboxylase.
• Cofactors:
  • CO2 added in Acetyl-CoA to Malonyl-CoA step.
  • NADPH used in Malonyl-CoA to Palmitate step.

Regulation

• Stimulated by:
  • Insulin: Indicates high glucose availability.
  • Citrate: Drives conversion to fatty acids.
• Inhibited by:
  • Glucagon: Opposes insulin's action.
  • Palmitoyl-CoA (Palmitate): End product feedback inhibition.

Summary Equation

• Net Reaction:
  • 8 Acetyl-CoA + 7 ATP + 14 NADPH -> Palmitate + 7 ADP + 7 Pi + 14 NADP+ + 6 H2O + 8 CoA
• End Product: Palmitate, a 16-carbon fatty acid.

Visual Summary

• Complete Pathway Review:
  • Glucose to Pyruvate -> Acetyl-CoA -> TCA Cycle -> Citrate out of Mitochondria -> Acetyl-CoA -> Malonyl-CoA -> Palmitate.

By mastering these steps and details, you will have a comprehensive understanding of fatty acid synthesis, which is crucial for medical exams like USMLE and COMLEX.