Fat Metabolism and Fatty Acid Synthesis

Introduction

• Ultimate Goal: Deliver triglycerides (TG) or free fatty acids (FFA) into the bloodstream to reach capillary beds.
  • TG: Chemical name for a fat molecule.
  • FFA: Monomer subunits of fat molecules.
• Importance: These molecules diffuse to surrounding tissues (e.g., muscle or heart tissue) for ATP production.

Sources of Triglycerides and Free Fatty Acids

1. Diet
   • Small intestine digests food and packages fat molecules into chylomicrons.
2. Liver Synthesis
   • Excess glucose is converted to fatty acids.
   • Fatty acids are packaged into triglycerides, along with cholesterol, into very low-density lipoprotein (VLDL).
   • VLDL enters the bloodstream and is taken up by tissues, possibly stored by adipose cells.
   • Process: Glucose → Fatty Acids.

Fatty Acid Synthesis

• Focus: Converting glucose into fatty acids inside liver cells.
• Cellular Level Overview:
  • Key Compartments: Cytoplasm and mitochondria (with inner and outer membranes).
  • Electron Transport Chain: Located on the inner mitochondrial membrane.
  • Krebs Cycle: Breaks down glucose after glycolysis in the cytoplasm.

Glucose Breakdown Process (Quick Review)

1. Glycolysis
   • Glucose (6-carbons) → 2 Pyruvate (3-carbons each).
   • Occurs in the cytoplasm.
2. Pyruvate Transport
   • Pyruvate transported to the mitochondrial matrix.
3. Pyruvate Dehydrogenase
   • Converts Pyruvate → Acetyl-CoA (2-carbon molecule).
   • Acetyl-CoA enters the Krebs cycle.
4. Krebs Cycle
   • Acetyl-CoA (2 carbons) + Oxaloacetate (4 carbons) → Citrate (6 carbons).
   • Citrate is modified and releases 2 carbons as CO₂.
   • Produces NADH and FADH₂ which help in ATP production.

Converting Glucose to Fatty Acids

• Challenge: Acetyl-CoA is in mitochondria; fatty acid synthesis enzymes are in the cytoplasm.
• Solution: Citrate Shuttle
  • Citrate can cross the mitochondrial membrane.
  • Cytoplasmic enzymes break citrate into oxaloacetate and acetyl-CoA.
• Recycling of Oxaloacetate
  • Oxaloacetate converts to pyruvate, which returns to mitochondria to restart the cycle.
  • Conversion produces NADPH, aiding in fatty acid synthesis.

Significance of NADPH

• Source of Reducing Power: Crucial for anabolic reactions (e.g., forming carbon-carbon bonds in fatty acids).
• Additional Production: Pentose Phosphate Pathway and the citrate shuttle process.

Summary

• Acetyl-CoA is now in the cytoplasm, ready for fatty acid synthesis.
• Requirements:
  • ATP for energy.
  • NADPH for reducing power.
• Next Steps: Detailed look at converting acetyl-CoA to fatty acids.