Fatty Acid Oxidation

Jun 16, 2024

Fatty Acid Oxidation

Introduction

  • Key process after fat mobilization
  • Involves breakdown of triglycerides into glycerol and fatty acids
  • Transport fatty acids to various tissues (heart muscle, skeletal muscle, liver)

Tissues Utilizing Fatty Acids

  • Heart Muscle: Major consumer of fatty acids
  • Skeletal Muscle: Utilizes fatty acids for energy
  • Liver: Important for generating ketone bodies

Mechanism of Fatty Acid Oxidation

Step 1: Activation

  • Free fatty acids need to be converted to prevent them from escaping the cell.
  • Enzyme: Fatty acyl-CoA synthetase
    • Converts fatty acids into fatty acyl-CoA by utilizing ATP (makes ADP + Pi)
    • Structure: Free fatty acid + CoA = Fatty acyl-CoA

Step 2: Transport into Mitochondria

  • Fatty acyl-CoA cannot directly enter mitochondria due to CoA group
  • Carnitine acts as a transporter
    • Carnitine acyltransferase I (Outer Membrane)
      • Converts fatty acyl-CoA into fatty acyl-carnitine (removes CoA)
    • Fatty acyl-carnitine transported via translocase
    • Carnitine acyltransferase II (Inner Membrane)
      • Converts fatty acyl-carnitine back to fatty acyl-CoA (adds CoA back)
      • Carnitine recycled back into cytosol

Step 3: Beta-Oxidation Cycle

  • Process to break down fatty acyl-CoA within the mitochondrial matrix

Nomenclature

  • Number 1 Carbon: Alpha carbon
  • Number 2 Carbon: Beta carbon

First Step: Dehydrogenation

  • Enzyme: Acyl-CoA dehydrogenase
    • Converts FAD to FADH2
    • Forms a double bond between alpha and beta carbons

Second Step: Hydration

  • Enzyme: Enoyl-CoA hydratase
    • Adds water across the double bond
    • Converts into trans-∆2-enoyl-CoA

Third Step: Dehydrogenation

  • Enzyme: Beta-hydroxyacyl-CoA dehydrogenase
    • Converts NAD+ to NADH
    • Hydroxyl group on beta carbon is oxidized to keto group
    • Forms beta-ketoacyl-CoA

Fourth Step: Thiolysis

  • Enzyme: Thiolase
    • Cleaves bond between alpha and beta carbon
    • Produces Acetyl-CoA and a shortened fatty acyl-CoA (2 carbons less)

Yield of Beta-Oxidation

  • Single 16-carbon fatty acid produces 8 Acetyl-CoA
  • Energy Yield Calculation: NADH, FADH2, ATP counts (covered in next video)

Importance of Beta-Oxidation

  • Key process during low blood glucose levels (fasting, ketogenic diet, uncontrolled diabetes)
  • Secondary fuel source when carbohydrates are not available
  • Produces Acetyl-CoA used in Krebs cycle for ATP production via oxidative phosphorylation

Preview of Next Topics

  • Energy yield calculation from fatty acids
  • Beta-oxidation of odd-chain fatty acids
  • Beta-oxidation in peroxisomes