Lecture on Fatty Acid Oxidation

Introduction

• Focus on fatty acid oxidation.
• Previous knowledge of the mobilization of fat is beneficial.
• Mobilization involves breaking triglycerides into glycerol and fatty acids.
• Main tissues utilizing fatty acids: Heart muscle, skeletal muscles, and liver.
  • Liver is key for generating ketone bodies.

Fatty Acid Entry into Cells

• Fatty acids are transported into tissue cells.
• Example: Long chain fatty acids (e.g., Palmitic acid - 16 carbons).
• Fatty acids need transformation to stay in the cell and enter the mitochondria.

Activation of Fatty Acids

• Enzyme: Fatty acyl-CoA synthetase.
  • Converts free fatty acids to fatty acyl-CoA.
  • Requires ATP, which is converted to ADP and inorganic phosphate.
• Result: Formation of fatty acyl-CoA.

Transport into Mitochondria

• Problem: Fatty acyl-CoA cannot enter mitochondria directly.
• Solution: Conversion to fatty acyl carnitine.
  • Enzyme: Carnitine acyl transferase 1 (CAT1) or carnitine palmitoyltransferase 1 (CPT1).
  • Process: Combines fatty acyl-CoA with carnitine, releasing CoA.
• Transport: Fatty acyl carnitine moves into mitochondria via translocase.
• Re-conversion inside mitochondria:
  • Enzyme: Carnitine acyl transferase 2 (CAT2) or carnitine palmitoyltransferase 2 (CPT2).
  • Process: Removes carnitine, adds CoA back to fatty acyl group.

Beta Oxidation

• Converts fatty acyl-CoA into acetyl-CoA units.

• Process involves four main steps:

  Step 1: Dehydrogenation

  • Enzyme: Acyl-CoA dehydrogenase.
  • Produces FADH2 by removing hydrides.
  • Forms trans double bond between alpha and beta carbons.

  Step 2: Hydration

  • Enzyme: Enoyl-CoA hydratase.
  • Adds water across the double bond.
  • Produces beta-hydroxyacyl-CoA.

  Step 3: Oxidation

  • Enzyme: Beta-hydroxyacyl-CoA dehydrogenase.
  • Converts NAD+ to NADH.
  • Forms beta-ketoacyl-CoA by creating a ketone at the beta carbon.

  Step 4: Thiolysis

  • Enzyme: Thiolase.
  • Cleaves bond between alpha and beta carbon.
  • Releases acetyl-CoA and a shortened fatty acyl-CoA.

Importance of Beta Oxidation

• Provides acetyl-CoA for the Krebs cycle, generating NADH, FADH2, and ATP.
• Backup energy source when blood glucose levels are low (fasting, ketogenic diet, diabetes).

Calculating Production

• A 16-carbon fatty acid yields 8 acetyl-CoAs.
• Rounds of Beta Oxidation: 7 (one less than the number of acetyl-CoAs produced).

Next Steps

• Future discussions on energy yield, odd-chain fatty acid oxidation, and beta oxidation in peroxisomes.