Fatty Acid Oxidation (Beta Oxidation)

Overview

• Beta oxidation is the breakdown of fatty acids into acetyl CoA, which forms ketones and other metabolic fuels.
• Provides energy primarily to the liver, forming ketone bodies used by the brain and muscles.

Fatty Acid Sizes and Oxidation Locations

• Short/Medium Chain Fatty Acids: 2-12 carbons
  • Oxidized in mitochondria.
• Long Chain Fatty Acids: 14-20 carbons
  • Require carnitine transport into mitochondria.
• Very Long Chain Fatty Acids: >20 carbons
  • Oxidized in peroxisomes.

Memorization Technique

• Relate the number of carbons to school age and study duration:
  • 2-12 carbons: Elementary school (short/medium study time)
  • 14-20 carbons: High school/college (long study time)
  • >20 carbons: Medical school (very long study time)

Carnitine Transport System

• Precedes beta oxidation for long-chain fatty acids.
• Steps:
  1. Fatty acid converted to fatty acyl CoA by fatty acyl CoA synthetase.
  2. Fatty acyl CoA converted to fatty acyl carnitine by carnitine acyltransferase 1 (CAT-1).
  3. Fatty acyl carnitine enters mitochondria, converted back to fatty acyl CoA by CAT-2.
• Inhibition:
  • Malonyl CoA inhibits CAT-1, preventing fatty acid breakdown when synthesis is active (feedback mechanism).

Beta Oxidation

• Fatty acyl CoA converted to acetyl CoA by fatty acyl CoA dehydrogenase.
  • Enzyme names vary by chain length (medium/long).
• Products:
  • Ketone bodies (in liver during starvation)
  • Acetyl CoA enters TCA cycle for ATP production.

Key Enzymes and Inhibitors

• Rate-limiting Enzyme: CAT-1
  • Mnemonics: "Carnage of Fatty Acids", C-A-T loves fatty acids (tuna).
• Inhibitor: Malonyl CoA

Related Diseases

1. Systemic Primary Carnitine Deficiency
   • Problem: Can't transport fatty acyl CoA into mitochondria.
   • Symptoms: Hypoketotic hypoglycemia.
2. Myopathic CAT-2 Deficiency
   • Problem: CAT-2 enzyme deficiency.
   • Symptoms: Myoglobinuria, hypotonic/weak muscles, increased muscle triglycerides, rhabdomyolysis.
   • Indicators: Dark urine, elevated CK, increased creatinine.
3. Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCAD)
   • Problem: Deficiency in enzyme breaking down medium-chain fatty acyls.
   • Symptoms: Non-ketotic hypoglycemia, hepatic dysfunction, hyperammonemia.
   • Treatment: Avoid fasting, increase carbohydrate intake.

Conclusion

• Fatty Acid Oxidation = Carnitine Shuttle + Beta Oxidation.
• Essential for understanding energy mobilization and metabolic pathways.