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Fatty Acid Oxidation Lecture

Jun 16, 2024

Fatty Acid Oxidation Lecture

Introduction

In this lecture, we continue discussing fatty acid oxidation. The previous part covered beta oxidation in tissues like the heart, muscles, and liver. Today's focus will include:

  • Energy production from beta oxidation
  • Mnemonics to remember steps in beta oxidation
  • Oxidation in peroxisomes and odd-chain fatty acids

Beta Oxidation Summary

Steps and Mnemonic (OHOT):

  1. Oxidation
    • FAD to FADH₂
    • Generates trans-Δ²-enoyl-CoA
  2. Hydration
    • Adds H₂O, forming β-hydroxyacyl-CoA
  3. Oxidation
    • NAD⁺ to NADH, forming β-ketoacyl-CoA
  4. Thiolysis
    • Splits into shorter acyl-CoA and acetyl-CoA
    • Each cycle removes 2-carbon acetyl-CoA unit

Energy Production Calculation:

  • From a 16-carbon fatty acid (Palmitoyl CoA):
    • 8 acetyl-CoA (16 carbons / 2)
    • Per acetyl-CoA in Krebs Cycle: 3 NADH, 1 FADH₂, 1 ATP
    • Total: 8 acetyl-CoA = 24 NADH, 8 FADH₂, 8 ATP
      • 7 NADH + 7 FADH₂ from beta oxidation
    • Overall: 31 NADH × 3 ATP/NADH = 93 ATP, 15 FADH₂ × 2 ATP/FADH₂ = 30 ATP, + 8 ATP = 131 ATP gross (130 net after subtracting activation energy)

Odd-Chain Fatty Acid Oxidation

  • End product propionyl-CoA requires special processing
  • Propionyl-CoA Carboxylase (requires biotin) adds a carbon to form methylmalonyl-CoA
  • Methylmalonyl-CoA mutase (requires vitamin B12) forms succinyl-CoA
  • Succinyl-CoA can:
    • Enter Krebs cycle for ATP production
    • Convert to oxaloacetate for gluconeogenesis
    • Form heme and porphyrins for hemoglobin

Peroxisomal Fatty Acid Oxidation

  • Peroxisomes handle very long-chain fatty acids
  • First step differs from mitochondria:
    • Uses FADH₂ to generate H₂O₂ (hydrogen peroxide) instead of transferring electrons directly to the electron transport chain
    • Catalase breaks down H₂O₂ into water and oxygen

Disorders in Fatty Acid Oxidation

  1. MCAD Deficiency (Medium-Chain Acyl-CoA Dehydrogenase Deficiency)
    • Enzyme deficient: medium-chain acyl-CoA dehydrogenase
    • Symptoms: Lipid accumulation in liver, hypoglycemia, vomiting, sleepiness, coma
    • Treatment: High-carb diet, frequent meals
  2. X-linked Adrenoleukodystrophy (X-ALD)
    • Deficiency in peroxisomal transporter
    • Symptoms: High fatty acids in blood, visual disturbances, behavioral changes, coma, and death
    • Affects boys under 10
  3. Zellweger Syndrome
    • Inability to create functional peroxisomes
    • Multisystemic impacts

Conclusion

  • Reviewed beta oxidation and energy tally
  • Discussed odd-chain fatty acid oxidation and succinyl-CoA roles
  • Highlighted peroxisomal oxidation
  • Covered significant disorders: MCAD deficiency, X-ALD, Zellweger Syndrome

Note: Energy yield calculation may vary slightly in literature due to different NADH and FADH₂ ATP equivalents.

Full transcript