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Fatty Acid Oxidation Overview and Insights

Jun 1, 2025

Lecture Notes: Fatty Acid Oxidation

Overview

  • Continuation of the discussion on fatty acid oxidation.
  • Covered beta-oxidation in tissues like the heart, muscles, and liver.
  • Focus on energy production through beta-oxidation and related pathways.

Key Concepts

Beta-Oxidation Pathway

  • Substrate: Palmitoyl-CoA (16 carbons).
  • Conversion enzyme: Fatty Acyl-CoA Synthetase.
  • Energy Requirement: Uses ATP to transform palmitate into palmitoyl-CoA.

Transport into Mitochondria

  • Enzymes:
    • CAT1 (Carnitine Palmitoyltransferase 1).
    • CAT2 (Carnitine Palmitoyltransferase 2).
  • Transport of palmitoyl carnitine into mitochondria.

Steps of Beta-Oxidation

  • Mnemonic: OHOT
    • O: Oxidation (FAD to FADH2).
    • H: Hydration (addition of water).
    • O: Oxidation (NAD+ to NADH).
    • T: Thiolysis (cleavage by thiolase, reduces chain by 2 carbons).

Energy Yield

  • From 16-carbon fatty acid (Palmitoyl-CoA):
    • Yields 8 Acetyl-CoA.
    • Each Acetyl-CoA enters TCA cycle yielding:
      • 3 NADH, 1 FADH2, 1 ATP (per Acetyl-CoA).
  • Energy Total (Rounded Calculation):
    • 31 NADH, 15 FADH2, 8 ATP.
    • Gross ATP: 131; Net ATP: 130 (after subtracting activation ATP).
    • Alternate Calculation: 108 ATP (using 2.5 and 1.5 conversion factors).

Odd-Chain Fatty Acids

  • End Product: Propionyl-CoA.
  • Involves carboxylation to Methylmalonyl-CoA (requires Biotin).
  • Conversion to Succinyl-CoA (requires Vitamin B12).
  • Pathways for Succinyl-CoA:
    • TCA Cycle (ATP production).
    • Gluconeogenesis.
    • Hemoglobin synthesis (as a precursor for porphyrins).

Peroxisomal Fatty Acid Oxidation

  • Similar Steps: Similar to mitochondrial beta-oxidation with key differences.
  • Key Reaction:
    • FAD in peroxisomes reacts with oxygen to form hydrogen peroxide (H2O2), then converted to water and oxygen by catalase.
  • Importance: Main function is processing very long chain fatty acids.

Disorders Related to Fatty Acid Oxidation

  • MCAD Deficiency:
    • Symptoms: Lipid accumulation in liver, hypoglycemia, vomiting, sleepiness, potential coma.
    • Treatment: High carbohydrate diet, frequent meals.
  • X-linked Adrenoleukodystrophy:
    • Characteristics: Affects boys under 10, causes high fatty acids in the blood, no proper fatty acid import into peroxisomes.
    • Symptoms: Visual/behavioral disturbances, coma, possible death.
  • Zellweger Syndrome:
    • Inability to form functional peroxisomes.
    • Affects fatty acid oxidation and other cellular functions.

Recap

  • Reviewed energy yield from beta-oxidation.
  • Discussed oxidation of odd chain fatty acids.
  • Addressed differences and roles of peroxisomes in oxidation.
  • Highlighted genetic disorders affecting fatty acid metabolism.

These notes aim to cover the essential insights from the lecture on fatty acid oxidation, focusing on the biochemical pathways, energy yields, and related genetic disorders.

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