Fatty Acid Oxidation Lecture Notes

Overview

• Discussion about fatty acid oxidation, focusing on energy production and pathways.
• Exploration of oxidation in peroxisomes and odd-chain fatty acids.

Beta Oxidation Process

• Palmitoleic Acid: 16-carbon fatty acid.

  • Converted into palmitoyl-CoA using fatty acyl-CoA synthetase.
  • ATP is broken down to ADP + inorganic phosphate to provide energy for this conversion.

• Transporters:

  • CAT1/Carnitine Palmitoyltransferase 1: Adds carnitine, removes CoA.
  • CAT2/Carnitine Palmitoyltransferase 2: Recycles carnitine, adds CoA back.

Beta Oxidation Steps

• Mnemonic OHOT:
  • Oxidation: FAD to FADH2.
  • Hydration: Addition of water.
  • Oxidation: NAD+ to NADH.
  • Thiolysis: Fatty acyl-CoA shortened by 2 carbons, producing acetyl-CoA.
• Cycles through 7 rounds.
• Total ATP yield from one 16-carbon fatty acid can be 130 ATP (gross), accounting for the ATP required to activate the fatty acid.

Energy Production Calculation

• Acetyl CoA Production:
  • 8 acetyl-CoA from a 16-carbon fatty acid.
  • Each acetyl-CoA enters Krebs cycle:
    • Produces 3 NADH, 1 FADH2, 1 ATP.
• Resulting ATP Calculation:
  • 31 NADH x 3 ATP = 93 ATP
  • 15 FADH2 x 2 ATP = 30 ATP
  • Plus 8 ATP from substrate-level phosphorylation = 131 ATP (gross).
  • Subtract 1 ATP used in activation = 130 ATP net.

Odd-chain Fatty Acid Oxidation

• Odd-chain fatty acids result in propionyl-CoA (3-carbons).

• Conversion through Carboxylation:

  • Propionyl-CoA Carboxylase: Requires ATP, biotin.
  • Converts propionyl-CoA to methylmalonyl-CoA, then to succinyl-CoA.

• Fates of Succinyl-CoA:

  • Gluconeogenesis: Converts to oxaloacetate, then to glucose.
  • ATP Production: Continues through Krebs cycle.
  • Heme Synthesis: Precursor for porphyrins.

Oxidation in Peroxisomes

• Functions similarly to mitochondria but differs mainly in the first step.
• First Step:
  • Fatty acyl-CoA reacts with O2 and water, converting FADH2 to H2O2.
  • Catalase: Breaks down H2O2 to water and O2 to prevent damage.

Disorders

• MCAD Deficiency:

  • Medium-chain acyl-CoA dehydrogenase deficiency.
  • Symptoms: Lipid accumulation in liver, hypoglycemia, vomiting, sleepiness, coma.
  • Management: High-carb diet, frequent meals.

• X-linked AdrenoLeukoDystrophy:

  • Defect in transporter for fatty acids into peroxisomes.
  • Symptoms: High fatty acids in blood, visual/behavioral disturbances, coma.

• Zellweger Syndrome:

  • Inability to form functional peroxisomes.
  • Causes multiple systemic effects.