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Fatty Acid Oxidation Detailed Notes

Major Energy Sources

  • Fats
  • Carbohydrates
  • Proteins
  • Main metabolic path includes glucose, fatty acids, and amino acids leading to Acetyl-CoA, then the citric acid cycle, oxidative phosphorylation, and ATP production.

Triacylglycerol (TAG) Overview

  • Composition: Glycerol and three fatty acids.
  • Storage: Primary storage form of lipids in adipose tissue (adipocytes).
  • Characteristics: Hydrophobic and tightly packed.

Mobilization of Fatty Acids

  • Lipolysis: TAG is broken down into free fatty acids and glycerol by lipase.
  • Transport: Fatty acids (insoluble) are transported in the bloodstream by the protein albumin.

Fatty Acid Oxidation: Overview

  • Occurs in mitochondria with three main compartments: Outer membrane, Inner membrane, and Matrix.
  • Steps include:
    • Activation of fatty acids
    • Transport into mitochondrial matrix
    • Breakdown via β-oxidation

Activation of Fatty Acids

  • Enzyme: Acyl-CoA synthase catalyzes the attachment of Coenzyme A to fatty acids on the outer mitochondrial membrane.
  • Reaction: ATP is converted to AMP.

Transport of Acyl-CoA into Matrix

  • Enzymes:
    • Carnitine acyltransferase I & II involved in the transport of acyl-CoA across the mitochondrial membranes.
    • Carnitine is essential for transport to the mitochondrial matrix.

β-Oxidation Process

  1. Oxidation: Acyl-CoA is oxidized by acyl CoA dehydrogenase, producing FADH2.
  2. Hydration: Enoyl CoA hydratase adds water to form 3-Hydroxyacyl CoA.
  3. Oxidation: 3-Hydroxyacyl CoA is oxidized to 3-Ketoacyl CoA, producing NADH.
  4. Cleavage: 3-Ketoacyl CoA is cleaved by β-ketothiolase to yield Acetyl CoA and shortened acyl-CoA.
  • Products: Each round of β-oxidation results in:
    • 1 Acetyl CoA
    • 1 FADH2
    • 1 NADH

Summary of Fatty Acid Metabolism

  • Mobility and Activation: TAG stored in adipocytes, mobilized by lipase, transported by albumin, activated by ATP to form Acyl-CoA.
  • Translocation into Matrix: Requires carnitine for transport into the mitochondrial matrix for breakdown.
  • Oxidation Steps: Sequential oxidation, hydration, oxidation, and cleavage produce Acetyl-CoA, with energy carriers FADH2 and NADH.

Breakdown of Specific Fatty Acids

  • Even number carbon fatty acids: typical β-oxidation.
  • Odd number carbon fatty acids require extra steps for complete breakdown (e.g., propionyl-CoA conversion).
  • Unsaturated fatty acids introduce isomerization steps.

Ketone Bodies

  • Produced in the liver from Acetyl-CoA during low glucose conditions (e.g., fasting).
  • Key types: Acetoacetate, Acetone, and Hydroxybutyrate.
  • Serve as an alternative fuel source, particularly for the brain during prolonged fasting or carbohydrate-restricted diets (e.g., ketogenic diet).

Important Questions to Consider

  • Where are fatty acids stored and in what form?
  • What mechanisms mobilize and transport fatty acids for oxidation?
  • What are the four steps of β-oxidation, and where are FADH2 and NADH produced?
  • What enzyme catalyzes the final β-oxidation step?
  • What reactions are specific to odd-numbered or unsaturated fatty acids?
  • How and when is ketone body production relevant?