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?