Chapter 17 Fatty Acid Catabolism

Fatty Acid Catabolism Overview

  • Focus on the process of breaking down fatty acids into Acetyl-CoA for energy production.

Acyl CoA and Components

  • Acyl CoA: Activated fatty acids (like Palmitoyl CoA) serve as substrates.

  • Key Enzymes:

    • Dehydrogenase - catalyzes oxidation.

    • Hydratase - adds water to double bonds.

    • Thiolase - facilitates the cleavage of Acyl groups.

  • Energy Carriers: FAD, FADH2, NAD, and NADH are involved in oxidation processes.

Metabolic Pathways

  • Two primary pathways:

    • Catabolism (breaking down fatty acids for energy).

    • Anabolism (synthesizing fatty acids; occurs predominantly in the fed state).

Types of Lipids

  • Phospholipids and Triacylglycerols (TAGs): Store energy and form cellular structures.

  • TAGs composed of glycerol and three fatty acids in ester linkage.

  • TAGs provide more energy compared to carbohydrates (2x).

Pathway of Fatty Acid Catabolism

  1. Digestion and transport of dietary fats

  2. Mobilization of stored fats from adipose tissue

  3. Activation of fatty acids to Acyl-CoA

  4. Transport of activated fatty acids into mitochondria

  5. Beta-oxidation of fatty acids to generate Acetyl-CoA

  6. Acetyl-CoA enters citric acid cycle (CAC)

  7. Electrons from CAC enter electron transport chain (ETC) for ATP production

Dietary Sources and Metabolism

  • Sources: Dietary fats, carbohydrates, proteins (like glycogen, glucose, alanine).

  • Transport: Via chylomicrons and lipoproteins from intestines through lymph and blood to tissues.

Activation of Fatty Acids

  • Enzymatic process converts fatty acids into Acyl-CoA (requires ATP).

  • Fatty Acyl-CoA then transferred into mitochondria using the carnitine shuttle.

Beta-Oxidation Process

  • Takes place in mitochondrial matrix.

  • Involves four steps: oxidation, hydration, second oxidation, and thiolysis.

  • Each cycle shortens the fatty acid chain by two carbons, producing Acetyl-CoA.

  • The process produces FADH2 and NADH, which are pivotal for ATP synthesis.

  • Special adaptations for unsaturated fatty acids with double bonds.

Energy Yield

  • Total ATP Yield from Palmitoyl-CoA oxidation: 106 ATP (net yield after activation costs).

  • Fatty acid oxidation produces more ATP than glucose breakdown due to energy density.

Regulation of Fatty Acid Metabolism

  • Fasting State: Increased lipolysis releases free fatty acids for energy use over glucose.

  • Fed State: Presence of glucose leads to fatty acid synthesis; malonyl-CoA inhibits entry of fatty acids into mitochondria.

  • Hormonal Influence: Insulin promotes storage; glucagon and epinephrine promote mobilization of fatty acids.

Genetic Disorders

  • Disorders such as Medium-Chain Acyl-CoA Dehydrogenase (MCAD) deficiency lead to fatty acids' accumulation and hypoglycemia.

Ketone Bodies Production

  • Occurs from excessive fatty acid breakdown (particularly during starvation or uncontrolled diabetes).

  • Ketone bodies (like Acetoacetate and D-B-hydroxybutyrate) can be used by tissues like heart and brain as an alternative fuel.

  • Ketoacidosis: Dangerous condition if ketone body levels become excessively high, lowering blood pH.