Fat Catabolism-part3

Free Fatty Acids: Metabolism and Utilization

  • Free fatty acids released into the bloodstream are absorbed by cells, particularly in the liver and skeletal muscle.

  • Triglycerides break down into fatty acids, which have several fates:

    • Used in the synthesis of membrane lipids crucial for cell membrane integrity.

    • Utilized for energy through beta oxidation, generating FADH2 and NADH.

Beta Oxidation

  • Beta Oxidation Process:

    • Produces Acetyl CoA, which can enter the citric acid cycle to generate more electron carriers.

    • Both beta oxidation and citric acid cycle yield ATP through the oxidation of fatty acids.

    • Acetyl CoA can also contribute to cholesterol biosynthesis and be converted to ketone bodies.

Lipid Digestion and Absorption

  • Lipids from the diet converted to monoacylglycerol and fatty acids for absorption into tissues like muscle, liver, and adipose tissue.

  • Key sites for utilization of fatty acids are primarily liver and muscle due to their roles in energy harvesting and storage.

Conversion to Acyl CoA

  • The initial step in beta oxidation involves converting fatty acids into acyl CoA:

    • Requires ATP and an enzyme known as acyl CoA synthetase.

    • Different chain lengths require specific acyl CoA synthetases.

    • ATP is hydrolyzed to AMP and pyrophosphate (PPi) to drive the reaction forward via formation of an acyl adenylate intermediate.

    • Coenzyme A is incorporated to form acyl CoA, releasing AMP.

Transport into Mitochondria

  • Formation of acyl CoA occurs in the cytosol; subsequent reactions occur in the mitochondrial matrix.

  • Carnitine Transferase System:

    • Facilitates transport of fatty acyl CoA into the mitochondrial matrix.

    • Components include:

      • Carnitine palmitoyltransferase I (CPT I) on the cytosolic side.

      • Carnitine palmitoyltransferase II (CPT II) on the matrix side.

      • Carnitine carrier protein (integral membrane protein).

Steps of Beta Oxidation Cycle

  1. Conversion to Enoyl CoA:

    • First reaction catalyzed by acyl CoA dehydrogenase leading to the formation of trans delta 2 enoyl CoA, producing reduced FAD.

  2. Hydration:

    • Enoyl CoA is converted to hydroxyacyl CoA through the action of hydratase, adding a water molecule across the double bond.

  3. Dehydrogenation to Ketone:

    • Hydroxyacyl CoA is converted to beta-ketoacyl CoA by another dehydrogenase, consuming NAD+ and producing NADH.

  4. Cleavage to Acetyl CoA:

    • Final step cleaves beta-ketoacyl CoA to release Acetyl CoA and produce a fatty acyl CoA that is two carbons shorter than the original.

Outcome of Beta Oxidation

  • Each cycle of beta oxidation reduces the fatty acid chain by 2 carbons and produces Acetyl CoA, which can enter the citric acid cycle for further energy production.

  • Palmitoyl CoA (C16) can generate 8 Acetyl CoA molecules through successive cycles of beta oxidation.