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Summary of Lipid Metabolism

OXIDATION OF SATURATED : β- oxidation
Beta-oxidation is the process by which fatty acids, in the form of acyl-CoA molecules, are broken down in mitochondria and/or peroxisomes to generate acetyl-CoA, the entry molecule for the citric acid cycle.

The oxidation of fatty acids involve three stages:
  1. Activation of fatty acids in the cytosol
  2. Transport of activated fatty acids into mitochondria (carnitine shuttle)
  3. Beta oxidation proper in the mitochondrial matrix

Once the fatty acids have been transported to the mitochondrial matrix via carnitine pathway, β-oxidation of fatty acyl-CoA (n carbons) occurs within the mitochondria in four steps as discussed below :
  1. First step - Fatty acyl-CoA is acted upon by an enzyme acyl-CoA dehydrogenase which is FAD dependent. Fatty acyl-CoA undergoes dehydrogenation and forms a trans-double bond at the α and β carbons to form trans-Δ2-enoyl-CoA. Acyl-CoA dehydrogenase are present as three isoenzymes each specific for a particular carbon chain length (short, intermediate and long). The electrons which were removed from the fatty acyl-CoA chain are transferred to FAD which gets reduced to FADH2. This FADH2 immediately via the Electron Transport System gets converted to ATP molecules.

  2. Second step - Enoyl-CoA hydratase catalyzes this reaction where water is added. Hydration occurs at the double bond resulting in the formation of β-hydroxyacyl-CoA.

  3. Third step - β-hydroxyacyl-CoA undergoes dehydrogenation to form β-ketoacyl-CoA in the presence of β-hydroxyacyl-CoA dehydrogenase. The electrons available as a result of dehydrogenation are accepted by NAD+ to form NADH + H+ which immediately exchanges these electrons with oxygen in the Electron Transport System to form ATP molecules.

  4. Fourth step - This reaction is called as thiolysis as acyl-CoA acetyltransferase (also known as thiolase) in the presence of CoA-SH causes the cleavage of β-ketoacyl-CoA to form acetyl CoA and the thioester of the original fatty acid with two carbons less. This cleavage occurs as the β carbon ketone group is a good target for nucleophilic attack by the thiol (-SH) group of the coenzyme A.

The new fatty acyl-CoA (n-2 carbons) formed again participates in the β-oxidation cycle to form a new fatty acyl-CoA with two carbons less (n-4 carbons) and a new molecule of acetyl CoA. This process continues till the entire fatty acid is converted into acetyl CoA molecules.