Beta-oxidation is an ubiquitous function present in virtually all eukaryotic organisms. It involves the breakdown of long-chain fatty acids (FAs), long-chain dicarboxylic acids, eicosanoids and bile acids, but here we will focus on the breakdown of long-chain FAs. The pathway generally consists of four reactions: dehydrogenation, hydration, dehydrogenation again and lastly, a thiolytic cleavage. Peroxisomal beta-oxidation is important as it is the only means by which the body can metabolise long chain or very long chain fatty acids over 20 carbons in length, as the pathway present in mitochondria is unable to do so (Reddy 2001).
Before FAs can undergo beta-oxidation it must be activated by being joined to acetyl CoA, this is done so by Acyl-CoA synthase which can be found in the membrane of peroxisomes. The diagram below shows an overview of the enzymes involved in PPARα-ligand inducible beta-oxidation: |
Image from Reddy (2001)
The figure above shows the two core beta-oxidation pathways that are present in peroxisomes. The inducible pathway describes the system that is regulated and inducible by PPARα that is responsible for metabolising straight chain FAs, with the initial step being catalysed by straight chain acyl-CoA oxidase (AOX), then enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase [otherwise known as L-bifunctional protein (L-PBE)], and finally 3-ketoacyl-CoA thiolase, resulting in the removal of 2 carbons from the long chain FA via acetyl-CoA (Mannaaerts 2000). This cycles until the FA can complete oxidation and can be transported and metabolised by the mitochondria.The non-inducible pathway whose initial step is catalysed by branched-chain acyl-CoA oxidase (BOX) is responsible for metabolising long-branched-chain fatty-acyl CoAs. The figure also shows that after initial specifc enzyme catalysis, products are not restricted to a single pathway, but rather both pathways contain enzymes that are able to metabolise any products after the first dehydrogentation, this is known as cross-talking.
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