In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down. See also [1].
Activation and membrane transport
1) Long-chain-fatty-acid—CoA ligase catalyzes the reaction between a fatty acid with ATP to give a fatty acyl adenylate, plus inorganic pyrophosphate, which then reacts with free coenzyme A to give a fatty acyl-CoA ester and AMP.
2) If the fatty acyl-CoA has a long chain, then the shuttle must be utilized:
a) Acyl-CoA is transferred to the hydroxyl group of carnitine by carnitine palmitoyltransferase I (see Carnitine palmitoyltransferase), located on the cytosolic faces of the outer and inner mitochondrial membranes.
b) Acyl-carnitine is shuttled inside by a carnitine-acylcarnitine translocase, as a carnitine is shuttled outside.
c) Acyl-carnitine is converted back to acyl-CoA by carnitine palmitoyltransferase II (see Carnitine palmitoyltransferase), located on the interior face of the inner mitochondrial membrane. The liberated carnitine is shuttled back to the cytosol, as an acyl-carnitine is shuttled into the matrix.
3) If the fatty acyl-CoA contains a short chain, these short-chain fatty acids can simply diffuse through the inner mitochondrial membrane.
General mechanism
Once the fatty acid is inside the mitochondrial matrix, beta-oxidation occurs by cleaving two carbons every cycle to form acetyl-CoA. The process consists of 4 steps.
1) A long-chain fatty acid is dehydrogenated to create a trans double bond between C2 and C3. This is catalyzed by acyl-CoA dehydrogenase to produce trans-delta 2-enoyl CoA. It uses FAD as an electron acceptor and it is reduced to FADH2.
2) Trans-delta2-enoyl CoA is hydrated at the double bond to produce L-3-hydroxyacyl CoA by enoyl-CoA hydratase.
3) L-3-hydroxyacyl CoA is dehydrogenated again to create 3-ketoacyl CoA by 3-hydroxyacyl CoA dehydrogenase. This enzyme uses NAD as an electron acceptor.
