In addition to the beta-oxidation of fatty acids in mitochondria, animal cells carry out beta-oxidation in another organelle, the peroxisome. Although the mitochondrial and peroxisomal beta-oxidation pathways are similar, the details differ somewhat. Plants conduct beta-oxidation entirely in peroxisomes and glyoxysomes. Both pathways result in the progressive oxidation and release of two carbon acetyl groups from fatty acids. Although the enzymes involved in both pathways are somewhat different, the chemical transformations of the fatty acids are the same in both. The first difference between the pathways is that the initial substrate in peroxisomes is very long chain fatty acids, longer than those that mitochondria can efficiently oxidize. There is no transport system required for very long chain fatty acids to enter peroxisomes, since they are able to diffuse in. In both pathways fatty acids are activated by the addition of Coenzyme A. In mitochondria, the first reaction of the pathway forms reduced FADH2 that carries high-energy electrons to the electron transport chain, helping to drive ATP synthesis. In peroxisomes, the first step uses FAD as a cofactor, but does not produce FADH2 and does not contribute to ATP production. Instead, hydrogen peroxide is formed, which is then converted to water and oxygen by the enzyme catalase. The lack of ATP generation in peroxisomes at this step makes peroxisomal beta-oxidation a less efficient energy source than the mitochondrial pathway. The remaining enzymes of the two pathways are distinct proteins from different genes, although they catalyze the same reactions. The NADH produced in the peroxisomal pathway is exported from the organelle, long with acetyl-CoA produced, while in mitochondria these remain in the matrix to contribute further to energy production through the Krebs Cycle and oxidative phosphorylation. Once the fatty acid chains are reduced in length in the peroxisomal pathway, they are conjugated to carnitine and leave the peroxisome to be transported into mitochondria for further oxidation to acetyl-CoA.
Individuals lacking the pathway demonstrate the importance of peroxisomal beta-oxidation. In people without the enzyme that forms the CoA esters with very long chain fatty acids in peroxisomes, very long chain fatty acids accumulate in the blood and lead the degradation of the myelin sheath of nerves. This condition was depicted in the film Lorenzo's Oil.
