135 5 Establishing a peroxisomal β-oxidation computational kinetic model to understand the effects of amino-acid restriction to the electron transport chain, is located on a face of the flavin ring normally shielded in ACOX132. These two factors can potentially explain why the FADH 2 in acyl-CoA oxidases donates the electrons directly to molecular oxygen and not the ETC. Several groups have characterized ACOX1 and measured its kinetic properties, either using the isolated enzyme or peroxisomal fractions9,27. Most groups found Km values for acyl-CoAs with 14-18 carbon atoms (C14-C18) to be very similar between them and lower than those found for shorter substrates (C8 to C4). These results emphasize the preference of ACOX1 for longer chain fatty acids. Vmax values were relatively similar for most chain lengths ranging from C8 to C16, values were relatively similar for most chain lengths ranging from C8 to C16, with the highest value for C1633. Different groups also reported similar values of the Km for oxygen9,27 . No information about the K m for H2O2 was found. However, given that the enzyme is virtually irreversible, product inhibition by H2O2 is probably negligible. The enzyme was reported to be inhibited by CoA by Hovik et al34, in line with previous observations in which CoA inhibited β-oxidation of acyl-CoA esters34. Acetyl-CoA was also reported to be an inhibitor of the enzyme, yet no Ki values were reported34. Interestingly, the enzyme was also inhibited by 3-ketohexadecanoyl-CoA. This inhibition was thought to be relevant for regulation of the pathway as the Km of the downstream ACAA1 enzyme for 3-ketohexadecanoy-CoA was found to be several times higher than the Ki of ACOX1 for the same compound27. The authors did not specify the putative impact of such regulation. We may speculate, however, that a strong feedback inhibition of ACOX1 by 3-ketohexadecanoy-CoA would prevent overloading the pathway, well before ACAA1 is saturated. Catalase Hydrogen peroxide, produced by peroxisomal oxidases including ACOX1, is a reactive oxygen species that can lead to cellular damage at high concentrations35. Catalase is an important enzyme in the peroxisome, in charge of degrading hydrogen peroxide back into molecular oxygen and water36. High levels of H2O2 in the peroxisome can modify the last enzyme of the peroxisomal β-oxidation (3-ketoacyl-CoA thiolase) as well as its substrate acetoacetyl-CoA37. Therefore, the presence of catalase is of clear importance in the peroxisome in order to avoid H2O2 accumulation. Kinetic properties of catalase from different organisms, including bovine liver, human erythrocytes and many bacterial strains, have been extensively studied38. Several groups have isolated and characterized catalase, and
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