The Role of Peroxisome on Zellweger Syndrome
BCHM 310
Tiffany Fong
06220576
Mitochondrial β-oxidation is responsible for the oxidation of the bulk of the short, medium and long chain Fas. However, due to the lack of acyl-CoA synthease, mitochondria cannot process the degradation of very long-chain fatty acids (>C20). Hence, in order to process these long chains it requires the peroxisomal β-oxidation system.
There are two systems in peroxisome that contributes to its breakdown of fatty acids. The first is an inducible system that is involved in the general β-oxidation process and is regulated transcriptionally by PPARα. It involves straight-chain acyl CoA oxidase (AOX), enoyl-CoA hydratase (L-PBE) and 3-ketoacyl-CoA. The second system is…show more content… Hence, one hypothesis is that peroxisome deficiency/dysfunction would lead to alterations of mitochondrial activity, which could lead to the consequences that could potentially include altered intermediary metabolism, compromised redox control, and specific deleterious effects on mitochondrial structure and function. Baumgart et al (2001) used a similar Pex5 knock out mice experiment to study this effect. They found the absence of functional peroxisomes contributed to the proliferation of pleomorphic mitochondria. The mice with a displaced PEX5 had severe alterations in their mitochondrial ultrastructure and an in increase in heterogeneity of the mitochondrial compartment in various organs and specific cell types. The mutation in the PEX5 also altered the mitochondrial respiratory chain enzymes as the mutants showed an increase of mitochondrial manganese-superoxide dismutase. They hypothesised that this alteration could lead to increased production of reactive oxygen species and this is attributed to the lack of peroxisomal antioxidant mechanisms and the accumulation of lipid intermediates of peroxisomal β-oxidation system. Baugmart et al argued that these conditions would have increased oxidative stress and contribute to the pathogenesis of multiple organ dysfunctions in Zellweger
