Peroxisomal Metabolism

The peroxisome is a single membrane organelle present in virtually all eukaryotic cells. While the enzymatic composition and metabolic function of peroxisomes can vary from cell to cell, tissue to tissue, and organism to organism, there are a few common themes to peroxisomal metabolism in mammalian cells. First, peroxisomes catalyze the oxidation of fatty acids. In humans, peroxisomes contain two fatty acid β-oxidation pathways as well as a fatty acid β-oxidation pathway. These pathways are essential for degrading very long chain fatty acids (α. C22), 3-methyl branched-chain fatty acids, and for synthesizing bile acids. These peroxisomal pathways do not fully degrade their substrates, but instead reduce them to medium-chain length fatty acids that are exported for further α-oxidation in the mitochondrion. As for the oxidation of fuel fatty acids (e.g., palmitate, oleate), this is primarily a mitochondrial role in mammals and other animals, though peroxisomes are the sole site of all fatty acid β-oxidation in yeast and plants. Second, mammalian peroxisomal enzymes catalyze several early steps in the synthesis of ether-linked lipids. Third, inactivating mutations in the genes that code for key enzymes and transporters involved in peroxisomal α-oxidation, β-oxidation, or ether lipid synthesis cause severe neurological disorders, including X-linked adrenoleukodystrophy, D-bifunctional protein deficiency, rhizomelic chondrodysplasia punctata, and Refsum disease. Fourth, defects in peroxisome biogenesis impair all three of these core peroxisomal metabolic processes and can cause the most severe of all peroxisomal diseases, Zellweger syndrome.