The role of peroxisomes in glycerol ether lipid metabolism

Peroxisomes (microbodies) are ubiquitous subcellular organelles whose functions in cellular metabolism are not clear. In recent years peroxisomes have been shown to play roles in the oxidation of long chain fatty acids and ether lipid biosynthesis. The key enzymes of the acyl DHAP pathway i.e. DHAP acyltransferase and alkyl DHAP synthase have been shown to be localized in peroxisomes indicating that these organelles are obligatory for the biosynthesis of cellular glycerol ether lipids. This is proved by the discovery that in the tissues of patients suffering from Zellweger cerebrohepatorenal syndrome, an autosomal recessive disorder where peroxisomes are known to be absent, the acyl DHAP pathway enzymes and the ether lipids were also found to be deficient. Based on such biochemical abnormalities a number of similar genetic disorders such as neonatal adrenoleukodystrophy, different forms of chondrodysplasia punctata, infantile Refsum disease etc. have been characterized as peroxisomal deficiency disorders. These and other findings show that peroxisomes have a regulatory role in membrane lipid biogenesis. It seems that the main role of peroxisomes is to compartmentalize biochemical reactions which cannot proceed in other cellular organelles either due to formation of toxic product (H2O2) or due to non-availability of crucial metabolite (DHAP). The products of the reactions catalyzed by the peroxisomal enzymes e.g. acetyl CoA or alkyl DHAP are then transported out from peroxisomes to other cellular compartments where they are utilized to produce fatty acids, cholesterol, glycerol ether lipids etc. for membrane biogenesis.