Peroxisomal lipid metabolism.

Peroxisomes are present in virtually all eukaryotic cells. At present, they are known to contain more than 50 enzymes, more than half of which play a role in lipid metabolism. During the past two decades, considerable knowledge has been gained about the role of peroxisomes in lipid metabolism, the implications of induction of hepatic peroxisome proliferation and the peroxisomal fatty acid beta-oxidation enzyme system in the development of hepatocellular carcinomas in rats and mice by structurally diverse groups of chemicals designated as peroxisome proliferators, and the biochemical basis for inheritable diseases in humans caused by disturbances and/or deficiencies in peroxisomal lipid metabolism. Nevertheless, many unanswered questions remain. The ontogeny and homeostatic interrelationships between the enzymes of the peroxisomal and mitochondrial lipid metabolism have yet to be fully elucidated. The mechanism(s) by which PPARs are activated also remains unclear. Information about the interplay between PPAR, RXR alpha, HSP72, and other possible regulatory molecules is necessary to elucidate the transcriptional activation of inducible peroxisomal genes. The assumption that multiple signaling pathways may be responsible for the pleiotropic responses induced by structurally different peroxisome proliferators requires further examination. Finally, studies to identify and characterize different PPARs and PPREs from inducible peroxisomal genes from a variety of species are also required for a clear understanding of the role of peroxisomal beta-oxidation enzyme system in the pathogenesis of hepatocellular carcinogenesis induced by peroxisome proliferators.