Lipid metabolism in peroxisomes: enzymology, functions and dysfunctions ofthe fatty acid alpha- and beta-oxidation systems in humans

Peroxisomes are subcellular organelles present in virtually all eukaryotic cells catalysing a number of indispensable functions in cellular metabolism . The importance of peroxisomes in man is stressed by the existence of an e xpanding group of genetic diseases in which there is an impairment in one o r more peroxisomal functions. One of the major functions of peroxisomes con cerns their role in lipid metabolism, which includes: (i) fatty acid beta-o xidation; (ii) ether phospholipid synthesis; (iii) fatty acid alpha-oxidati on; and (iv) isoprenoid biosynthesis. In this paper, we review the current state of knowledge concerning the peroxisomal fatty acid alpha- and beta-ox idation systems with particular emphasis on the enzymes involved and the va rious disorders of fatty acid oxidation in peroxisomes. We also pay attenti on to the fact that some of the metabolites that accumulate as the result o f a defect in peroxisomal alpha- and/or beta-oxidation are activators of me mbers of the family of nuclear receptors, including peroxisome-proliferator -activated receptor alpha.