Peroxisomes are subcellular organelles with an indispensable role in cellular metabolism. The importance of peroxisomes for humans is stressed by the existence of a group of genetic diseases in humans in which there is an impairment in one or more peroxisomal functions. Most of these functions have to do with lipid metabolism including the alpha- and beta-oxidation of fatty acids. Here we describe the current state of knowledge about peroxisomal fatty acid alpha- and beta-oxidation with particular emphasis on the following: (1) the substrates beta-oxidized in peroxisomes; (2) the enzymology of the alpha- and beta-oxidation systems; (3) the permeability properties of the peroxisomal membrane and the role of the different transporters therein; (4) the interaction with other subcellular compartments, including the mitochondria, which are the ultimate site of NADH re-oxidation and full degradation of acetyl-CoA to CO(2) and water; and (5) the different disorders of peroxisomal alpha- and beta-oxidation.

Peroxisomes are subcellular organelles with an indispensable role in cellular metabolism. The importance of peroxisomes for humans is stressed by the existence of a group of genetic diseases in humans in which there is an impairment in one or more peroxisomal functions. Most of these functions have to do with lipid metabolism including the aand /?-oxidation of fatty acids. Here we describe the current state of knowledge about peroxisomal fatty acid aand /?-oxidation with particular emphasis on the following: (1) the substrates /?-oxidized in peroxisomes; (2) the enzymology of the aand /?-oxidation systems; (3) the permeability properties of the peroxisomal membrane and the role of the different transporters therein; (4) the interaction with other subcellular compartments, including the mitochondria, which are the ultimate site of NADH reoxidation and full degradation of acetyl-CoA to

Peroxisomes play an essential role in a number of different metabolic pathways, including the ␤-oxidation of a distinct set of fatty acids and fatty acid derivatives. The importance of the peroxisomal ␤-oxidation system in humans is made apparent by the existence of a group of inherited diseases in which peroxisomal ␤-oxidation is impaired. This includes X-linked adrenoleukodystrophy and other disorders with a defined defect. On the other hand, many patients have been described with a defect in peroxisomal ␤-oxidation of unknown etiology. Resolution of the defects in these patients requires the elucidation of the enzymatic organization of the peroxisomal ␤-oxidation system. Importantly, a new peroxisomal ␤-oxidation enzyme was recently described called Dbifunctional protein with enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase activity primarily reacting with ␣-methyl fatty acids like pristanic acid and di-and trihydroxycholestanoic acid. In this patient we describe the first case of D-bifunctional protein deficiency as resolved by enzyme activity measurements and mutation analysis. The mutation found (Gly 16 Ser) is in the dehydrogenase coding part of the gene in an important loop of the Rossman fold forming the NAD ؉ -binding site. The results show that the newly identified D-bifunctional protein plays an essential role in the peroxisomal ␤-oxidation pathway that cannot be compensated for by the L-specific bifunctional protein.