期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：5
页码：2128-2133
DOI：10.1073/pnas.95.5.2128
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Peroxisomes play an essential role in a number of different metabolic pathways, including the {beta}-oxidation of a distinct set of fatty acids and fatty acid derivatives. The importance of the peroxisomal {beta}-oxidation system in humans is made apparent by the existence of a group of inherited diseases in which peroxisomal {beta}-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 {beta}-oxidation of unknown etiology. Resolution of the defects in these patients requires the elucidation of the enzymatic organization of the peroxisomal {beta}-oxidation system. Importantly, a new peroxisomal {beta}-oxidation enzyme was recently described called D-bifunctional 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 (Gly16Ser) 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 {beta}-oxidation pathway that cannot be compensated for by the L-specific bifunctional protein.
