Peroxisomal D-hydroxyacyl-CoA dehydrogenase deficiency: resolution of the enzyme defect and its molecular basis in bifunctional protein deficiency
| Autor: | R. J. A. Wanders, E. G. van Grunsven, E. van Berkel, Jerzy Adamski, Peter E. Clayton, J. B. C. De Klerk, Lodewijk IJlst, Dean Cuebas, Hugh Lemonde, Peter Vreken |
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| Přispěvatelé: | Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Male
Pristanic acid 17-Hydroxysteroid Dehydrogenases Glycine Biology Microbodies Polymerase Chain Reaction chemistry.chemical_compound Fatal Outcome Peroxisomal Multifunctional Protein-2 Multienzyme Complexes Serine medicine Humans Point Mutation Abnormalities Multiple Enoyl-CoA Hydratase Peroxisomal targeting signal Cells Cultured Hydro-Lyases DNA Primers Skin D-bifunctional protein deficiency Binding Sites Multidisciplinary Base Sequence 3-Hydroxyacyl CoA Dehydrogenases Brain Infant Biological Sciences Enoyl-CoA hydratase Peroxisome medicine.disease Magnetic Resonance Imaging Molecular biology 3-Hydroxyacyl-CoA Dehydrogenase Biochemistry chemistry Female Adrenoleukodystrophy |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, 95(5), 2128-2133. National Academy of Sciences |
| ISSN: | 0027-8424 |
| Popis: | Peroxisomes play an essential role in a number of different metabolic pathways, including the β-oxidation of a distinct set of fatty acids and fatty acid derivatives. The importance of the peroxisomal β-oxidation system in humans is made apparent by the existence of a group of inherited diseases in which peroxisomal β-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 β-oxidation of unknown etiology. Resolution of the defects in these patients requires the elucidation of the enzymatic organization of the peroxisomal β-oxidation system. Importantly, a new peroxisomal β-oxidation enzyme was recently described called d -bifunctional protein with enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase activity primarily reacting with α-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 β-oxidation pathway that cannot be compensated for by the l -specific bifunctional protein. |
| Databáze: | OpenAIRE |
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