{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:40:31Z","timestamp":1791175231009,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,3,3]]},"abstract":"<jats:p>\n                    Peroxisomes play an essential role in a number of different metabolic pathways, including the \u03b2-oxidation of a distinct set of fatty acids and fatty acid derivatives. The importance of the peroxisomal \u03b2-oxidation system in humans is made apparent by the existence of a group of inherited diseases in which peroxisomal \u03b2-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 \u03b2-oxidation of unknown etiology. Resolution of the defects in these patients requires the elucidation of the enzymatic organization of the peroxisomal \u03b2-oxidation system. Importantly, a new peroxisomal \u03b2-oxidation enzyme was recently described called\n                    <jats:sc>d<\/jats:sc>\n                    -bifunctional protein with enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase activity primarily reacting with \u03b1-methyl fatty acids like pristanic acid and di- and trihydroxycholestanoic acid. In this patient we describe the first case of\n                    <jats:sc>d<\/jats:sc>\n                    -bifunctional protein deficiency as resolved by enzyme activity measurements and mutation analysis. The mutation found (Gly\n                    <jats:sup>16<\/jats:sup>\n                    Ser) is in the dehydrogenase coding part of the gene in an important loop of the Rossman fold forming the NAD\n                    <jats:sup>+<\/jats:sup>\n                    -binding site. The results show that the newly identified\n                    <jats:sc>d<\/jats:sc>\n                    -bifunctional protein plays an essential role in the peroxisomal \u03b2-oxidation pathway that cannot be compensated for by the\n                    <jats:sc>l<\/jats:sc>\n                    -specific bifunctional protein.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.5.2128","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:42:40Z","timestamp":1027680160000},"page":"2128-2133","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":137,"title":["Peroxisomal\n                    <scp>d<\/scp>\n                    -hydroxyacyl-CoA dehydrogenase deficiency: Resolution of the enzyme defect and its molecular basis in bifunctional protein\u2009deficiency"],"prefix":"10.1073","volume":"95","author":[{"given":"Elisabeth G.","family":"van Grunsven","sequence":"first","affiliation":[{"name":"University of Amsterdam, Academic Medical Centre, Department of Clinical Chemistry, Laboratory of Genetic Metabolic Diseases, Amsterdam, The Netherlands; Erasmus University, Sophia Children\u2019s Hospital, Department of Paediatrics, Rotterdam, The Netherlands; GSF-Forzungszentrum, Institut f\u00fcr S\u00e4ugetiergenetik, Neuherberg, D-85764 Oberschleissheim, Germany; Institute of Child Health, University of London, London WC1N 1EH, United Kingdom; Southwest Missouri State University, Department of Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel","family":"van Berkel","sequence":"additional","affiliation":[{"name":"University of Amsterdam, Academic Medical Centre, Department of Clinical Chemistry, Laboratory of Genetic Metabolic Diseases, Amsterdam, The Netherlands; Erasmus University, Sophia Children\u2019s Hospital, Department of Paediatrics, Rotterdam, The Netherlands; GSF-Forzungszentrum, Institut f\u00fcr S\u00e4ugetiergenetik, Neuherberg, D-85764 Oberschleissheim, Germany; Institute of Child Health, University of London, London WC1N 1EH, United Kingdom; Southwest Missouri State University, Department of Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lodewijk","family":"Ijlst","sequence":"additional","affiliation":[{"name":"University of Amsterdam, Academic Medical Centre, Department of Clinical Chemistry, Laboratory of Genetic Metabolic Diseases, Amsterdam, The Netherlands; Erasmus University, Sophia Children\u2019s Hospital, Department of Paediatrics, Rotterdam, The Netherlands; GSF-Forzungszentrum, Institut f\u00fcr S\u00e4ugetiergenetik, Neuherberg, D-85764 Oberschleissheim, Germany; Institute of Child Health, University of London, London WC1N 1EH, United Kingdom; Southwest Missouri State University, Department of Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vreken","sequence":"additional","affiliation":[{"name":"University of Amsterdam, Academic Medical Centre, Department of Clinical Chemistry, Laboratory of Genetic Metabolic Diseases, Amsterdam, The Netherlands; Erasmus University, Sophia Children\u2019s Hospital, Department of Paediatrics, Rotterdam, The Netherlands; GSF-Forzungszentrum, Institut f\u00fcr S\u00e4ugetiergenetik, Neuherberg, D-85764 Oberschleissheim, Germany; Institute of Child Health, University of London, London WC1N 1EH, United Kingdom; Southwest Missouri State University, Department of Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannis B. C.","family":"de Klerk","sequence":"additional","affiliation":[{"name":"University of Amsterdam, Academic Medical Centre, Department of Clinical Chemistry, Laboratory of Genetic Metabolic Diseases, Amsterdam, The Netherlands; Erasmus University, Sophia Children\u2019s Hospital, Department of Paediatrics, Rotterdam, The Netherlands; GSF-Forzungszentrum, Institut f\u00fcr S\u00e4ugetiergenetik, Neuherberg, D-85764 Oberschleissheim, Germany; Institute of Child Health, University of London, London WC1N 1EH, United Kingdom; Southwest Missouri State University, Department of Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Adamski","sequence":"additional","affiliation":[{"name":"University of Amsterdam, Academic Medical Centre, Department of Clinical Chemistry, Laboratory of Genetic Metabolic Diseases, Amsterdam, The Netherlands; Erasmus University, Sophia Children\u2019s Hospital, Department of Paediatrics, Rotterdam, The Netherlands; GSF-Forzungszentrum, Institut f\u00fcr S\u00e4ugetiergenetik, Neuherberg, D-85764 Oberschleissheim, Germany; Institute of Child Health, University of London, London WC1N 1EH, United Kingdom; Southwest Missouri State University, Department of Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh","family":"Lemonde","sequence":"additional","affiliation":[{"name":"University of Amsterdam, Academic Medical Centre, Department of Clinical Chemistry, Laboratory of Genetic Metabolic Diseases, Amsterdam, The Netherlands; Erasmus University, Sophia Children\u2019s Hospital, Department of Paediatrics, Rotterdam, The Netherlands; GSF-Forzungszentrum, Institut f\u00fcr S\u00e4ugetiergenetik, Neuherberg, D-85764 Oberschleissheim, Germany; Institute of Child Health, University of London, London WC1N 1EH, United Kingdom; Southwest Missouri State University, Department of Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T.","family":"Clayton","sequence":"additional","affiliation":[{"name":"University of Amsterdam, Academic Medical Centre, Department of Clinical Chemistry, Laboratory of Genetic Metabolic Diseases, Amsterdam, The Netherlands; Erasmus University, Sophia Children\u2019s Hospital, Department of Paediatrics, Rotterdam, The Netherlands; GSF-Forzungszentrum, Institut f\u00fcr S\u00e4ugetiergenetik, Neuherberg, D-85764 Oberschleissheim, Germany; Institute of Child Health, University of London, London WC1N 1EH, United Kingdom; Southwest Missouri State University, Department of Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean A.","family":"Cuebas","sequence":"additional","affiliation":[{"name":"University of Amsterdam, Academic Medical Centre, Department of Clinical Chemistry, Laboratory of Genetic Metabolic Diseases, Amsterdam, The Netherlands; Erasmus University, Sophia Children\u2019s Hospital, Department of Paediatrics, Rotterdam, The Netherlands; GSF-Forzungszentrum, Institut f\u00fcr S\u00e4ugetiergenetik, Neuherberg, D-85764 Oberschleissheim, Germany; Institute of Child Health, University of London, London WC1N 1EH, United Kingdom; Southwest Missouri State University, Department of Chemistry,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J. 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