Peroxisomal fatty acid beta-oxidation in relation to the accumulation of very long chain fatty acids in cultured skin fibroblasts from patients with Zellweger syndrome and other peroxisomal disorders
| Autor: | H. van den Bosch, AndréW. Schram, R. J. A. Wanders, C. W. T. van Roermund, Judith C. Heikoop, Joseph M. Tager, M.J.A. van Wijland, Ruud B.H. Schutgens |
|---|---|
| Přispěvatelé: | Other departments |
| Rok vydání: | 1987 |
| Předmět: |
medicine.medical_specialty
Coenzyme A Palmitates Biology Fatty acid beta-oxidation Microbodies Facial Bones chemistry.chemical_compound Internal medicine Peroxisomal disorder medicine Humans Skin chemistry.chemical_classification Polycystic Kidney Diseases Zellweger syndrome Fatty Acids Skull Fatty acid Syndrome General Medicine Peroxisome medicine.disease Endocrinology Biochemistry chemistry Adrenoleukodystrophy Long chain fatty acid Oxidation-Reduction Research Article Hepatomegaly |
| Zdroj: | Journal of clinical investigation, 80(6), 1778-1783. The American Society for Clinical Investigation |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci113271 |
| Popis: | The peroxisomal oxidation of the long chain fatty acid palmitate (C16:0) and the very long chain fatty acids lignocerate (C24:0) and cerotate (C26:0) was studied in freshly prepared homogenates of cultured skin fibroblasts from control individuals and patients with peroxisomal disorders. The peroxisomal oxidation of the fatty acids is almost completely dependent on the addition of ATP, coenzyme A (CoA), Mg2+ and NAD+. However, the dependency of the oxidation of palmitate on the concentration of the cofactors differs markedly from that of the oxidation of lignocerate and cerotate. The peroxisomal oxidation of all three fatty acid substrates is markedly deficient in fibroblasts from patients with the Zellweger syndrome, the neonatal form of adrenoleukodystrophy and the infantile form of Refsum disease, in accordance with the deficiency of peroxisomes in these patients. In fibroblasts from patients with X-linked adrenoleukodystrophy the peroxisomal oxidation of lignocerate and cerotate is impaired, but not that of palmitate. Competition experiments indicate that in fibroblasts, as in rat liver, distinct enzyme systems are responsible for the oxidation of palmitate on the one hand and lignocerate and cerotate on the other hand. Fractionation studies indicate that in rat liver activation of cerotate and lignocerate to cerotoyl-CoA and lignoceroyl-CoA, respectively, occurs in two subcellular fractions, the endoplasmic reticulum and the peroxisomes but not in the mitochondria. In homogenates of fibroblasts from patients lacking peroxisomes there is a small (25%) but significant deficiency of the ability to activate very long chain fatty acids. This deficient activity of very long chain fatty acyl-CoA synthetase is also observed in fibroblast homogenates from patients with X-linked adrenoleukodystrophy. We conclude that X-linked adrenoleukodystrophy is caused by a deficiency of peroxisomal very long chain fatty acyl-CoA synthetase. |
| Databáze: | OpenAIRE |
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