Clinical variation in X-linked adrenoleukodystrophy: Fatty acid and lipid metabolism in cultured fibroblasts

Debra J. Boles, Debra A. Craft, David A. Padgett, Roger M. Loria, William B. Rizzo

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Abstract

To determine whether the clinical phenotype of ALD correlates with the extent of metabolic abnormality, we investigated VLFA metabolism in cultured fibroblasts from patients with the clinically severe childhood form of ALD and the milder AMN variant. No differences were seen in the content of neutral lipids or phospholipids, in incorporation of [1-14C]lignocerate into cellular lipids, or in the fatty acid composition of fibroblasts from patients with childhood ALD or AMN. [1-14C]Lignocerate oxidation was deficient to a similar extent (35-40% of normal) in both intact fibroblasts and cell homogenates from patients with childhood ALD and AMN. With the use of fibroblast homogenates, oxidation of lignocerate was partially inhibited by various long-chain fatty acids, and residual activity in ALD homogenates was more susceptible to inhibition by palmitate than normal. In the presence of competing palmitate, residual lignocerate oxidative activity in fibroblast homogenates was reduced to 20 ± 4% of normal in childhood ALD and 24 ± 2% of normal in AMN. These results indicate that residual VLFA oxidative activity, fatty acid composition, VLFA metabolism, and lipid content of cultured fibroblasts do not correlate with the clinical expression of the ALD gene.

Original languageEnglish (US)
Pages (from-to)74-91
Number of pages18
JournalBiochemical Medicine and Metabolic Biology
Volume45
Issue number1
DOIs
StatePublished - Feb 1991

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry

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