Peroxisomal lignoceroyl-CoA ligase deficiency in childhood adrenoleukodystrophy and adrenomyeloneuropathy

Journal Article · Sat Oct 01 00:00:00 EDT 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.20.7647· OSTI ID:5606559

Lazo, O; Contreras, M; Hashmi, M; Stanley, W; Irazu, C; Singh, I ^[1]

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1. Medical Univ. of South Carolina, Charleston (USA)

The authors previously reported that in childhood adrenoleukodystrophy (C-ALD) and adrenomyeloneuropathy (AMN), the peroxisomal {beta}-oxidation system for very long chain fatty acids is defective. To further define the defect in these two forms of X chromosome-linked ALD, they examined the oxidation of (1-{sup 14}C)lignoceric acid (n-tetracosanoic acid, C24:0) and (1-{sup 14}C)lignoceroyl-CoA (substrates for the first and second steps of {beta}-oxidation, respectively). The oxidation rates of lignoceric acid in C-ALD and AMN were 43% and 36% of control values, respectively, whereas the oxidation rate of lignoceroyl-CoA was 109% (C-ALD) and 106% (AMN) of control values, respectively. These results suggest that lignoceroyl-CoA ligase activity may be impaired in C-ALD and AMN. To identify the specific enzymatic deficiency and its subcellular localization in C-ALD and AMN, they established a modified procedure for the subcellular fractionation of cultured skin fibroblasts. Determination of acyl-CoA ligase activities provided direct evidence that lignoceroyl-CoA ligase is deficient in peroxisomes while it is normal in mitochondria and microsomes. These data clearly demonstrate that the pathognomonic accumulation of very long chain fatty acids in C-ALD and AMN is due to a deficiency of peroxisomal very long chain (lignoceric acid) acyl-CoA ligase.

• OSTI ID: 5606559
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 85:20; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CARBON 14 COMPOUNDS
OXIDATION
CARBOXYLIC ACIDS
HEREDITARY DISEASES
BIOCHEMISTRY
LIGASES
ENZYME ACTIVITY
CHILDREN
FIBROBLASTS
SKIN
X CHROMOSOME
AGE GROUPS
ANIMAL CELLS
BODY
CHEMICAL REACTIONS
CHEMISTRY
CHROMOSOMES
CONNECTIVE TISSUE CELLS
DISEASES
ENZYMES
HETEROCHROMOSOMES
LABELLED COMPOUNDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
SOMATIC CELLS
550401* - Genetics- Tracer Techniques