Adrenoleukodystrophy: Impaired oxidation of fatty acids due to peroxisomal lignoceroyl-CoA ligase deficiency

Lazo, Oscar; Contreras, Miguel Á.; Bhushan, Alok; Stanley, Wayne S.; Singh, Inderjit

doi:10.1016/0003-9861(89)90555-9

Cited by 67 publications

(40 citation statements)

References 30 publications

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“…The livers from control and experimental rats (7 g each) were homogenized in 10 volumes of homogenization buffer (sucrose, 0.25 mol/L; ethylenediaminetetraacetic acid, 1 mmol/L; antipain, 1 mg/mL; aprotinin, 2 mg/mL; leupeptin, 2 mg/mL; pepstatin A, 0.7 mg/mL; phosphoramidon, 0.1 mmol/L; phenylmethylsulfonyl fluoride, 0.2 mmol/L; ethanol, 0.1% (vol/vol); imidazole, 3 mmol/L; pH 7.4) at 4°C. The homogenates were first fractionated by differential centrifugation to prepare the lambda fraction (light mitochondrial fraction enriched with peroxisomes and lysosomes 28 ). The lambda fraction was further subjected to isopycnic equilibrium centrifugation in a continuous (0-50% [wt/ vol]) Nycodenz gradient overlying a cushion of 55% (wt/vol) of Nycodenz as described previously.…”

Section: Preparation Of Rat Liver Subcellular Organelles By Differentmentioning

confidence: 99%

“…The lambda fraction was further subjected to isopycnic equilibrium centrifugation in a continuous (0-50% [wt/ vol]) Nycodenz gradient overlying a cushion of 55% (wt/vol) of Nycodenz as described previously. 28 The gradients were collected in 1.5-mL fractions from the bottom of the tubes. Each fraction was analyzed for marker enzyme activities.…”

Section: Preparation Of Rat Liver Subcellular Organelles By Differentmentioning

confidence: 99%

“…The location of the subcellular organelles in the gradient was determined using specific marker enzymes: catalase for peroxisomes, cytochrome c oxidase for mitochondria, and NADPH cytochrome c reductase for endoplasmic reticulum (ER, microsomes), as described elsewhere. 28 The protein concentrations were determined by the procedure of Bradford, 29 using ␥-globulin as standard of proteins.…”

Section: Preparation Of Rat Liver Subcellular Organelles By Differentmentioning

confidence: 99%

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Endotoxin induces structure-function alterations of rat liver peroxisomes: Kupffer cells released factors as possible modulators

et al. 2000

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We report that endotoxin treatment results in decreased amounts of peroxisomes as well as changes in structure and function of peroxisomal membranes. Peroxisomes isolated from the liver of control and treated animals showed a marked decrease in total protein, but no significant alteration in the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) protein profile. However, the Western blot study of the peroxisomal ␤-oxidation enzymes and catalase showed an increase in those enzymes in the peroxisomal peak of normal density in endotoxin-treated rats.

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Section: Preparation Of Rat Liver Subcellular Organelles By Differentmentioning

confidence: 99%

Section: Preparation Of Rat Liver Subcellular Organelles By Differentmentioning

confidence: 99%

Section: Preparation Of Rat Liver Subcellular Organelles By Differentmentioning

confidence: 99%

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Endotoxin induces structure-function alterations of rat liver peroxisomes: Kupffer cells released factors as possible modulators

et al. 2000

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“…This results in the accumulation of VLCFAs in serum and in various tissues, mainly brain and adrenals (1). The defect was thought to lie in the activation of VLCFAs catalyzed by a VLCFA CoA synthetase, as the latter activity was found decreased in peroxisomes from ALD patients (3,4). VLCFA catabolism is also impaired, together with several other biochemical functions, in Zellweger syndrome, a very severe and genetically heterogeneous disease (with at least nine complementation groups) characterized by abnormal peroxisome biogenesis (2,5).…”

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confidence: 99%

A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal protein with a specific expression pattern.

Lombard-Platet¹,

Savary²,

Sarde³

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

205

133

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Adrenoleukodystrophy (ALD), a severe demyelinating disease, is caused by mutations in a gene coding for a peroxisomal membrane protein (ALDP), which belongs to the superfamily of ATP binding cassette (ABC) transporters and has the structure of a half transporter. ALDP showed 38% sequence identity with another peroxisomal membrane protein, PMP70, up to now its closest homologue. We describe here the cloning and characterization of a mouse ALD-related gene (ALDR), which codes for a protein with 66% identity with ALDP and shares the same half transporter structure. The ALDR protein was overexpressed in COS cells and was found to be associated with the peroxisomes. The ALD and ALDR genes show overlapping but clearly distinct expression patterns in mouse and may thus play similar but nonequivalent roles. The ALDR gene, which appears highly conserved in

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“…The deficient activity of lignoceroyl-CoA ligase as compared to the normal oxidation of lignoceroyl-CoA in purified peroxisomes supported this conclusion [14,17]. These observations suggested that the gene coding for lignoceroylCoA ligase may be a candidate for the X-ALD gene; however, the recent identification of the ALD gene by positional cloning [18][19][20] led to a different conclusion.…”

Section: Introductionmentioning

confidence: 89%

The protein coded by the X‐adrenoleukodystrophy gene is a peroxisomal integral membrane protein

et al. 1994

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The gene for adrenoleukodystrophy (X-ALD), a peroxisomal disease characterized by excessive accumulation of very long-chain (VLC) fatty acids (> C22: 07, has recently been identified by positional cloning, and it is predicted to encode a protein (ALD-P) of 745 amino acids [(1993) Nature 361, 726]. Using Western blot analysis of subcellular organelles purified by isopycnic density gradient centrifugation from X-ALD and control fibroblasts, we show that the monoclonal antibodies directed against ALD-P cross-react with a 75 kDa protein in intact peroxisomes and that ALD-P is an integral component of the peroxisomal membrane. Moreover, no signal for ALD-P was detected in peroxisomes from X-ALD patients with deletion of the ALD gene.

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Adrenoleukodystrophy: Impaired oxidation of fatty acids due to peroxisomal lignoceroyl-CoA ligase deficiency

Cited by 67 publications

References 30 publications

Endotoxin induces structure-function alterations of rat liver peroxisomes: Kupffer cells released factors as possible modulators

Endotoxin induces structure-function alterations of rat liver peroxisomes: Kupffer cells released factors as possible modulators

A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal protein with a specific expression pattern.

The protein coded by the X‐adrenoleukodystrophy gene is a peroxisomal integral membrane protein

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