Very-Long-Chain Fatty Acid Metabolism in Adrenoleukodystrophy Protein-Deficient Mice

Takeshi Yamada, Nobue Shinnoh, Akira Kondo, Atsushi Uchiyama, Nobuyuki Shimozawa, Jun-Ichi Kira, Takuro Kobayashi

Research output: Contribution to journalArticle

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Abstract

X-linked adrenoleukodystrophy (X-ALD) is characterized by progressive mental and motor deterioration, with demyelination of the central and peripheral nervous system. Its principal biochemical abnormality is the accumulation of very-long-chain fatty acids (VLCFAs) in tissues and body fluids, caused by the impairment of peroxisomal β-oxidation. The authors have generated a line of mice deficient in ALD protein (ALDP) by gene targeting. ALDP-deficient mice appeared normal clinically, at least up to 12 mo. Western blot analysis showed absence of ALDP in the brain, spinal cord, lung, and kidney. The amounts of C26:0 increased by 240% in the spinal cord. VLCFA β-oxidation in cultured hepatocytes was reduced to 50% of normal. The authors investigated the roles of ALDP in VLCFA β-oxidation using the ALDP-deficient mice. Very-long-chain acyl-CoA synthetase (VLACS) is functionally deficient in ALD cells. The impairment of VLCFA β-oxidation in the ALDP-deficient fibroblasts was not corrected by over-expression of VLACS only, but was done by co-expression of VLACS and ALDP, suggesting that VLACS requires ALDP to function. VLACS was detected in the peroxisomal and microsomal fractions of the liver from both types of mice. Peroxisomal VLACS was clearly decreased in the ALDP-deficient mouse. Thus, ALDP is involved in the peroxisomal localization of VLACS.

Original languageEnglish
Pages (from-to)239-246
Number of pages8
JournalCell Biochemistry and Biophysics
Volume32
DOIs
Publication statusPublished - Jan 1 2000

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Adrenoleukodystrophy
Metabolism
Fatty Acids
Proteins
Oxidation
Spinal Cord
Gene Targeting
Peripheral Nervous System
Body Fluids
Demyelinating Diseases
Protein Transport
long-chain-fatty-acid-CoA ligase
Body fluids
Neurology
Fibroblasts
Hepatocytes
Liver
Deterioration
Central Nervous System
Western Blotting

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Very-Long-Chain Fatty Acid Metabolism in Adrenoleukodystrophy Protein-Deficient Mice. / Yamada, Takeshi; Shinnoh, Nobue; Kondo, Akira; Uchiyama, Atsushi; Shimozawa, Nobuyuki; Kira, Jun-Ichi; Kobayashi, Takuro.

In: Cell Biochemistry and Biophysics, Vol. 32, 01.01.2000, p. 239-246.

Research output: Contribution to journalArticle

Yamada, Takeshi ; Shinnoh, Nobue ; Kondo, Akira ; Uchiyama, Atsushi ; Shimozawa, Nobuyuki ; Kira, Jun-Ichi ; Kobayashi, Takuro. / Very-Long-Chain Fatty Acid Metabolism in Adrenoleukodystrophy Protein-Deficient Mice. In: Cell Biochemistry and Biophysics. 2000 ; Vol. 32. pp. 239-246.
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