Peroxisomal very long chain fatty acid beta-oxidation activity is determined by the level of adrenodeukodystrophy protein (ALDP) expression

Mol Genet Metab. 1999 Feb;66(2):91-9. doi: 10.1006/mgme.1998.2789.


Impaired peroxisomal beta-oxidation of saturated very long chain fatty acids (VLCFA, >/=C22:0) results in increased VLCFA levels in the tissues and body fluids of patients with disorders of peroxisomal biogenesis (i.e., Zellweger syndrome and neonatal adrenoleukodystrophy) and single peroxisomal protein defects (i.e., X-linked adrenoleukodystrophy (X-ALD) and acyl-CoA oxidase deficiency). We show that SV40T transformation also results in impaired peroxisomal beta-oxidation and VLCFA accumulation despite the presence of abundant peroxisomes. To explore the mechanism responsible for this observation, we have examined expression of key components of peroxisomal VLCFA beta-oxidation. We found that expression of both acyl-CoA oxidase, the rate limiting enzyme of peroxisomal VLCFA beta-oxidation and the adrenoleukodystrophy protein (ALDP), the defective gene product in X-ALD, are reduced after SV40T transformation. Surprisingly, ALDP overexpression by itself restores peroxisomal VLCFA beta-oxidation in SV40T-transformed control and X-ALD cells. These results demonstrate that ALDP is a fundamental component in VLCFA peroxisomal beta-oxidation and may serve as a "gatekeeper" for VLCFA homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism*
  • Adrenoleukodystrophy / genetics*
  • Cell Line
  • Cell Line, Transformed
  • Fatty Acids, Nonesterified / metabolism*
  • Fibroblasts / metabolism
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Microbodies / metabolism*
  • Oxidation-Reduction
  • Phytanic Acid / metabolism
  • Reference Values
  • Simian virus 40
  • Skin / metabolism


  • ABCD1 protein, human
  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters
  • Fatty Acids, Nonesterified
  • Membrane Proteins
  • Phytanic Acid