Abstract |
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.
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Authors | L T Braiterman, P A Watkins, A B Moser, K D Smith |
Journal | Molecular genetics and metabolism
(Mol Genet Metab)
Vol. 66
Issue 2
Pg. 91-9
(Feb 1999)
ISSN: 1096-7192 [Print] United States |
PMID | 10068511
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Copyright | Copyright 1999 Academic Press. |
Chemical References |
- ABCD1 protein, human
- ATP Binding Cassette Transporter, Subfamily D, Member 1
- ATP-Binding Cassette Transporters
- Fatty Acids, Nonesterified
- Membrane Proteins
- Phytanic Acid
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Topics |
- ATP Binding Cassette Transporter, Subfamily D, Member 1
- ATP-Binding Cassette Transporters
(genetics, metabolism)
- Adrenoleukodystrophy
(genetics)
- Cell Line
- Cell Line, Transformed
- Fatty Acids, Nonesterified
(metabolism)
- Fibroblasts
(metabolism)
- Humans
- Membrane Proteins
(genetics, metabolism)
- Microbodies
(metabolism)
- Oxidation-Reduction
- Phytanic Acid
(metabolism)
- Reference Values
- Simian virus 40
- Skin
(metabolism)
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