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

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.

• 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.)
• 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

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)