Mouse very long-chain acyl-CoA synthetase in X-linked adrenoleukodystrophy.

Abstract	X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder characterized by accumulation of very long-chain fatty acids (VLCFA). This accumulation has been attributed to decreased VLCFA beta-oxidation and peroxisomal very long-chain acyl-CoA synthetase (VLCS) activity. The X-ALD gene, ABCD1, encodes a peroxisomal membrane ATP binding cassette transporter, ALDP, that is hypothesized to affect VLCS activity in peroxisomes by direct interaction with the VLCS enzyme. Recently, a VLCS gene that encodes a protein with significant sequence identity to known rat and human peroxisomal VLCS protein has been identified in mice. We find that the mouse VLCS gene (Vlcs) encodes an enzyme (Vlcs) with VLCS activity that localizes to peroxisomes and is expressed in X-ALD target tissues. We show that the expression of Vlcs in the peroxisomes of X-ALD mouse fibroblasts improves VLCFA beta-oxidation in these cells, implying a role for this enzyme in the biochemical abnormality of X-ALD. X-ALD mice, which accumulate VLCFA in tissues, show no change in the expression of Vlcs, the subcellular localization of Vlcs, or general peroxisomal VLCS activity. These observations imply that ALDP is not necessary for the proper expression or localization of Vlcs protein, and the control of VLCFA levels does not depend on the direct interaction of Vlcs and ALDP.
Authors	Ann K Heinzer, Stephan Kemp, Jyh-Feng Lu, Paul A Watkins, Kirby D Smith
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 277 Issue 32 Pg. 28765-73 (Aug 09 2002) ISSN: 0021-9258 [Print] United States
PMID	12048192 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	DNA, Complementary Repressor Proteins Saccharomyces cerevisiae Proteins Catalase Coenzyme A Ligases FAA2 protein, S cerevisiae long-chain-fatty-acid-CoA ligase
Topics	Adrenoleukodystrophy (enzymology, genetics) Amino Acid Sequence Animals Blotting, Northern Blotting, Western COS Cells Catalase (metabolism) Cells, Cultured Cloning, Molecular Coenzyme A Ligases (biosynthesis, genetics) DNA, Complementary (metabolism) Fibroblasts (metabolism) Immunohistochemistry Liver (enzymology) Mice Microscopy, Fluorescence Microsomes, Liver (enzymology) Molecular Sequence Data Peroxisomes (metabolism) Phenotype Protein Binding Repressor Proteins Reverse Transcriptase Polymerase Chain Reaction Saccharomyces cerevisiae Proteins Subcellular Fractions (metabolism) Tissue Distribution Transfection

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