Disease relevance of Slc27a2

• X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder with impaired beta-oxidation of very long chain fatty acids (VLCFAs) and reduced function of peroxisomal very long chain fatty acyl-CoA synthetase (VLCS) that leads to severe and progressive neurological disability [1].
• Skin fibroblast mRNA levels for ACSVL1, an enzyme previously shown to be in peroxisomes and to participate in VLCFA beta-oxidation, were not significantly different between normal controls, patients with childhood cerebral X-ALD, and patients with adrenomyeloneuropathy [2].

High impact information on Slc27a2

• The XALD/Vlcs double knockout mouse has the biochemical abnormalities observed in the individual knockout mice but does not display a more severe X-ALD phenotype [3].
• The family of proteins that includes very long-chain acyl-CoA synthetases (ACSVL) consists of six members [4].
• 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 [5].
• In ALD, very long-chain acyl-coenzyme A synthetase (VLACS), which is necessary for peroxisomal beta-oxidation, does not function [6].
• CONCLUSIONS: ALDP plays a role in the peroxisomal localization of VLACS, and VLACS does not function unless localized in the peroxisome [6].

Anatomical context of Slc27a2

• By RT-PCR VLACS mRNA was also detected in heart and lung but remained undetectable in skeletal muscle and spleen [7].

Other interactions of Slc27a2

• As a first step to studying this interaction in wild type versus ALDP-deficient mice, we have cloned a VLACS cDNA from mouse liver [7].
• In contrast to the peroxisomal beta-oxidation marker acyl-CoA oxidase, whose mRNA level steadily increases during brain development, the VLACS transcript was found at a constant low level from embryo through adulthood, suggesting that additional isoforms may exist in brain [7].
• We conclude that the role, if any, of ACSVL1 and BG1 in X-ALD biochemical pathology is indirect [2].

Analytical, diagnostic and therapeutic context of Slc27a2

• By Northern blot analysis, a 2.6-kb VLACS mRNA was highly abundant only in mouse liver [8].
• The peroxisomal localization of VLACS was compared between the mutant and control mice using a Western blot analysis [6].

References