Disease relevance of Slc27a2

• Very long-chain fatty acids, which accumulate in tissues of patients with X-linked adrenoleukodystrophy, are activated by very long-chain acyl-CoA synthetase (VLCS) normally found in peroxisomes and microsomes [1].

High impact information on Slc27a2

• Separation of organelles in the pellet fraction by density gradient centrifugation revealed that VLCS activity was associated with peroxisomes and microsomes but not mitochondria [1].
• These studies suggest that the FAT1 gene product has VLCS activity that is essential for normal cellular very long-chain fatty acid homeostasis [1].
• The level of VLCS activity measured in both wild-type and deletion yeast strains transformed with FAT1 cDNA paralleled the level of expression of the transgene [1].
• The entire structure of VLACS was dissimilar to that of long-chain acyl-CoA synthetase (Suzuki, H., Kawarabayashi, Y., Kondo, Y., Abe, T., Nishikawa, K., Kimura, S., Hashimoto, T., and Yamamoto, T. (1990) J. Biol. Chem. 265, 8681-8685), except for the domains [2].
• The predicted amino acid sequence of VLACS had a high sequence similarity to fatty acid transport protein (Schaffer, J. E., and Lodish, H. F. (1994) Cell 79, 427-436), and was considered to have domains for adenylation and thioester formation [2].

Anatomical context of Slc27a2

• The subcellular localization of VLACS in peroxisomes and microsomes was demonstrated in Western blot analysis [2].
• This suggests that both cell lines are defective in two enzyme activities involved in the pathway, the microsomal THCA-CoA ligase and the peroxisomal THCA-CoA oxidase [3].

Associations of Slc27a2 with chemical compounds

• Furthermore, we show that the subsequent enzymes are active in the conversion to bile acids, because the product of the THCA-CoA oxidase, 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-24-enoyl-coenzyme A (delta 24-THCA-CoA) or delta 24-THCA in the presence of THCA-CoA ligase, are converted to cholic acid by both cell lines [3].
• These data suggest that nafenopin-CoA formation is catalysed by a peroxisomal CoA ligase which differs from the peroxisomal long chain fatty acid-CoA ligase in relation to its xenobiotic/antibody inhibitor profile and kinetic characteristics [4].

References