Disease relevance of SLC27A2

• Decreased peroxisomal VLCS activity is, in part, responsible for the biochemical pathology in X-linked adrenoleukodystrophy (X-ALD), illustrating the importance of VLCSs in cellular fatty acid homeostasis [1].

High impact information on SLC27A2

• Furthermore, hVLCS was topographically oriented facing the peroxisomal matrix in both control and X-ALD fibroblasts, contradicting the alternative hypothesis that ALDP is required to translocate VLCS into peroxisomes [2].
• However, overexpression of both hVLCS and ALDP in X-ALD fibroblasts synergistically increased very-long-chain fatty acid beta-oxidation, indicating that these proteins interact functionally [2].
• We reported previously that homolog 2 of very long-chain acyl-CoA synthetase (VLCS) can activate cholate (Steinberg, S. J., Mihalik, S. J., Kim, D. G., Cuebas, D. A., and Watkins, P. A. (2000) J. Biol. Chem. 275, 15605-15608) [3].
• The most recently identified family is the very long-chain acyl-CoA synthetases (VLCS) [4].
• Furthermore, activation of PPARgamma and RXR enhanced the expression of the fat droplet-associated protein adipophilin along with fatty acid transport protein (FATP)4, whereas expression of FATP2 was decreased by activation of RXR [5].

Biological context of SLC27A2

• The amino acid sequence of hVLCS-H2 is 44-45% identical and 67-69% similar to those of both hVLCS and hVLCS-H1 [1].
• Assignment of human fatty-acid-coenzyme A ligase, very long-chain 1 gene (FACVL1) to human chromosome band 15q21.2 by fluorescence in situ hybridization [6].

Anatomical context of SLC27A2

• In peroxisomes of HepG2 cells, hVLCS was topographically oriented facing the matrix and not the cytoplasm [7].
• Immunofluorescence and immunoblot studies localized hVLCS to both peroxisomes and endoplasmic reticulum [7].
• When expressed in COS-1 cells, hVLCS activated the VLCFA lignoceric acid (C24:0), a long-chain fatty acid (C16:0), and two branched-chain fatty acids, phytanic acid and pristanic acid [7].
• Separation of the latter organelles by density gradient centrifugation revealed that VLCS activity was peroxisomal and not mitochondrial [8].
• In FAT1-disruption strains, VLCS activity was reduced to 30-40% of wild-type in both a microsome-rich 27,000 g supernatant fraction and a peroxisome- and mitochondria-rich pellet fraction of yeast spheroplast homogenates [8].

Associations of SLC27A2 with chemical compounds

• While one motif is also present in long-chain acyl-CoA synthetases, the other serves to distinguish the VLCS/FATP family from the long-chain synthetase family [9].
• Very-long-chain acyl-CoA synthetases (VLCS) activate very-long-chain fatty acids (VLCFA) containing 22 or more carbons to their CoA derivatives [7].
• An additional finding was that acitretin (15-30 microM) activated significantly human liver microsomal long-chain fatty acid-CoA ligase (E.C.6.2.1.3, LCL), resulting in enhanced formation of palmitoyl-CoA [10].

Other interactions of SLC27A2

• Studies using a yeast two hybrid system and surface plasmon resonance techniques indicate that ALDP, a peroxisomal membrane protein, physically interacts with VLCS [11].

References