Disease relevance of FAT1

• Very long chain acyl-CoA synthetase activity is reduced in strains containing a disrupted FAT1 gene and is increased when FAT1 is expressed in insect cells under control of a baculovirus promoter [1].
• The extent of both the decrease in peroxisomal VLCS activity and the very long-chain fatty acid accumulation in the yeast FAT1 deletion model resembles that observed in cells from X-linked adrenoleukodystrophy patients [2].

High impact information on FAT1

• Murine FATP1, -2, and -4 complemented the defects in fatty acid transport and very long-chain fatty acid activation associated with a deletion of the yeast FAT1 gene; mmFATP3, -5, and -6 did not complement the transport function even though each was localized to the yeast plasma membrane [3].
• To investigate the structural basis of regioselectivity in membrane-bound desaturases, the Caenorhabditis elegans omega-3 (FAT-1) and "Delta12" (FAT-2) desaturases were used as a model system [4].
• The structural basis for nu+3 and omega-3 regioselectivities was examined through construction and expression of chimeric DNA sequences based on FAT-1 and FAT-2 [4].
• Chromosomally encoded FAA1 and FAT1 are not able to suppress the growth deficiencies of the fat1Delta faa1Delta and faa1Delta faa4Delta strains, respectively, indicating Faa1p and Fat1p play distinct roles in the fatty acid import process [5].
• Multicopy FAA4 could not suppress the growth defect in the faa1Delta fat1Delta strain indicating some essential functions of Fat1p cannot be performed by Faa4p [5].

Biological context of FAT1

• Collectively, these data support the hypothesis that fatty acid import by vectorial acylation in yeast requires a multiprotein complex, which consists of Fat1p and Faa1p or Faa4p [5].
• When expressed from a 2-mu plasmid, Fat1p contributes significant oleoyl-CoA synthetase activity, which indicates vectorial esterification and metabolic trapping are the driving forces behind import [5].
• Expression of either Fat1p or murine FATP from a plasmid in a fat1Delta strain restored these phenotypic and biochemical deficiencies [6].
• The yeast Saccharomyces cerevisiae has four long chain ACS enzymes designated Faa1p through Faa4p, one very long chain ACS named Fat1p and one ACS, Fat2p, for which substrate specificity has not been defined [7].

Associations of FAT1 with chemical compounds

• FAT1 deletion strains grown on either dextrose or oleic acid medium accumulated very long-chain fatty acids [2].
• FAT1 deletion strains exhibited decreased growth on medium containing dextrose, oleic acid, and cerulenin, an inhibitor of fatty acid synthesis [2].
• The FAT1 gene encodes a protein, Fat1p, which is required for maximal levels of fatty-acid import and has an acyl CoA synthetase activity specific for very-long-chain fatty acids suggesting this protein plays a pivotal role in fatty-acid trafficking [6].
• In this way, the structural determinants of regioselectivity in FAT-1 and FAT-2 have been localized to two interdependent regions: a relatively hydrophobic region between the first two histidine boxes and the carboxyl-terminal region [4].

Other interactions of FAT1

• PKC1, encoding a protein kinase C, and FAT1, encoding a fatty acid transporter protein, are neighbors in Cochliobolus heterostrophus [8].

References