SUMMARY PARAGRAPH for FAT1
In order for yeast to utilize fatty acids, either as an energy source (via beta-oxidation) or for essential processes such as phospholipid biosynthesis and protein myristoylation, the fatty acids must first be converted into activated intermediates, acyl-CoAs, through thioesterification of fatty acids with coenzyme A. When fatty acids are synthesized de novo, activation is part of the process of synthesis and is accomplished by the same fatty acid synthetase complex (Fas1p-Fas2p) that initiates and elongates the fatty acid chain. However, yeast cells can also utilize exogenous, imported fatty acids, an ability that becomes essential if the fatty acid synthetase complex is inactivated by mutation or specific inhibitors such as cerulenin. These exogenous fatty acids are activated by one of five characterized yeast acyl-CoA synthetases: Faa1p, Faa2p, Faa3p, Faa4p, or Fat1p (see 6 and 7 for review).
FAT1 encodes an acyl-CoA synthetase required for both the import of long chain fatty acids (C14-C18) and the activation very long chain fatty acids (C20-C26) (2, 1, 8, 4). Disruption of FAT1 results in a decrease in the uptake of fatty acids, as measured by the import of fluorescently labeled long-chain fatty acid analogues and [3H]oleate (2, 3). fat1 deletion mutants also accumulate very long chain fatty acids (e.g. lignoceric acid (C24:0)) and exhibit decreased activation of these fatty acids (1, 8). Examination of a series of fat1 mutant alleles showed that these transport and fatty acyl-CoA synthetase defects are genetically separable and are thus independent activities (4).
faa1faa4 double deletion mutants also have severe defects in the import of long chain fatty acids, indicating that these genes play some role in transport as well (8, 5). Overexpression of FAT1 can rescue the faa1faa4 import phenotype and there is evidence of physical interaction between Fat1p and Faa1p and/or Faa4p (5). Fat1p, Faa1p and Faa4p are hypothesized to couple import and activation of exogenous fatty acids by a process called vectorial acylation, wherein fatty acids are metabolically trapped as CoA thioesters upon transport (reviewed in 7). This process is thought to require Fat1p along with either Faa1p and/or Faa4p (5).
The FAT1 gene was originally identified by similarity to murine Fatty Acid Transport Protein 1 (FATP1) (2, <9660783>8) and FATP1 expressed in S. cerevisiae can rescue fat1 phenotypes (3).9660783>
Last updated: 2010-02-11