Yeast acyl-CoA synthetases at the crossroads of fatty acid metabolism and regulation

Acyl-CoA synthetases (ACSs) are a family of enzymes that catalyze the thioesterification of fatty acids with coenzymeA to form activated intermediates, which play a fundamental role in lipid metabolism and homeostasis of lipid-related processes. The products of the ACS enzyme reaction, acyl-CoAs, are required for complex lipid synthesis, energy production via β-oxidation, protein acylation and fatty-acid dependent transcriptional regulation. ACS enzymes are also necessary for fatty acid import into cells by the process of vectorial acylation. 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. Pivotal roles have been defined for Faa1p and Faa4p in fatty acid import, β-oxidation and transcriptional control mediated by the transcription factors Oaf1p/Pip2p and Mga2p/Spt23p. Fat1p is a bifunctional protein required for fatty acid transport of long chain fatty acids, as well as activation of very long chain fatty acids. This review focuses on the various roles yeast ACS enzymes play in cellular metabolism targeting especially the functions of specific isoforms in fatty acid transport, metabolism and energy production. We will also present evidence from directed experimentation, as well as information obtained by mining the molecular biological databases suggesting the long chain ACS enzymes are required in protein acylation, vesicular trafficking, signal transduction pathways and cell wall synthesis.