Vectorial Acylation: Linking Fatty Acid Transport and Activation to Metabolic Trafficking

The process of fatty acid transport across the plasma membrane occurs by several mechanisms that involve distinct membrane-bound and membrane-associated proteins and enzymes. Amongst these are the fatty acid transport proteins (FATP) and long-chain acyl CoA synthetases (ACSL). We have shown the yeast orthologues of FATP and ACSL form a physical complex at the plasma membrane and are required for fatty acid transport, which proceeds through a coupled process linking transport with metabolic activation and termed vectorial acylation. At present six isoforms of FATP and five isoforms of ACSL have been identified in mice and human. In addition there are a number of splice variants of different ACSL isoforms; recent work from our laboratory has found at least one splice variant in human FATP2. The different FATP and ACSL isoforms have distinct tissue expression profiles and along with different cellular locations suggest they function in the trafficking of fatty acids into discrete metabolic pools. More specifically, we hypothesize the different FATP and ACLS isoforms function individually and co-ordinately to move distinct classes of fatty acids into these different metabolic pools. The concerted activity of these proteins allows the cell to discriminate different classes of fatty acids and provides the mechanistic basis underpinning the selectivity and specificity of the fatty acid transport process.