Fatty acids (FA) consisting of up to 16 carbons, are synthesized by the well-studied fatty acid synthase (FAS) complex in the cytosol. However, a significant amount of the fatty acids produced by FAS are further elongated into very long chain fatty acids (VLCFA).
VLCFA have been recognized as structural components in a variety of fat molecules such as sphingolipids, glycerophospholipids, triacylglycerols, sterol- and wax-esters. They are found in virtually all cells and are major constituents of the brain, skin and testis. Depending on their chain length and degree of unsaturation, they contribute to membrane fluidity and other chemical properties of the cell.
The ability to synthesize very-long-chain-fatty-acids (VLCFA) is a ubiquitous system found in all cell types. We have recently identified a novel mammalian gene family, termed the Elovl (Elongation of very long chain fatty acids), which are controlling the synthesis of VLCFA. Interestingly, all the Elovl genes show a distinct tissue specific expression, which indicate that the ELOVL proteins are cell specific regulators of VLCFA formation. To generalize, the fatty acid elongases can be divided into two major groups: a) enzymes which are suggested to be involved in the synthesis of saturated and monounsaturated VLCFA (ELOVL1, 3 and 6) and b) enzymes which are elongases of polyunsaturated fatty acids (PUFA) (ELOVL2, 4 and 5).
Our prospect is a) to identify and explain, both genetically and enzymatically, the regulation of VLCFA synthesis in mammalian cells, b) to identify the target molecules for these VLCFA and c) identify the cellular and physiological significance of these lipid molecules.