Role of acyl-CoA synthetase ACSL4 in arachidonic acid metabolism.

The activation of long-chain free fatty acids is the first step reaction of their usage in the cells and tissues, which are catalyzed by a family of enzymes called acyl-coenzyme A synthetases long-chain isoform (ACSL). The five ACSL enzymes identified in mammals are thought to have specific and differing functions. Among them, ACSL4 is a unique isozyme that preferentially catalyzes several polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA), and ACSL4 is thought to be an important isozyme for PUFA metabolism. Recent studies revealed that ACSL4 is involved in biological responses including inflammation, steroidogenesis, cell death, female fertility, and cancer. ACSL4 and its substrate PUFAs are thus likely to contribute to these responses. However, the roles of ACSL4 in PUFA metabolism are not fully understood. In this review, we describe the recent progress in ACSL4 research including the involvement of this enzyme in AA metabolism.