Peroxisomal acyl-CoA synthetases

Abstract

Peroxisomes carry out many essential lipid metabolic functions. Nearly all of these functions require that an acyl group – either a fatty acid or the acyl side chain of a steroid derivative – be thioesterified to coenzyme A (CoA) for subsequent reactions to proceed. This thioesterification, or “activation”, reaction, catalyzed by enzymes belonging to the acyl-CoA synthetase (ACS) family, is thus central to cellular lipid metabolism. However, despite our rather thorough understanding of peroxisomal metabolic pathways, surprisingly little is known about the specific peroxisomal ACSs that participate in these pathways. Of the 26 ACSs encoded by the human and mouse genomes, only a few have been reported to be peroxisomal, including ACSL4, ACSVL1 (FATP2), and FATP4. In this review, we briefly describe the primary peroxisomal lipid metabolic pathways in which fatty acyl-CoAs participate. Then, we examine the evidence for presence and functions of ACSs in peroxisomes, much of which was obtained before the existence of multiple ACS isoenzymes was known. Finally, we discuss the role(s) of peroxisome-specific ACS isoforms in lipid metabolism.

Latent luciferase activity in the fruit fly revealed by a synthetic luciferin

“…The selectivity of CG6178 for CycLuc2 over D-luciferin could potentially be exploited for the design of new substrateselective luciferases (10), perhaps by combining features of both beetle luciferases and ACSLs. Furthermore, although we did not observe bioluminescence from the mammalian ACSLs in CHO cells, which have lower homology to firefly luciferase, mammalian ACS enzymes are known to adenylate xenobiotics such as ibuprofen (32,33). We therefore expect that probing the intersection between the luminogenic chemistry of small-molecule luciferin analogs (16,(34)(35)(36)(37)(38)(39)(40) and the activation chemistry of existing adenylating enzymes (33) will reveal that latent luciferase activity is more common than previously thought.…”

Identification of acyl-CoA synthetases involved in the mammalian sphingosine 1-phosphate metabolic pathway

“…Therefore, ACSs responsible for S1P metabolism should also be localized in the ER for efficient metabolic flow. It has been reported that each ACS isozyme exhibits characteristic intracellular localization, such as in the ER, plasma membrane, mitochondria, and peroxisome [7,13,14]. However, the precise localization of most ACS isozymes remains unclear since inconsistent localization patterns have been reported among researchers using different approaches.…”

Gene Expression Profile and Signaling Pathways in MCF-7 Breast Cancer Cells Mediated by Acyl-Coa Synthetase 4 Overexpression

“…ACSL4 belongs to a five-member family of enzymes that esterifies mainly arachidonic acid (AA) into acyl-CoA [2][3][4][5]. Unlike the other ACSL isoforms, ACSL4 is encoded on the X chromosome and its expression is highest in adrenal cortex, ovary and testis [6][7][8][9][10], as well as in mouse and human cerebellum and hippocampus [11]. Studies on the physiological functions of ACSL4 have revealed possible roles in polyunsaturated fatty acid metabolism in brain, in steroidogenesis, in eicosanoid metabolism related to apoptosis and embryogenesis [8][9][10][11][12][13][14].…”

“…Unlike the other ACSL isoforms, ACSL4 is encoded on the X chromosome and its expression is highest in adrenal cortex, ovary and testis [6][7][8][9][10], as well as in mouse and human cerebellum and hippocampus [11]. Studies on the physiological functions of ACSL4 have revealed possible roles in polyunsaturated fatty acid metabolism in brain, in steroidogenesis, in eicosanoid metabolism related to apoptosis and embryogenesis [8][9][10][11][12][13][14]. ACSL4 expression has also been associated with non-physiological functions such as mental retardation disorder [15,16] and cancer [2,3,17,18].…”