ACSL1 explained

Long-chain-fatty-acid—CoA ligase 1 is an enzyme that in humans is encoded by the ACSL1 gene.^{[1] [2] [3]}

Structure

Gene

The ACSL1 gene is located on the 4th chromosome, with its specific location being 4q35.1. The gene contains 28 exons. In melanocytic cells ACSL1 gene expression may be regulated by MITF.^[4]

Function

The protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family. Although differing in substrate specificity, subcellular localization, and tissue distribution, all isozymes of this family convert free long-chain fatty acids into fatty acyl-CoA esters, and thereby play a key role in lipid biosynthesis and fatty acid degradation. Several transcript variants encoding different isoforms have been found for this gene. This specific protein is most commonly found in mitochondria and peroxisomes.^[5]

Clinical significance

ACSL1 is known to be involved in fatty-acid metabolism critical for heart function and nonspecific mental retardation.^[6] Since the ACSL4 gene is highly expressed in brain, where it encodes a brain specific isoform, an ASCL1 mutation may be an efficient diagnostic tool in mentally retarded males.^[7]

Interactions

ACSL1 expression is regulated by SHP2 activity.^[8] Additionally, ACSL1 interacts with ACSL3, APP, DSE, ELAVL1, HECW2, MINOS1, PARK2, SPG20, SUMO2, TP53, TUBGCP3, UBC, UBD, and YWHAQ.^[3]

Further reading

• Amigo L, McElroy MC, Morales MN, Bronfman M . Subcellular distribution and characteristics of ciprofibroyl-CoA synthetase in rat liver. Its possible identity with long-chain acyl-CoA synthetase . The Biochemical Journal . 284 . 1 . 283–7 . May 1992 . 1599407 . 1132728 . 10.1042/bj2840283.
• Abe T, Fujino T, Fukuyama R, Minoshima S, Shimizu N, Toh H, Suzuki H, Yamamoto T . Human long-chain acyl-CoA synthetase: structure and chromosomal location . Journal of Biochemistry . 111 . 1 . 123–8 . Jan 1992 . 1607358 . 10.1093/oxfordjournals.jbchem.a123707.
• Lageweg W, Wanders RJ, Tager JM . Long-chain-acyl-CoA synthetase and very-long-chain-acyl-CoA synthetase activities in peroxisomes and microsomes from rat liver. An enzymological study . European Journal of Biochemistry . 196 . 2 . 519–23 . Mar 1991 . 2007410 . 10.1111/j.1432-1033.1991.tb15844.x . free .
• Singh I, Bhushan A, Relan NK, Hashimoto T . Acyl-CoA ligases from rat brain microsomes: an immunochemical study . Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism . 963 . 3 . 509–14 . Dec 1988 . 2973813 . 10.1016/0005-2760(88)90319-0 .
• Bierbach H . Studies on long chain fatty acid:CoA ligase from human small intestine . Gut . 21 . 8 . 689–94 . Aug 1980 . 7429333 . 1419104 . 10.1136/gut.21.8.689 .
• Cantú ES, Sprinkle TJ, Ghosh B, Singh I . The human palmitoyl-CoA ligase (FACL2) gene maps to the chromosome 4q34-q35 region by fluorescence in situ hybridization (FISH) and somatic cell hybrid panels . Genomics . 28 . 3 . 600–2 . Aug 1995 . 7490105 . 10.1006/geno.1995.1199 .
• Wu P, Bremer J . Activation of alkylthioacrylic acids in subcellular fractions of rat tissues: a new spectrophotometric method for assay of acyl-CoA synthetase . Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism . 1215 . 1–2 . 87–92 . Nov 1994 . 7948012 . 10.1016/0005-2760(94)90095-7 .
• Singh I, Lazo O, Kremser K . Purification of peroxisomes and subcellular distribution of enzyme activities for activation and oxidation of very-long-chain fatty acids in rat brain . Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism . 1170 . 1 . 44–52 . Sep 1993 . 8399326 . 10.1016/0005-2760(93)90174-8 .
• Ghosh B, Barbosa E, Singh I . Molecular cloning and sequencing of human palmitoyl-CoA ligase and its tissue specific expression . Molecular and Cellular Biochemistry . 151 . 1 . 77–81 . Oct 1995 . 8584017 . 10.1007/BF01076899 . 7476738 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . Sep 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Malhotra KT, Malhotra K, Lubin BH, Kuypers FA . Identification and molecular characterization of acyl-CoA synthetase in human erythrocytes and erythroid precursors . The Biochemical Journal . 344 . 1 . 135–43 . Nov 1999 . 10548543 . 1220623 . 10.1042/0264-6021:3440135 .
• Mashek DG, Bornfeldt KE, Coleman RA, Berger J, Bernlohr DA, Black P, DiRusso CC, Farber SA, Guo W, Hashimoto N, Khodiyar V, Kuypers FA, Maltais LJ, Nebert DW, Renieri A, Schaffer JE, Stahl A, Watkins PA, Vasiliou V, Yamamoto TT . Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family . Journal of Lipid Research . 45 . 10 . 1958–61 . Oct 2004 . 15292367 . 10.1194/jlr.E400002-JLR200 . free .
• Soupene E, Kuypers FA . Multiple erythroid isoforms of human long-chain acyl-CoA synthetases are produced by switch of the fatty acid gate domains . BMC Molecular Biology . 7 . 21 . 2006 . 16834775 . 1543647 . 10.1186/1471-2199-7-21 . free .

Notes and References

1. Suzuki H, Kawarabayasi Y, Kondo J, Abe T, Nishikawa K, Kimura S, Hashimoto T, Yamamoto T . Structure and regulation of rat long-chain acyl-CoA synthetase . The Journal of Biological Chemistry . 265 . 15 . 8681–5 . May 1990 . 10.1016/S0021-9258(19)38942-2 . 2341402 . free .
2. Stanczak H, Stanczak JJ, Singh I . Chromosomal localization of the human gene for palmitoyl-CoA ligase (FACL1) . Cytogenetics and Cell Genetics . 59 . 1 . 17–9 . Feb 1992 . 1531127 . 10.1159/000133189 .
3. Web site: Entrez Gene: ACSL1 acyl-CoA synthetase long-chain family member 1.
4. Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E . Novel MITF targets identified using a two-step DNA microarray strategy . Pigment Cell & Melanoma Research . 21 . 6 . 665–76 . Dec 2008 . 19067971 . 10.1111/j.1755-148X.2008.00505.x . 24698373 . free .
5. Singh I, Lazo O, Kremser K . Purification of peroxisomes and subcellular distribution of enzyme activities for activation and oxidation of very-long-chain fatty acids in rat brain . Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism . 1170 . 1 . 44–52 . Sep 1993 . 8399326 . 10.1016/0005-2760(93)90174-8.
6. Meloni I, Muscettola M, Raynaud M, Longo I, Bruttini M, Moizard MP, Gomot M, Chelly J, des Portes V, Fryns JP, Ropers HH, Magi B, Bellan C, Volpi N, Yntema HG, Lewis SE, Schaffer JE, Renieri A . FACL4, encoding fatty acid-CoA ligase 4, is mutated in nonspecific X-linked mental retardation . Nature Genetics . 30 . 4 . 436–40 . Apr 2002 . 11889465 . 10.1038/ng857 . 23901437 .
7. Longo I, Frints SG, Fryns JP, Meloni I, Pescucci C, Ariani F, Borghgraef M, Raynaud M, Marynen P, Schwartz C, Renieri A, Froyen G . A third MRX family (MRX68) is the result of mutation in the long chain fatty acid-CoA ligase 4 (FACL4) gene: proposal of a rapid enzymatic assay for screening mentally retarded patients . Journal of Medical Genetics . 40 . 1 . 11–7 . Jan 2003 . 12525535 . 10.1136/jmg.40.1.11 . 1735250.
8. Cooke M, Orlando U, Maloberti P, Podestá EJ, Cornejo Maciel F . Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4 . Journal of Lipid Research . 52 . 11 . 1936–48 . Nov 2011 . 21903867 . 10.1194/jlr.m015552 . free . 3196225.