Structure and regulation of rat long-chain acyl-CoA synthetase.

Suzuki, Hiroyuki; Kawarabayasi, Yutaka; Kondo, Jun; Abé, Tatsuya; Nishikawa, Kazuhiro; Kimura, Seiji; Hashimoto, Takafumi; Yamamoto, Tokuo

doi:10.1016/s0021-9258(19)38942-2

Cited by 331 publications

(38 citation statements)

References 24 publications

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“…Acyl-CoAs originate from circulating fatty acids that are taken up by cells via fatty acid translocases such as FAT/CD36, very-long chain fatty acyl-CoA synthetases, and caveolin-1. 22 Acyl-CoAs, which are generated via acyl-CoA synthetases (ACS) 23 24 25 ( Fig. 1 ), are used for energy production via β-oxidation 26 and as substrates for the synthesis of various complex lipids including triacylglycerols, phospholipids, cholesterol esters and SLs.…”

Section: The Acyl Chain Complexity Of Slsmentioning

confidence: 99%

The Complex Tail of Circulating Sphingolipids in Atherosclerosis and Cardiovascular Disease

Zelnik

Kim

Futerman

2021

J Lipid Atheroscler

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Sphingolipids (SLs) are critical players in a number of cellular processes and have recently been implicated in a large number of human diseases, including atherosclerosis and cardiovascular disease (CVD). SLs are generated intracellularly in a stepwise manner, starting with the generation of the sphingoid long chain base (LCB), followed by N -acylation of the LCB to form ceramide, which can be subsequently metabolized to sphingomyelin and glycosphingolipids. Fatty acids, which are taken up by cells prior to their activation to fatty acyl-CoAs, are used in 2 of these enzymatic steps, including by ceramide synthases, which use fatty acyl-CoAs of different chain lengths to generate ceramides with different N -acyl chain lengths. Recently, alterations in plasma ceramides with specific N -acyl chain lengths and degrees of saturation have emerged as novel biomarkers for the prediction of atherosclerosis and overall cardiovascular risk in the general population. We briefly review the sources of plasma SLs in atherosclerosis, the roles of SLs in CVD, and the possible use of the “ceramide score” as a prognostic marker for CVD.

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Section: The Acyl Chain Complexity Of Slsmentioning

confidence: 99%

The Complex Tail of Circulating Sphingolipids in Atherosclerosis and Cardiovascular Disease

Zelnik

Kim

Futerman

2021

J Lipid Atheroscler

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“…The first mammalian long-chain acyl-CoA synthetase was isolated from rat liver in 1990, currently annotated as ACSL1 (41). The first form isolated from brain tissue was ACSL6 but was mistakenly identified as a PI 4-kinase (phosphatidylinositol 4-kinase) (42).…”

Section: Localization Of the Acsl Formsmentioning

confidence: 99%

Mammalian Long-Chain Acyl-CoA Synthetases

Soupène¹,

Kuypers²

2008

Exp Biol Med (Maywood)

374

324

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Acyl-CoA synthetase enzymes are essential for de novo lipid synthesis, fatty acid catabolism, and remodeling of membranes. Activation of fatty acids requires a two-step reaction catalyzed by these enzymes. In the first step, an acyl-AMP intermediate is formed from ATP. AMP is then exchanged with CoA to produce the activated acyl-CoA. The release of AMP in this reaction defines the superfamily of AMP-forming enzymes. The length of the carbon chain of the fatty acid species defines the substrate specificity for the different acyl-CoA synthetases (ACS). On this basis, five sub-families of ACS have been characterized. The purpose of this review is to report on the large family of mammalian long-chain acyl-CoA synthetases (ACSL), which activate fatty acids with chain lengths of 12 to 20 carbon atoms. Five genes and several isoforms generated by alternative splicing have been identified and limited information is available on their localization. The structure of these membrane proteins has not been solved for the mammalian ACSLs but homology to a bacterial form, whose structure has been determined, points at specific structural features that are important for these enzymes across species. The bacterial form acts as a dimer and has a conserved short motif, called the fatty acid Gate domain, that seems to determine substrate specificity. We will discuss the characterization and identification of the different spliced isoforms, draw attention to the inconsistencies and errors in their annotations, and their cellular localizations. These membrane proteins act on membrane-bound substrates probably as homo-and as heterodimer complexes but have often been expressed as single recombinant isoforms, apparently purified as monomers and tested in Triton X-100 micelles. We will argue that such studies have failed to provide an accurate assessment of the activity and of the distinct function of these enzymes in mammalian cells.

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“…Activation of fatty acids by acylCoA synthetases also involves activation of fatty acids by ATP to form acylAMP. Homology between these enzymes has been reported (Suzuki et al, 1990;Babbitt et al, 1992;Ye et al, 1997). It is not surprising that myristate competes with luciferin.…”

Section: Introductionmentioning

confidence: 98%

Does Pressure Antagonize Anesthesia? Opposite Effects on Specific and Nonspecific Inhibitors of Firefly Luciferase

Ueda

Matsuki

Kamaya

et al. 1999

Biophysical Journal

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Ueda and Suzuki (1998. Biochim. Biophys. Acta. 1380:313-319; 1998. Biophys. J. 75:1052-1057) reported that myristic acid inhibited firefly luciferase in microM range in competition with luciferin, whereas anesthetics inhibited it in millimeter ranges noncompetitively with luciferin. Myristate increased, whereas anesthetics decreased, the thermal denaturation temperature. The present study showed that high pressure increased the steady-state light intensity of the halothane-doped firefly luciferase but decreased that of the myristate-doped firefly luciferase. The steady-state light intensity showed a maximum at 19.1 degrees C. At 19.1 degrees C, high pressure did not affect the light intensity in the absence of the inhibitors. In the presence of 0.5 mM halothane, however, 25 MPa pressure (maximum effect) increased the light intensity to 106.0% of the control without the inhibitor. In the presence of 2.5 microM myristate, 40 MPa pressure decreased the light intensity to 90.9% of the control. When the temperature was 25 degrees C in the absence of inhibitors, 40 MPa pressure increased the light intensity 119.2% of the ambient value. At 0.5 mM halothane, 40 MPa pressure further increased the light intensity to 106.1% above the control 40 MPa value. At 2.5 microM myristate, 40 MPa pressure decreased the light intensity to 90.1% of the control 40 MPa value. From the pressure dependence of the light intensity, the volume change DeltaV of the enzyme was estimated at 25 degrees C: 0.5 mM halothane increased DeltaV = +3.93 cm3 mol-1, whereas 2.5 microM myristate decreased DeltaV = -7.66 cm3 mol-1. Present results show that there are distinct differences between the specific and nonspecific ligands in their response to high pressure. Myristate, which competes with luciferin, decreased the protein volume and stabilized the conformation against thermal perturbation. Halothane, which does not compete with the substrate, increased the protein volume and destabilized the conformation.

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Structure and regulation of rat long-chain acyl-CoA synthetase.

Cited by 331 publications

References 24 publications

The Complex Tail of Circulating Sphingolipids in Atherosclerosis and Cardiovascular Disease

The Complex Tail of Circulating Sphingolipids in Atherosclerosis and Cardiovascular Disease

Mammalian Long-Chain Acyl-CoA Synthetases

Does Pressure Antagonize Anesthesia? Opposite Effects on Specific and Nonspecific Inhibitors of Firefly Luciferase

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