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ACSL1

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

Acyl-CoA synthetase long-chain family member 1 (ACSL1) is a membrane-bound enzyme that catalyzes the ATP-dependent ligation of long-chain fatty acids with coenzyme A, generating fatty acyl-CoA esters–the essential activated intermediates and entry-point substrates for virtually all downstream fatty acid utilization pathways. ACSL1 catalysis occurs through a two-step bi-bi mechanism: first, the carboxyl group of the fatty acid attacks the α-phosphate of ATP to generate a fat acyl-adenosine monophosphate (acyl-AMP) intermediate with concurrent release of pyrophosphate; second, coenzyme A thiol nucleophilically attacks an acyl-AMP intermediate which displaces AMP, generating the final product fatty acyl-CoA. The aforementioned activation step is the first conversion, and thus plays a central role in providing appropriate intracellular acyl-CoAs to serve as metabolic intermediates that enable fatty acid metabolism, including mitochondrial β-oxidation pathway, triglyceride synthesis, phospholipid biosynthesis, cholesterol esterification, protein acylation and fatty-acid dependent transcriptional regulation. Details: ACSL1 is highly expressed in metabolically active tissues such as liver, adipose tissue and heart, while it accounts for about 80% of total ACSL enzymatic activity to be found in the adipose tissue. It is targeted to the outer mitochondrial membrane, endoplasmic reticulum and plasma membrane by an N-terminal transmembrane helix that securely anchors it in cellular membranes and helps determine the metabolic fate of activated fatty acids.

Fig.1 Fatty acid (FA) metabolism via ACSL1. (OA Literature)Fig.1 Diagram for fatty acid (FA) metabolism.1

ACSL1 Protein Function: A Hub of Cellular Regulation

Functional repertoire with respect to ACSL1 shows that its roles span lipid metabolism-energy homeostasis-disease pathogenesis triad dimensions:

  • Mitochondrial Fatty Acid Oxidation and Metabolic Channeling: ACS lean more than other ACSL family members, is the only major gatekeeping enzyme for directing activated fatty acids into mitochondrial β-oxidation(10). In adipose tissue, ACSL1 is tethered to the outer mitochondrial membrane via a direct interaction between its N-terminal domain and the rate-limiting enzyme for fatty acid entry into mitochondria.
  • Cold Thermogenesis and Adaptive Energy Expenditure: The essential role of ACSL1 during adaptive thermogenesis was illustrated by the cold intolerance phenotype in adipose-specific Acsl1 knockout (KO) mice. Although UCP1 was expressed in brown adipose tissue and both normal adrenergic signaling and lipolysis occurred, when these mice were placed at 4°C the body temperature of animals with a body temperature of less than 30°C fell after only 2-5 hours suggesting hypothermia developed rapidly causing death within this period.
  • TBK1-Dependent Subcellular Trafficking and Nutritional Sensing: TBK1 dynamically regulates the subcellular localization of ACSL1 within cells, and TBK1 also acts as a scaffolding protein to recruit ACSL1 for translocation into mitochondria in models of fasting. TBK1 is induced in the fasted state, but it can also be present in a dephosphorylated inactive form which has high-affinity binding to ACSL1 and sequesters this enzyme or potentially p62. As a result of obesity phosphorylated active TBK1 can dissociate from mitochondria leading to decreased affinity for mitochondrial ACSL1 and increased trafficking of ACSL1 into the endoplasmic reticulum where it serves as a catalyzing agent for Triglycerides synthesis via re-esterification of fatty acids instead of oxidation.

ACSL1 Membrane Protein Product

ACSL1 membrane protein products are provided in our selection of quality ACSL1 membrane proteins for structural and functional studies of this fatty acid-activating enzyme. Our recombinant membrane protein technology supports the production of ACSL1 in formats suitable for a range of research applications. As a membrane-associated enzyme, ACSL1 may require appropriate protein topology and membrane-associated conditions for certain functional studies, so our portfolio includes constructs designed for different experimental needs. Available products may include purified or membrane-associated formats suitable for biochemical, structural, binding, and functional analyses. Wild-type and other research-use ACSL1 constructs may also be available depending on the specific product.

ACSL1 Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

ACSL1 Stable Cell Line Product

Although relevant cellular models are essential to basic research on ACSL1, the multifaceted function of this metabolic enzyme in fatty acid metabolism and pathway regulation underscores the need for reliable cellular research tools. We offer custom-engineered ACSL1 stable cell lines designed to provide consistent target expression for a range of research applications. Depending on experimental requirements, cell lines with different ACSL1 expression formats may be available for studies of fatty acid metabolism, lipid accumulation, pathway regulation, and compound screening. Our stable cell line development platform supports customized cell models with appropriate expression strategies and quality assessment to meet specific research needs.

ACSL1 Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

ACSL1 Recombinant Antibody Product

We offer a wide range of high-affinity recombinant antibodies against ACSL1 for diverse research applications. Recombinant production can provide consistent antibody performance and lot-to-lot reproducibility for routine research use. Depending on the specific product, ACSL1 recombinant antibodies may be suitable or available for selected applications such as Western Blotting (WB), Immunohistochemistry (IHC), Immunofluorescence (IF), Flow Cytometry (FCM), and other antibody-based assays. These antibodies can support the detection and analysis of ACSL1 expression, localization, and related biological processes in appropriate research samples and model systems.

ACSL1 Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • High Purity & Activity: High purity and verified integrity for dependable downstream work.
  • Diverse Expression Systems: Choice of expression formats to match routine or specialized projects.
  • Species Reactivity: Products available for human, mouse, pig, and other species.
  • Validated Applications: Application-tested to deliver consistent signals across common lab workflows.
  • Exceptional Lot-to-Lot Consistency: Tight lot-to-lot control for reproducible performance.
  • Customization Options: Flexible customization of tags, labels, or packaging upon request.

Custom ACSL1 Membrane Protein and Antibody Discovery Services

In addition to product catalog, we also provide specialized custom services in the membrane protein and antibody discovery & development area. Based on our decade of expertise and sophisticated platforms we can assist you with:

  • Custom ACSL1 Receptor Production: Tailored expression, purification, and characterization of challenging multi-domain receptor constructs.
  • Custom Antibody Development: From antigen design to antibody engineering (monoclonal, polyclonal, recombinant) for specific research applications.
  • Stable Cell Line Development: Generation of bespoke stable cell lines expressing your target of interest.
  • Functional Assay Development: Designing and executing assays to assess receptor activation and ligand.

Frequently Asked Questions (FAQ)

  1. Did you test application of your anti-ACSL1 antibodies for immunofluorescence staining to paraformaldehyde-fixed hepatocyte cultures, adipose tissue cryosections or skeletal muscle cross-sections to visualize both membrane recruitment and lipid droplet association?

    Yes, some clones have been validated on lightly fixed hepatocyte-lineage cultures and tissue cryosections with perinuclear and endoplasmic reticulum staining that becomes stronger with oleate exposure and co-localizes to lipid droplet stains upon confocal microscopy. In muscle fragments, the staining changes from diffuse cytoplasmic in basal states to membrane-associated punctate after fatty acid loading.

  2. Are the reagents and service provided for diagnostic testing or for therapeutic?

    No, all reagents and services provided are designated solely for research purposes and cannot be used for diagnostic testing or therapeutic purposes.

  3. Do you have a stable and doxycycline-induced ACSL1 expression in your stable cell lines needed to temporally model fatty acid uptake or lipid droplet biogenesis or even the flux kinetics of metabolism?

    Yes, we have made stable lines for those and these are under the control of a doxycycline-operated promoter in A2780 cells. This allows for timed expression initiation at defined intervals and subsequent measurement of palmitate tracing, triacylglycerol accumulation, and mitochondrial β-oxidation flux with a temporal resolution all in the absence of metabolic adaptation artifacts that characterize traditional constitutive overexpression systems.

  4. Are there ACSL1 variants given in the literature, each bearing a mutation located at either the catalytic-center or the fatty acid-binding pocket that can be contrasted for enzymatic profiling, lipid metabolism exploration and substrate specificity examinations?

    Yes, we provide recombinant proteins and stable cell lines for some characterized variants where active site residues that contribute to AMP-formation or acyl-chain selectivity determinants are disrupted. These materials are important specificity control reagents for deciphering the relative contributions of adenylation chemistry vs. thioesterification efficiency, and chain-length preference vs. membrane affinity to cellular partitioning of fatty acids and energy homeostasis.

Reference
  1. Wu, Zhimin, et al. "An update on the therapeutic implications of long-chain acyl-coenzyme A synthetases in nervous system diseases." Frontiers in Neuroscience 16 (2022): 1030512. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.3389/fnins.2022.1030512
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