ACSL4 Antibodies

Background

ACSL4 is an enzyme protein located in the cytoplasmic membrane, mainly distributed in tissues such as the liver, brain, and reproductive system. This enzyme catalyzes the reaction of combining long-chain fatty acids with coenzyme A, participating in lipid metabolism, membrane phospholipid remodeling, and the biosynthesis process of ceramide-like signaling molecules. The activity regulation of ACSL4 is dependent on cellular energy homeostasis and inflammatory response, especially in the ferroptosis pathway, where this enzyme directly affects the sensitivity of cell membrane lipid peroxidation by promoting the esterification reaction of polyunsaturated fatty acids. Gene mutations of ACSL4 are associated with neurodevelopmental abnormalities such as intellectual disability, epilepsy, and Alpers syndrome. In recent years, it has also been found to play a key role in tumor metabolic reprogramming. The research on the structure and function of ACSL4 continues to reveal the molecular mechanism of lipid metabolism in cell fate determination, providing a new perspective for the treatment of metabolic diseases and tumors.

Structure Function Application Advantage Our Products

Structure of ACSL4

ACSL4 (long-chain acyl-CoA synthetase 4) is an enzyme protein with a molecular weight of approximately 78 kDa. This weight may vary slightly depending on different subtypes or post-translational modifications.

Species	Human	Mouse	Rat
Molecular Weight (kDa)	77.8	78.1	77.9
Primary Structural Differences	Having multiple variable splicing elements, with a highly conserved structure	Has an extremely high sequence homology with humans	The core catalytic domain is exactly the same

This protein is composed of approximately 700 amino acids and its primary structure folds into a compact spherical structure containing two core domains (adenosine triphosphate formation domain and fatty acid binding domain). The key feature of the structure of the ACS4 protein is the central ATP binding pocket (Walker A motif), which drives the activation of fatty acids by forming an acyl-adenosine intermediate. The palmitoylation modification site of the enzyme is located at the N-terminus, affecting its membrane localization. Its active site is composed of highly conserved arginine (responsible for binding to the phosphate group of ATP) and histidine (involved in proton transfer during the catalytic process), which jointly coordinate substrate specificity and stabilize the reaction transition state.

Fig. 1 Molecular docking performed the binding pose details between PrA and ACSL4.¹

Key structural properties of ACSL4:

Transmembrane helix and membrane-anchoring domain
Conservative ATP/AMP binding pocket (adenosine acid formation domain)
Long-chain fatty acid substrate channels and binding sites
The key amino acids at the active site are involved in the formation and stabilization of the acyl-adenosine intermediate.

Functions of ACSL4

The main function of the protein encoded by the ACSL4 gene is to catalyze the activation of long-chain fatty acids, which is a crucial initial step in lipid metabolism. Additionally, it is involved in various physiological and pathological processes such as membrane phospholipid remodeling, cell signal transduction, and maintenance of energy homeostasis.

Function	Description
Fatty Acid Activation	Catalyzes the combination of long-chain fatty acids with coenzyme A to form fatty acyl coenzyme A, providing a substrate for subsequent β-oxidation or esterification reactions.
Membrane Phospholipid Remodeling	By providing specific polyunsaturated fatty acyl coenzyme A substrates, it participates in the renewal of the fatty acid chain composition of cell membrane phospholipids (such as phosphatidylethanolamine).
Regulation of Ferroptosis	It is a key positive regulatory factor for ferroptosis (a type of iron-dependent programmed cell death), and its activity and products directly promote lipid peroxidation.
Synthesis of Twenty-alkanoic Acid	It provides activated substrates for the metabolism of precursor molecules such as arachidonic acid, influencing the biosynthesis of inflammatory mediators such as prostaglandins and leukotrienes.
Energy Metabolism and Storage	By directing fatty acids into the oxidation pathway or the synthesis of triglycerides, it regulates the balance between energy supply within cells and lipid storage.

Unlike single-functional oxygen carriers, the substrate preference and subcellular localization of ACSL4 determine its guiding role in metabolic flux. Its specific activation of polyunsaturated fatty acids such as arachidonic acid enables it to play a unique "metabolic switch" role in inflammatory and cell death signaling pathways.

Applications of ACSL4 and ACSL4 Antibody in Literature

1. Yang, Yufei, et al. "ACSL3 and ACSL4, distinct roles in ferroptosis and cancers." Cancers 14.23 (2022): 5896. https://doi.org/10.3390/cancers14235896

The article indicates that ACSL3 and ACSL4 are members of the long-chain fatty acid coenzyme A synthase family. They participate in various cancer processes by influencing lipid metabolism and ferroptosis. The regulatory mechanism of these enzymes holds promise for providing new strategies for targeted tumor therapy.

2. Zeng, Kaixuan, et al. "Inhibition of CDK1 overcomes Oxaliplatin resistance by regulating ACSL4‐mediated Ferroptosis in colorectal cancer." Advanced Science 10.25 (2023): 2301088. https://doi.org/10.1002/advs.202301088

The research reveals that CDK1 phosphorylates ACSL4 and promotes its ubiquitination and degradation, thereby inhibiting lipid peroxidation and ferroptosis, and leading to the resistance of colorectal cancer to oxaliplatin. Targeting CDK1 can restore drug sensitivity.

3. Tuo, Qing-zhang, et al. "Thrombin induces ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion." Signal transduction and targeted therapy 7.1 (2022): 59. https://doi.org/10.1038/s41392-022-00917-z

This study reveals that thrombin, by activating ACSL4, promotes arachidonic acid metabolism and lipid peroxidation, thereby driving neuronal ferroptosis after ischemic stroke. Targeted inhibition of this pathway can alleviate nerve damage and provides a new strategy for treatment.

4. Cui, Jingxuan, et al. "Protosappanin A protects DOX‐induced myocardial injury and cardiac dysfunction by targeting ACSL4/FTH1 axis‐dependent ferroptosis." Advanced Science 11.34 (2024): 2310227. https://doi.org/10.1002/advs.202310227

This study reveals that PrA derived from hematoxylin directly binds to ACSL4 and FTH1, inhibiting lipid peroxidation and iron ion release, thereby blocking ferroptosis and providing a new target and strategy for the prevention and treatment of anthracycline-induced cardiac toxicity.

5. Feng, Shengjie, et al. "Inhibition of CARM1‐mediated methylation of ACSL4 promotes ferroptosis in colorectal cancer." Advanced Science 10.36 (2023): 2303484. https://doi.org/10.1002/advs.202303484

The research has found that CARM1 methylates the R339 site of ACSL4, promoting its ubiquitination and degradation, thereby inhibiting ferroptosis. Blocking CARM1 can enhance the sensitivity of tumor cells to ferroptosis, providing a new strategy for cancer immunotherapy.

Creative Biolabs: ACSL4 Antibodies for Research

Creative Biolabs specializes in the production of high-quality ACSL4 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom ACSL4 Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our ACSL4 antibodies, custom preparations, or technical support, contact us at email.

Reference

Cui, Jingxuan, et al. "Protosappanin A protects DOX‐induced myocardial injury and cardiac dysfunction by targeting ACSL4/FTH1 axis‐dependent ferroptosis." Advanced Science 11.34 (2024): 2310227. https://doi.org/10.1002/advs.202310227