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Target intelligence / Profile preview
Long-chain-fatty-acid--CoA ligase
- Molecular classification
- Enzyme, Ligase, Acyl-CoA synthetase (specific enzyme within the EC 6.2.1.3 family)
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Overview
Long-chain-fatty-acid--CoA ligase is an enzyme (EC 6.2.1.3) critical for fatty acid metabolism, catalyzing the ATP-dependent activation of long-chain fatty acids (typically 12–20 carbons) by converting them into their CoA thioesters (fatty acyl-CoA). This step is essential for subsequent fatty acid β-oxidation, lipid biosynthesis, and membrane remodeling. The enzyme is widely expressed from bacteria to humans and is encoded by distinct genes (notably ACSL family isoforms in mammals), with tissue-, substrate-, and isoform-specific functions. It controls cellular fatty acid utilization, regulates cell proliferation and apoptosis, and is implicated in metabolic diseases, liver conditions, cancer biology, and neurological disorders. Pharmacological modulation remains largely experimental, but its role as a metabolic gatekeeper and disease biomarker is well established in the literature.
- Other names
- Long chain fatty acyl-CoA synthetaseAcyl-CoA synthetaseFatty acid thiokinase (long chain)Acyl-activating enzymeLignoceroyl-CoA synthaseACSL (family)
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Mechanism of action
Drugs modulate this enzyme’s activity by inhibition or activation of fatty acid activation step, thus affecting via metabolic fate (e.g., blocking beta-oxidation or channeling fatty acids to other pathways)
03
Biological functions
Fatty acid activation (conversion of fatty acids to fatty acyl-CoA thioesters)Fatty acid metabolism (including β-oxidation, lipid synthesis, membrane modifications)Regulation of protein transport, enzyme activation, protein acylation, cell signaling, and transcriptional regulationCell proliferation and apoptosis regulation
04
Disease associations
Metabolic diseases (diabetes, obesity, fatty liver disease, atherosclerosis)Liver diseasesCancer (notably, ACSL4 is implicated as a biomarker and driver in hormone-resistant breast cancer)Neurological disordersOther (broad role in lipid and metabolic homeostasis)
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Safety considerations
Disruption of fatty acid metabolism may lead to metabolic imbalances.Systemic inhibition or activation may have broad lipidomic and cellular effects, risking steatosis, lipotoxicity, or other alterations in energy homeostasis
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Interacting drugs
No specific drugs are universally approved for this class; individual isoforms (e.g., ACSL4 inhibitors/activators) are in preclinical and research stages, and fatty acid analogs or metabolic modulators may interact with ACSL enzymes
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Biomarkers
Long-chain acyl-CoA synthetase 4 (ACSL4) protein is identified as a biomarker for hormone resistance in breast cancer and potentially prognostic in other metabolic/liver diseases
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