Acyl-CoA Thioesterases in Lipid Metabolism Dynamics
Summary
Acyl-CoA thioesterases (ACOTs) are a family of enzymes that hydrolyse fatty acyl-CoA esters to free fatty acids and coenzyme A, thereby governing intracellular acyl-CoA pools and maintaining CoA availability for essential metabolic pathways. Through a combination of cytosolic, peroxisomal and mitochondrial isoforms, ACOTs modulate lipid synthesis, β-oxidation and signalling lipid levels. In mitochondria, specific thioesterases prevent overload of β-oxidation by siphoning long-chain acyl-CoAs when CoA is limiting, while in liver and adipose tissues tissue-selective ACOT expression adapts to nutritional or hormonal cues. Dysregulated ACOT activity has been implicated in metabolic disorders, inflammation and cancer, highlighting their potential as therapeutic targets. Recent advances in structural characterisation and genetic manipulation have begun to reveal isoform-specific roles in energy homeostasis and lipid signalling dynamics across tissues.
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Acyl-CoA Thioesterases in Lipid Metabolism Dynamics publication trend
The graph below shows the total number of articles in acyl-coa thioesterases in lipid metabolism dynamics across all publications each year (not limited to Nature Index journals).
Technical terms
Acyl-CoA thioesterase (ACOT): Enzyme that hydrolyses the thioester bond of fatty acyl-CoA esters, yielding free fatty acids and CoA.
β-oxidation: Mitochondrial process by which fatty acyl-CoAs are sequentially degraded to acetyl-CoA units for energy production.
Coenzyme A (CoA): Essential cofactor that carries acyl groups in metabolic reactions, including lipid synthesis and degradation.
Lipidome: The complete set of lipid species within a cell or tissue, reflecting metabolic and signalling states.
Free fatty acid (FFA): Unesterified fatty acid released by lipolysis or thioesterase activity, utilised in membrane synthesis, signalling or energy generation.
References
- Evolutionary divergence and functions of the human acyl-CoA thioesterase gene (ACOT) family. Human Genomics (2010).
- Metabolic and Tissue-Specific Regulation of Acyl-CoA Metabolism. PLOS ONE (2015).
- Multiple mitochondrial thioesterases have distinct tissue and substrate specificity and CoA regulation, suggesting unique functional roles. Journal of Biological Chemistry (2019).
- Inflammatory stimuli induce acyl-CoA thioesterase 7 and remodeling of phospholipids containing unsaturated long (≥C20)-acyl chains in macrophages[S]. Journal of Lipid Research (2017).
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