GO:0003986 acetyl-CoA hydrolase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0003986 acetyl-CoA hydrolase activity catalyzes the hydrolysis of acetyl-CoA to acetate, CoA, and H+, regulating cellular acetyl-CoA pools.
• The enzyme is conserved from yeast to mammals, with yeast Ach1p being a well-characterized example involved in acetate utilization.
• In mammals, acetyl-CoA hydrolase activity influences cholesterol metabolism and lipid biosynthesis, with implications for metabolic diseases.
• Dysregulation of acetyl-CoA hydrolase activity is linked to non-alcoholic fatty liver disease, hepatocarcinogenesis, and osteoarthritis.
• Research models include yeast and mammalian cell lines, with CRISPR knockout, point mutation, and overexpression enabling functional studies.
• Key methods to study this activity include enzyme assays, metabolomics, and CRISPR-based screens to identify regulatory networks.
Description
Acetyl-CoA hydrolase activity (GO:0003986) is a molecular function that catalyzes the hydrolysis of acetyl-coenzyme A (acetyl-CoA) into acetate, coenzyme A (CoA), and a proton. This reaction is critical for maintaining cellular acetyl-CoA homeostasis, as acetyl-CoA is a central metabolite at the intersection of carbohydrate, lipid, and amino acid metabolism. By regulating acetyl-CoA levels, this enzyme influences diverse processes such as energy production, lipid synthesis, and protein acetylation. In eukaryotic cells, acetyl-CoA hydrolase activity has been identified in various compartments, including mitochondria and cytosol, where it modulates metabolic flux. The enzyme is conserved across species, with yeast Ach1p serving as a paradigm for understanding its role in acetate utilization and metabolic adaptation. In mammals, acetyl-CoA hydrolase activity has been implicated in cholesterol metabolism and lipid biosynthesis, highlighting its importance in metabolic regulation. Given its central role in metabolism, acetyl-CoA hydrolase activity is a subject of intense research, with implications for diseases such as non-alcoholic fatty liver disease (NAFLD), cancer, and osteoarthritis. Understanding this activity at the molecular level provides insights into metabolic reprogramming and potential therapeutic targets.
acetyl-CoA hydrolase activity At A Glance
| GO ID | GO:0003986 |
|---|---|
| GO term | acetyl-CoA hydrolase activity |
| Ontology | molecular_function |
| Synonym | acetyl-CoA acylase activity, acetyl-CoA deacylase activity, acetyl-CoA thiol esterase activity, acetyl coenzyme A acylase activity, acetyl coenzyme A deacylase activity, acetyl coenzyme A hydrolase activity |
| Definition | Catalysis of the reaction: acetyl-CoA + H2O = acetate + CoA + H+ |
| Major function | Regulation of acetyl-CoA homeostasis by hydrolyzing acetyl-CoA to acetate and CoA |
| EC number | 3.1.2.1 |
| Reaction direction | Irreversible hydrolysis |
| Subcellular location | Mitochondria, cytosol (varies by organism) |
What Is GO:0003986?
According to the Gene Ontology, acetyl-CoA hydrolase activity (GO:0003986) is defined as the catalysis of the reaction: acetyl-CoA + H2O = acetate + CoA + H+. This enzymatic activity belongs to the molecular function ontology and is synonymous with terms such as acetyl-CoA acylase activity, acetyl-CoA deacylase activity, and acetyl-CoA thiol esterase activity. It specifically hydrolyzes the thioester bond in acetyl-CoA, releasing free CoA and acetate, thereby regulating the pool of acetyl-CoA available for biosynthetic and bioenergetic pathways.
Why Is acetyl-CoA hydrolase activity Important in Cell Biology?
Acetyl-CoA hydrolase activity is fundamentally important because acetyl-CoA is a pivotal metabolite that fuels the tricarboxylic acid (TCA) cycle, serves as a precursor for lipid synthesis, and acts as an acetyl donor for protein acetylation. By controlling acetyl-CoA levels, this enzyme directly impacts energy metabolism, lipid homeostasis, and gene regulation. Dysregulation of acetyl-CoA hydrolase activity has been associated with metabolic disorders such as NAFLD, where altered cholesterol and bile acid metabolism contribute to disease progression. In cancer, acetyl-CoA hydrolase activity can suppress hepatocarcinogenesis by limiting glycerolipid biosynthesis, highlighting its tumor-suppressive potential. Furthermore, in osteoarthritis, metabolic shifts involving acetyl-CoA may influence cartilage degradation and inflammation. Thus, understanding acetyl-CoA hydrolase activity is crucial for developing therapeutic strategies targeting metabolic diseases and cancer.
• Regulates acetyl-CoA pools, affecting TCA cycle flux and energy production.
• Modulates lipid biosynthesis, including cholesterol and glycerolipids, with implications for NAFLD and cancer.
• Influences protein acetylation by controlling acetyl-CoA availability, impacting gene expression.
• Plays a role in acetate utilization in yeast and potentially in mammalian metabolism.
• Linked to osteoarthritis pathogenesis through metabolic reprogramming.
• Serves as a potential therapeutic target for metabolic disorders and cancer.
• Conserved across species, enabling comparative studies in model organisms.
• Can be studied using CRISPR screens to identify regulatory networks.
• Involved in brain metabolism, where acetyl-CoA distribution is critical for neurotransmitter synthesis.
• Provides a mechanism for cells to adapt to metabolic stress by adjusting acetyl-CoA levels.
What Happens During acetyl-CoA hydrolase activity?
Substrate Binding and Hydrolysis
In simple terms: The enzyme grabs acetyl-CoA and breaks it apart using water.
Acetyl-CoA hydrolase binds its substrate, acetyl-CoA, in the active site. The enzyme catalyzes the hydrolysis of the thioester bond between the acetyl group and coenzyme A, using a water molecule. This reaction yields acetate, free CoA, and a proton. The catalytic mechanism typically involves a catalytic triad or a metal ion cofactor, although specific residues vary among enzymes from different organisms. In yeast Ach1p, the enzyme is localized to the cytosol and mitochondria and is essential for acetate utilization during growth on non-fermentable carbon sources.
Regulation of Acetyl-CoA Homeostasis
In simple terms: By breaking down acetyl-CoA, the enzyme controls how much acetyl-CoA is available for other processes.
The hydrolysis of acetyl-CoA directly reduces the cellular pool of this key metabolite. This regulation is critical because acetyl-CoA is a central node in metabolism, feeding into the TCA cycle, lipid synthesis, and protein acetylation. In mammals, acetyl-CoA hydrolase activity in the liver influences cholesterol metabolism, as shown by studies in rats where enzyme activity correlated with changes in cholesterol synthesis. In cancer cells, acyl-CoA thioesterase 12 (ACOT12), which possesses acetyl-CoA hydrolase activity, suppresses YAP-mediated hepatocarcinogenesis by limiting glycerolipid biosynthesis. Thus, the enzyme acts as a metabolic brake, preventing excessive acetyl-CoA accumulation that could drive pathological lipid synthesis.
Role in Acetate Utilization and Energy Metabolism
In simple terms: In some organisms, the enzyme helps generate acetate that can be used for energy.
In Saccharomyces cerevisiae, acetyl-CoA hydrolase Ach1p is involved in acetate utilization, allowing cells to grow on acetate as a carbon source. The enzyme converts acetyl-CoA to acetate, which can then be activated to acetyl-CoA by acetyl-CoA synthetase, or excreted. This pathway is important for metabolic flexibility. In Ascaris suum muscle mitochondria, acetyl-CoA hydrolase activity contributes to energy metabolism by regulating acetyl-CoA levels. In the brain, acetyl-CoA distribution is tightly regulated, and hydrolase activity may influence neurotransmitter acetylcholine synthesis.
Impact on Lipid Biosynthesis
In simple terms: The enzyme controls the raw material for making fats.
Acetyl-CoA is the primary building block for fatty acid and cholesterol synthesis. By hydrolyzing acetyl-CoA, acetyl-CoA hydrolase activity reduces the substrate available for these anabolic pathways. In hepatocytes, decreased acetyl-CoA hydrolase activity can lead to increased glycerolipid biosynthesis, promoting hepatocarcinogenesis. Conversely, upregulation of the enzyme may limit lipid accumulation, as observed in NAFLD models where hyperoside treatment modulated cholesterol and bile acid metabolism, potentially involving acetyl-CoA hydrolase. This role makes the enzyme a key regulator of lipid homeostasis.
Subcellular Compartmentalization
In simple terms: The enzyme works in different parts of the cell, depending on the organism.
Acetyl-CoA hydrolase activity has been detected in multiple subcellular compartments. In yeast, Ach1p is found in both cytosol and mitochondria, with distinct roles in acetate utilization and energy metabolism. In mammals, acetyl-CoA hydrolase activity is present in mitochondria and cytosol, where it regulates compartment-specific acetyl-CoA pools. This compartmentalization allows the enzyme to fine-tune acetyl-CoA levels for local metabolic needs, such as mitochondrial oxidation or cytosolic lipid synthesis.
Key Genes Involved in GO:0003986 acetyl-CoA hydrolase activity
The following genes and proteins are directly associated with acetyl-CoA hydrolase activity (GO:0003986) or its regulation, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ACH1 (Saccharomyces cerevisiae) | Acetyl-CoA hydrolase; involved in acetate utilization | Model for studying enzyme function and metabolic adaptation |
| ACOT12 (human) | Acyl-CoA thioesterase 12; exhibits acetyl-CoA hydrolase activity | Suppresses hepatocarcinogenesis by limiting glycerolipid biosynthesis |
| ACOT1 (human) | Acyl-CoA thioesterase 1; broad specificity including acetyl-CoA | Regulates lipid metabolism and peroxisomal beta-oxidation |
| ACOT2 (human) | Mitochondrial acyl-CoA thioesterase | Involved in fatty acid oxidation and energy homeostasis |
| ACOT7 (human) | Cytosolic acyl-CoA thioesterase | Regulates acetyl-CoA levels for lipid synthesis |
| ACOT8 (human) | Peroxisomal acyl-CoA thioesterase | Participates in peroxisomal lipid metabolism |
| ACOT9 (human) | Mitochondrial acyl-CoA thioesterase | Linked to metabolic regulation |
| ACOT11 (human) | Acyl-CoA thioesterase 11 | Associated with obesity and insulin resistance |
| ACOT13 (human) | Acyl-CoA thioesterase 13 | Involved in lipid metabolism |
| THEM4 (human) | Acyl-CoA thioesterase | Regulates AKT signaling and metabolism |
| THEM5 (human) | Acyl-CoA thioesterase | Potential role in metabolic diseases |
| BACH1 (human) | BTB domain and CNC homolog 1 | Transcription factor regulating ACOT12 expression |
| YAP1 (human) | Yes-associated protein 1 | Downstream effector suppressed by ACOT12 |
| SREBF1 (human) | Sterol regulatory element binding transcription factor 1 | Regulates lipid synthesis genes, crosstalk with acetyl-CoA metabolism |
| NR1H4 (human) | Nuclear receptor subfamily 1 group H member 4 (FXR) | Regulates bile acid and cholesterol metabolism, linked to acetyl-CoA hydrolase |
| CYP7A1 (human) | Cytochrome P450 family 7 subfamily A member 1 | Cholesterol 7-alpha-hydroxylase, affected by acetyl-CoA hydrolase activity |
| HMGCR (human) | 3-hydroxy-3-methylglutaryl-CoA reductase | Cholesterol synthesis, regulated by acetyl-CoA availability |
How Is acetyl-CoA hydrolase activity Regulated?
Acetyl-CoA hydrolase activity is regulated at multiple levels. In yeast, ACH1 expression is induced by growth on acetate or non-fermentable carbon sources, mediated by transcription factors such as Adr1p and Cat8p. In mammals, ACOT12 expression is regulated by the transcription factor BACH1, which represses ACOT12, leading to increased acetyl-CoA levels and YAP activation in hepatocarcinogenesis. Additionally, the activity of acetyl-CoA hydrolase can be modulated by post-translational modifications and metabolite availability. For example, in the brain, acetyl-CoA distribution is regulated by enzymes including acetyl-CoA hydrolase, which responds to changes in energy status. Hormonal signals, such as insulin, may also influence acetyl-CoA hydrolase activity, as suggested by studies linking it to cholesterol metabolism in rats. Overall, regulation ensures that acetyl-CoA levels are maintained within a narrow range to support cellular functions.
acetyl-CoA hydrolase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ACOT12 | Hepatocarcinogenesis | Liver-specific knockout mice, HCC cell lines |
| ACH1 | Metabolic adaptation in yeast | Saccharomyces cerevisiae deletion strains |
| ACOT1 | NAFLD, lipid metabolism | High-fat diet-fed knockout mice |
| ACOT7 | Brain metabolism, neurotransmitter synthesis | Neuronal-specific knockout mice |
| ACOT11 | Obesity, insulin resistance | Adipose-specific overexpression mice |
Non-Alcoholic Fatty Liver Disease (NAFLD)
Acetyl-CoA hydrolase activity is implicated in NAFLD through its role in cholesterol and bile acid metabolism. In a rat model of NAFLD, hyperoside treatment attenuated disease progression by modulating cholesterol metabolism and bile acid metabolism, potentially involving changes in acetyl-CoA hydrolase activity. The enzyme's ability to regulate acetyl-CoA pools affects lipid synthesis, and its dysregulation may contribute to hepatic steatosis. Furthermore, ACOT12, which possesses acetyl-CoA hydrolase activity, suppresses hepatocarcinogenesis by limiting glycerolipid biosynthesis, suggesting that loss of this activity promotes liver cancer. Thus, targeting acetyl-CoA hydrolase activity could be a therapeutic strategy for NAFLD and related liver diseases.
Hepatocarcinogenesis
ACOT12, an acyl-CoA thioesterase with acetyl-CoA hydrolase activity, functions as a tumor suppressor in hepatocellular carcinoma (HCC). Its downregulation leads to increased acetyl-CoA levels, which fuel glycerolipid biosynthesis and activate YAP-mediated oncogenic signaling. This highlights the critical role of acetyl-CoA hydrolase activity in preventing metabolic reprogramming that supports cancer growth. Restoring ACOT12 activity or inhibiting downstream lipid synthesis pathways could offer new avenues for HCC treatment.
Osteoarthritis
Metabolic alterations in osteoarthritis include changes in acetyl-CoA metabolism. A review of osteoarthritis biology in 2022 highlighted the importance of metabolic pathways in cartilage degradation and inflammation. Although direct evidence for acetyl-CoA hydrolase activity in osteoarthritis is limited, the enzyme's role in regulating acetyl-CoA levels may influence chondrocyte function and matrix synthesis. Further research is needed to establish a direct link, but targeting metabolic enzymes like acetyl-CoA hydrolase could provide novel therapeutic approaches for osteoarthritis.
Neurological Disorders
In the brain, acetyl-CoA is essential for neurotransmitter synthesis, particularly acetylcholine. The regulatory effects of acetyl-CoA distribution in healthy and diseased brain have been reviewed, emphasizing the role of enzymes like acetyl-CoA hydrolase in maintaining acetyl-CoA homeostasis. Dysregulation of acetyl-CoA metabolism has been linked to neurodegenerative conditions such as Alzheimer's disease, where cholinergic deficits are prominent. Modulating acetyl-CoA hydrolase activity could potentially influence acetylcholine levels and cognitive function, though more research is needed.
From acetyl-CoA hydrolase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of acetyl-CoA hydrolase activity increase lipid accumulation? | CRISPR knockout of ACOT12 in HepG2 cells |
| Does a point mutation in the catalytic site abolish enzyme activity? | Knock-in of catalytic dead mutant in yeast ACH1 |
| Can overexpression of acetyl-CoA hydrolase reduce acetyl-CoA levels? | Overexpression of ACOT12 in hepatocytes |
| How does acetyl-CoA hydrolase activity affect cholesterol synthesis? | Knockout of ACOT1 in rat liver cells |
| What is the subcellular localization of acetyl-CoA hydrolase? | Tagged knock-in of ACH1 with GFP in yeast |
| Does acetyl-CoA hydrolase regulate YAP signaling? | ACOT12 knockout in mouse liver followed by YAP target analysis |
How to Study the acetyl-CoA hydrolase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| DTNB assay | Acetyl-CoA hydrolase activity | Enzyme kinetics and inhibitor screening |
| LC-MS metabolomics | Acetyl-CoA, acetate, CoA levels | Metabolic profiling in knockout cells |
| CRISPR knockout screen | Genes affecting acetyl-CoA homeostasis | Identifying synthetic lethal interactions |
| GFP tagging and microscopy | Subcellular localization | Determining organelle-specific functions |
| RNA-seq | Transcriptional changes upon enzyme modulation | Pathway analysis in disease models |
| Western blot | Protein expression levels | Validating knockout or overexpression |
| 13C tracing | Metabolic flux | Quantifying acetyl-CoA utilization |
| Co-immunoprecipitation | Protein-protein interactions | Identifying regulatory complexes |
Enzymatic Activity Assays
Acetyl-CoA hydrolase activity can be measured using spectrophotometric assays that monitor the release of CoA from acetyl-CoA. Typically, the thiol group of CoA reacts with DTNB (5,5'-dithiobis-(2-nitrobenzoic acid)) to produce a yellow color, which is quantified at 412 nm. This method is widely used to assess enzyme kinetics, substrate specificity, and inhibitor effects. In yeast, Ach1p activity has been characterized using such assays, revealing its role in acetate utilization.
Metabolomics and Flux Analysis
Metabolomic approaches, such as liquid chromatography-mass spectrometry (LC-MS), can quantify acetyl-CoA, acetate, and CoA levels in cells and tissues. By comparing wild-type and knockout models, researchers can determine the impact of acetyl-CoA hydrolase activity on metabolic flux. Stable isotope tracing with 13C-labeled substrates can further elucidate how acetyl-CoA is partitioned between oxidation and lipid synthesis.
CRISPR-Based Genetic Screens
CRISPR knockout screens can identify genes that regulate acetyl-CoA hydrolase activity or are synthetic lethal with its loss. For example, a genome-wide screen in cancer cells could reveal pathways that compensate for ACOT12 deficiency, highlighting potential therapeutic targets. Such screens are powerful for uncovering genetic interactions and regulatory networks.
Imaging and Subcellular Localization
Fluorescence microscopy of tagged acetyl-CoA hydrolase (e.g., GFP fusion) can reveal its subcellular localization and dynamics. In yeast, Ach1p-GFP has been used to show mitochondrial and cytosolic distribution. In mammalian cells, organelle-specific markers can be used to confirm localization. Live-cell imaging can also track changes in enzyme localization under metabolic stress.
How CRISPR Can Be Used to Study GO:0003986 acetyl-CoA hydrolase activity
Knockout
CRISPR knockout of genes encoding acetyl-CoA hydrolase activity, such as ACOT12 or ACH1, allows researchers to study loss-of-function phenotypes. For example, ACOT12 knockout in liver cells increases acetyl-CoA levels, promotes glycerolipid biosynthesis, and activates YAP signaling, demonstrating its tumor-suppressive role. In yeast, ACH1 deletion impairs growth on acetate, confirming its role in acetate utilization. Knockout models are essential for understanding the physiological consequences of reduced enzyme activity.
Point Mutation
Introducing point mutations in the catalytic residues of acetyl-CoA hydrolase can abolish enzymatic activity while preserving protein structure. This approach helps distinguish between catalytic and non-catalytic functions. For instance, mutating the catalytic serine in ACOT12 could clarify whether its tumor-suppressive effects depend on hydrolase activity. In yeast, catalytic mutants of Ach1p have been used to study its role in acetate metabolism.
Knock-in
Knock-in of tagged versions of acetyl-CoA hydrolase (e.g., GFP or FLAG) enables visualization and purification of the enzyme. This is useful for determining subcellular localization and identifying interacting proteins. For example, GFP knock-in of ACH1 in yeast revealed its mitochondrial and cytosolic distribution. In mammalian cells, knock-in of ACOT12 with a tag can facilitate proteomic studies.
Overexpression
Overexpression of acetyl-CoA hydrolase can reduce cellular acetyl-CoA levels and suppress lipid synthesis. In cancer cells, ACOT12 overexpression inhibits proliferation and tumor growth by limiting glycerolipid biosynthesis. Overexpression models are valuable for testing whether increased enzyme activity is sufficient to reverse disease phenotypes, such as hepatic steatosis.
How EDITGENE Supports acetyl-CoA hydrolase activity Research
Researchers studying acetyl-CoA hydrolase activity-related genes often need to determine whether a candidate gene is causally involved in metabolic regulation, disease progression, or drug response. EDITGENE provides comprehensive CRISPR-based services to accelerate this research, from gene knockout to precise point mutations and knock-in models.
Contact EDITGENE today to design your custom CRISPR model for acetyl-CoA hydrolase activity research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
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| ACOT8 Knockout HEK293 Cell Line | EDJ-KQ6860 | Human | 10005 | Details Get a Quote |
| ACAA2 Knockout HEK293 Cell Line | EDJ-KQ7051 | Human | 10449 | Details Get a Quote |
| ACOT9 Knockout HEK293 Cell Line | EDJ-KQ8085 | Human | 23597 | Details Get a Quote |
| ACOT12 Knockout HEK293 Cell Line | EDJ-KQ9343 | Human | 134526 | Details Get a Quote |
| ACOT9 Knockout A-549 Cell Line | EDJ-KQ33932 | Human | 23597 | Details Get a Quote |
| ACOT9 Knockout HeLa Cell Line | EDJ-KQ33933 | Human | 23597 | Details Get a Quote |
| ACAA2 Knockout HCT 116 Cell Line | EDJ-KQ30462 | Human | 10449 | Details Get a Quote |
| ACOT8 Knockout A-549 Cell Line | EDJ-KQ31434 | Human | 10005 | Details Get a Quote |
| ACOT8 Knockout HCT 116 Cell Line | EDJ-KQ31435 | Human | 10005 | Details Get a Quote |
| ACOT8 Knockout HeLa Cell Line | EDC08237 | Human | 10005 | Details Get a Quote |
| ACAA2 Knockout A-549 Cell Line | EDJ-KQ31836 | Human | 10449 | Details Get a Quote |
| ACAA2 Knockout HeLa Cell Line | EDJ-KQ31838 | Human | 10449 | Details Get a Quote |
| ACOT9 Knockout HCT 116 Cell Line | EDJ-KQ32594 | Human | 23597 | Details Get a Quote |
| ACOT12 Knockout HeLa Cell Line | EDJ-KQ58340 | Human | 134526 | Details Get a Quote |
| ACOT12 Knockout A-549 Cell Line | EDJ-KQ66829 | Human | 134526 | Details Get a Quote |
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Frequently Asked Questions About acetyl-CoA hydrolase activity
What is acetyl-CoA hydrolase activity?
Acetyl-CoA hydrolase activity (GO:0003986) is the enzymatic catalysis of the reaction: acetyl-CoA + H2O = acetate + CoA + H+. It regulates cellular acetyl-CoA levels.
What genes are involved in acetyl-CoA hydrolase activity?
Key genes include ACOT12, ACOT1, ACOT2, ACOT7, and ACH1 in yeast. These encode enzymes with acetyl-CoA hydrolase activity or related thioesterases.
How is acetyl-CoA hydrolase activity measured?
It is commonly measured using a DTNB-based spectrophotometric assay that detects CoA release, or by LC-MS metabolomics quantifying acetyl-CoA and acetate.
What diseases are associated with acetyl-CoA hydrolase activity?
Dysregulation is linked to non-alcoholic fatty liver disease, hepatocarcinogenesis, osteoarthritis, and neurological disorders.
What is the role of ACOT12 in cancer?
ACOT12 suppresses YAP-mediated hepatocarcinogenesis by limiting glycerolipid biosynthesis. Its downregulation increases acetyl-CoA and promotes tumor growth.
How does acetyl-CoA hydrolase affect cholesterol metabolism?
In rats, acetyl-CoA hydrolase activity correlates with cholesterol synthesis, influencing hepatic cholesterol levels.
Can CRISPR be used to study acetyl-CoA hydrolase activity?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models enable functional studies of genes like ACOT12 and ACH1.
What is the subcellular localization of acetyl-CoA hydrolase?
It is found in mitochondria and cytosol, depending on the organism and cell type.
Is acetyl-CoA hydrolase activity conserved across species?
Yes, from yeast to mammals. Yeast Ach1p is a well-studied homolog involved in acetate utilization.
What are potential therapeutic targets for acetyl-CoA hydrolase-related diseases?
Modulating ACOT12 activity or downstream lipid synthesis pathways could treat liver cancer and NAFLD.
Conclusion
Acetyl-CoA hydrolase activity (GO:0003986) is a fundamental enzymatic function that regulates acetyl-CoA homeostasis, impacting energy metabolism, lipid synthesis, and gene regulation. Its dysregulation is implicated in major diseases such as NAFLD, hepatocarcinogenesis, and osteoarthritis, making it a promising therapeutic target. Advances in CRISPR-based models and metabolomic techniques are accelerating our understanding of this enzyme's roles in health and disease. EDITGENE provides comprehensive services to support research on acetyl-CoA hydrolase activity, from gene knockout to high-throughput screening, empowering discoveries that could lead to novel treatments.
References
- 1. Wang S et al.. 2021. Hyperoside attenuates non-alcoholic fatty liver disease in rats via cholesterol metabolism and bile acid metabolism.. J Adv Res 34:109-122 PMID: 35024184
- 2. Ebisuno S et al.. 1988. Acetyl-CoA hydrolase: relation between activity and cholesterol metabolism in rat.. Am J Physiol 255(5 Pt 2):R724-30 PMID: 2903683
- 3. He H et al.. 2023. Acyl-CoA thioesterase 12 suppresses YAP-mediated hepatocarcinogenesis by limiting glycerolipid biosynthesis.. Cancer Lett 565:216210 PMID: 37150501
- 4. Han S. 2022. Osteoarthritis year in review 2022: biology.. Osteoarthritis Cartilage 30(12):1575-1582 PMID: 36150676
- 5. de Mata ZS et al.. 1997. Acetyl-CoA hydrolase activity and function in Ascaris suum muscle mitochondria.. Comp Biochem Physiol B Biochem Mol Biol 116(3):379-83 PMID: 9114498
- 6. Buu LM et al.. 2003. Functional characterization and localization of acetyl-CoA hydrolase, Ach1p, in Saccharomyces cerevisiae.. J Biol Chem 278(19):17203-9 PMID: 12606555
- 7. Lee FJ et al.. 1996. Acetyl-CoA hydrolase involved in acetate utilization in Saccharomyces cerevisiae.. Biochim Biophys Acta 1297(1):105-9 PMID: 8841387
- 8. Ronowska A et al.. 2018. The Regulatory Effects of Acetyl-CoA Distribution in the Healthy and Diseased Brain.. Front Cell Neurosci 12:169 PMID: 30050410
