ACOT7 Human
Description
Primary Characteristics
ACOT7 Human is a recombinant protein expressed in Escherichia coli and consists of:
Functional Role in Fatty Acid Metabolism
ACOT7 hydrolyzes long-chain acyl-CoA thioesters (C8–C18) into free fatty acids (FFAs) and coenzyme A (CoA), modulating lipid homeostasis . Key functions include:
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Neuronal protection: Prevents lipid overload by evicting FFAs from neurons, which are then metabolized by astrocytes .
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Energy regulation: Maintains ATP levels by modulating acyl-CoA/CoA ratios, critical for myelin maintenance .
Alzheimer’s Disease (AD)
ACOT7 has emerged as a promising serum biomarker for AD:
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Diagnostic performance:
| Biomarker | AUC (95% CI) | Sensitivity (95% CI) | Specificity (95% CI) | Source |
|---|---|---|---|---|
| ACOT7 | 0.83 (0.80–0.86) | 80% (75–84%) | 74% (69–79%) | |
| Aβ42/40 ratio | 0.70 | 69% | 76% |
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Pathological mechanisms:
Oncological Implications
ACOT7 acts as an oncogene in lung adenocarcinoma (LUAD):
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Tumor microenvironment: Promotes cisplatin resistance and ferroptosis suppression via ACOT7-regulated pathways .
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Expression patterns:
Research Tools
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Recombinant protein: Used in enzymatic assays, cell culture models (e.g., SK-N-SH APPwt cells), and Western blotting .
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Knockdown studies: siRNA-mediated suppression reduces ACOT7 expression by ~88%, altering Aβ42 and BACE1 levels .
Therapeutic Potential
Product Specs
Q&A
What is ACOT7’s primary biological function in human cells?
ACOT7 (acyl-CoA thioesterase 7) catalyzes the hydrolysis of arachidonoyl-CoA to arachidonic acid, a precursor for pro-inflammatory eicosanoids like prostaglandins. This enzyme regulates lipid metabolism, cell proliferation, and glucose utilization, with expression highest in brain, testis, and pituitary tissues . In cancer contexts, ACOT7 overexpression correlates with enhanced tumor growth and metabolic reprogramming, particularly in lung adenocarcinoma (LUAD) .
Key Experimental Models:
How is ACOT7 implicated in cancer progression?
ACOT7 acts as an oncogene in multiple cancers, including LUAD, by promoting cell cycle progression and glucose metabolism. Pan-cancer analysis revealed:
What methodologies are used to analyze ACOT7’s role in the tumor microenvironment?
ACOT7’s immune microenvironment interactions are investigated via:
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Gene Set Enrichment Analysis (GSEA): Identifies pathways linked to immune cell infiltration (e.g., T-cell activation) .
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CIBERSORT: Quantifies immune cell subpopulations (e.g., macrophages, CD8+ T cells) in ACOT7-high/low tumors .
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Correlation with Immune Markers: ACOT7 expression associates with tumor mutational burden (TMB) and microsatellite instability (MSI) status .
Table 1: ACOT7-Immune Microenvironment Correlations
How do researchers address contradictions in ACOT7 expression across cancers?
ACOT7 exhibits heterogeneous expression:
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Upregulated in BLCA, BRCA, LUAD; downregulated in KICH/KIRP .
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Mechanistic Insights:
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Functional validation: siRNA knockdown in LUAD models (e.g., PC9 cells) confirms context-specific oncogenic roles .
What statistical approaches optimize ACOT7 prognostic nomogram development?
Nomogram construction for LUAD prognosis involves:
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Multivariate Cox Regression: Identifies ACOT7 and clinical variables (e.g., TNM stage) as predictors .
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Variance Inflation Factor (VIF): Ensures low multicollinearity (VIF <5) between variables .
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Calibration/Validation:
Example Workflow:
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Data preprocessing (log₂ transformation, outlier removal).
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Feature selection (LASSO regression).
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Nomogram visualization (R “rms” package).
How does ACOT7 modulate drug responses in cancer therapy?
ACOT7 expression correlates with sensitivity to tyrosine kinase inhibitors (TKIs):
Methodology:
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GDSC database: Spearman’s correlation between ACOT7 mRNA levels and drug IC50 values .
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In vitro validation: siRNA-mediated ACOT7 knockdown in LUAD cells to assess drug synergy .
What technical limitations exist in ACOT7 gene expression analysis?
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Tissue Heterogeneity: Bulk RNA-seq data may mask cell-type-specific ACOT7 expression (e.g., stromal vs. tumor cells) .
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Epigenetic Interference: Promoter methylation and post-transcriptional regulation complicate expression-phenotype correlations .
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Model Systems: 2D cell cultures may inadequately replicate 3D tumor microenvironments .
How can researchers improve ACOT7-targeted therapeutic strategies?
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Combination Therapies: Pair ACOT7 inhibitors with immunotherapies (e.g., PD-1 blockers) to exploit immune microenvironment interactions .
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Biomarker-Guided Trials: Use ACOT7 expression levels to stratify patients for TKI therapy (e.g., afatinib) .
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CRISPR Screening: Identify synthetic lethal partners of ACOT7 in LUAD models .
What unanswered questions persist in ACOT7 research?
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Metabolic Crosstalk: Role of ACOT7 in lipid/glucose metabolism reprogramming.
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Splice Variants: Functional differences between ACOT7 isoforms in cancer.
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Liquid Biopsy Markers: Circulating ACOT7 or metabolites as non-invasive biomarkers.
Product Science Overview
The ACOT7 gene is located on chromosome 1 at the band 1p36.31 and spans approximately 130,000 base pairs . The gene encodes multiple isoforms through alternative splicing, which results in distinct proteins with different subcellular localizations . The primary structure of ACOT7 includes a catalytic domain responsible for its hydrolase activity, which is essential for breaking down fatty acyl-CoA esters into free fatty acids and Coenzyme A (CoASH) .
ACOT7 is involved in various biological processes, including:
- Fatty Acid Metabolism: ACOT7 hydrolyzes long-chain fatty acyl-CoA esters, which are crucial intermediates in lipid metabolism . This activity helps regulate the balance between free fatty acids and acyl-CoA esters within cells.
- Energy Production: By participating in the β-oxidation pathway, ACOT7 contributes to the degradation of fatty acids, providing energy through the citric acid cycle .
- Lipid Biosynthesis: The enzyme’s activity is also linked to lipid biosynthesis, ensuring the availability of free fatty acids for the synthesis of complex lipids .
ACOT7 is ubiquitously expressed in various tissues, with high expression levels in the brain, particularly in regions such as the thalamus, prefrontal cortex, and hippocampus . The enzyme is found in multiple subcellular locations, including the cytosol, mitochondria, and peroxisomes . Its presence in these organelles suggests a role in both energy production and lipid metabolism.
Altered expression of ACOT7 has been associated with certain medical conditions. For instance, decreased expression of ACOT7 may be linked to mesial temporal lobe epilepsy, a neurological disorder characterized by recurrent seizures originating from the temporal lobe of the brain . Additionally, the enzyme’s role in lipid metabolism and energy production makes it a potential target for therapeutic interventions in metabolic disorders .
Human recombinant ACOT7 is used in research to study its enzymatic properties, regulatory mechanisms, and potential therapeutic applications. Recombinant proteins are produced through genetic engineering techniques, allowing scientists to investigate the enzyme’s structure-function relationships and its role in various biological processes .
