GO:0120523 medium-chain fatty acyl-CoA oxidase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0120523 describes the molecular function that catalyzes the reaction: a medium-chain 2,3-saturated fatty acyl-CoA + O2 = a medium-chain (2E)-enoyl-CoA + H2O2.
• This activity is a peroxisomal or mitochondrial enzyme function that introduces a double bond into medium-chain fatty acyl-CoAs, producing H2O2 and feeding into fatty acid beta-oxidation.
• In plants, medium-chain acyl-CoA oxidase activity is essential for embryo development and seed germination, as mutants accumulate acyl-CoAs and fail to develop.
• In mammals, medium-chain acyl-CoA dehydrogenase can acquire oxidase activity through specific mutations, such as Tyr375 to Lys375, linking this activity to inherited metabolic disorders.
• The enzyme mechanism involves FAD-dependent dehydrogenation and electron transfer to O2, with the oxidase side reaction modulated by substrate chain length and active-site residues.
• Research on GO:0120523 uses knockout, point-mutation, and overexpression models in Arabidopsis and mammalian cells to dissect its role in fatty acid metabolism and disease.
Description
Medium-chain fatty acyl-CoA oxidase activity (GO:0120523) is a molecular function that catalyzes the oxidation of medium-chain 2,3-saturated fatty acyl-CoA substrates to their corresponding (2E)-enoyl-CoA products, with concomitant reduction of oxygen to hydrogen peroxide. This reaction is a key step in the beta-oxidation of fatty acids, particularly in peroxisomes, where it initiates the breakdown of medium-chain fatty acids that cannot be handled efficiently by mitochondrial beta-oxidation. The activity is distinguished from medium-chain acyl-CoA dehydrogenase activity by its direct use of O2 as an electron acceptor, producing H2O2 rather than transferring electrons to the respiratory chain. Researchers study GO:0120523 because it sits at the intersection of lipid metabolism, oxidative stress, and inherited metabolic disease. In plants, mutations that abolish medium-chain acyl-CoA oxidase activity cause embryonic lethality and accumulation of acyl-CoA intermediates, demonstrating an essential role in development. In mammals, the related medium-chain acyl-CoA dehydrogenase can be engineered to acquire oxidase activity, and naturally occurring mutations in this enzyme cause medium-chain acyl-CoA dehydrogenase deficiency, a disorder of fatty acid oxidation. Understanding the molecular details of this activity therefore informs both basic enzymology and clinical genetics. The term is also relevant to metabolic engineering and drug discovery, as modulating fatty acid oxidation can influence energy homeostasis, inflammation, and cell survival. This article synthesizes the QuickGO definition and verified literature to provide a research-grade overview of GO:0120523, covering its mechanism, key genes, disease links, and experimental models.
medium-chain fatty acyl-CoA oxidase activity At A Glance
| GO ID | GO:0120523 |
|---|---|
| GO term | medium-chain fatty acyl-CoA oxidase activity |
| Ontology | molecular_function |
| Synonym | none |
| Definition | Catalysis of the reaction: a medium-chain 2,3-saturated fatty acyl-CoA + O2 = a medium-chain (2E)-enoyl-CoA + H2O2. |
| Major function | Oxidation of medium-chain fatty acyl-CoAs to enoyl-CoAs with production of H2O2, contributing to fatty acid beta-oxidation. |
| Cofactor | FAD (flavin adenine dinucleotide) |
| Subcellular location | Peroxisome (plant and mammalian medium-chain acyl-CoA oxidases) and mitochondria (related acyl-CoA dehydrogenases) |
| Related activity | Medium-chain acyl-CoA dehydrogenase activity (EC 1.3.8.-) |
What Is GO:0120523?
GO:0120523 medium-chain fatty acyl-CoA oxidase activity is defined as the catalysis of the reaction: a medium-chain 2,3-saturated fatty acyl-CoA + O2 = a medium-chain (2E)-enoyl-CoA + H2O2. In other words, it is an oxidoreductase activity that uses molecular oxygen to dehydrogenate a medium-chain fatty acyl-CoA, introducing a trans double bond at the 2,3-position and releasing hydrogen peroxide. This activity is part of the fatty acid beta-oxidation pathway and is typically associated with peroxisomal or mitochondrial enzymes that contain FAD as a cofactor.
Why Is medium-chain fatty acyl-CoA oxidase activity Important in Cell Biology?
GO:0120523 is important because it represents a critical enzymatic step in fatty acid catabolism that directly links lipid breakdown to reactive oxygen species production. In plants, this activity is indispensable for embryo development and seed germination, as loss-of-function mutants accumulate medium-chain acyl-CoAs and arrest early in development. In mammals, the related medium-chain acyl-CoA dehydrogenase can acquire oxidase activity through mutation, and defects in this enzyme cause medium-chain acyl-CoA dehydrogenase deficiency, a disease characterized by hypoketotic hypoglycemia and fatty acid accumulation. Moreover, the oxidase activity of acyl-CoA dehydrogenases contributes to oxidative stress and has been implicated in metabolic inflammation and obesity-related pathologies. Thus, understanding GO:0120523 informs developmental biology, metabolic disease, and redox biology.
• Essential for plant embryo development and seed germination, as mutants in medium-chain acyl-CoA oxidase activity are lethal or fail to germinate.
• Provides a route for peroxisomal beta-oxidation of medium-chain fatty acids that cannot be efficiently oxidized in mitochondria.
• Generates H2O2, which can act as a signaling molecule or contribute to oxidative stress.
• Mutations in medium-chain acyl-CoA dehydrogenase can confer oxidase activity, linking this function to inherited metabolic disorders.
• Modulates fatty acid-induced inflammation in macrophages, with implications for obesity and metabolic syndrome.
• Serves as a target for understanding enzyme mechanism and substrate specificity in the acyl-CoA oxidase/dehydrogenase family.
• Relevant to metabolic engineering of oilseed crops and biofuel production through altered fatty acid composition.
• Potential biomarker or therapeutic target in disorders of fatty acid oxidation and redox imbalance.
What Happens During medium-chain fatty acyl-CoA oxidase activity?
Substrate binding and FAD reduction
In simple terms: The enzyme grabs a medium-chain fatty acyl-CoA and pulls electrons off it using a built-in FAD molecule.
The reaction begins with the binding of a medium-chain 2,3-saturated fatty acyl-CoA to the enzyme active site. The enzyme contains a non-covalently bound FAD cofactor that accepts electrons from the substrate, reducing FAD to FADH2 and forming a trans-2-enoyl-CoA product. This step is analogous to the dehydrogenation catalyzed by medium-chain acyl-CoA dehydrogenase, but the oxidase activity directly transfers electrons to molecular oxygen rather than to the respiratory chain.
Oxygen reduction and H2O2 production
In simple terms: Instead of passing electrons to the respiratory chain, the enzyme hands them to oxygen, making hydrogen peroxide.
In the oxidase reaction, the reduced FADH2 reacts with molecular oxygen (O2) to form hydrogen peroxide (H2O2) and regenerate the oxidized FAD. This direct electron transfer to O2 distinguishes the oxidase activity from dehydrogenase activity and produces a reactive oxygen species that can influence cellular redox balance. The efficiency of this step is influenced by the enzyme's active-site environment and substrate chain length.
Product release and beta-oxidation continuation
In simple terms: The enoyl-CoA product is released and enters the next steps of fatty acid breakdown.
After formation, the medium-chain (2E)-enoyl-CoA product is released from the active site and can be further processed by the beta-oxidation pathway, including hydratation and thiolytic cleavage. In peroxisomes, this allows medium-chain fatty acids to be shortened for eventual mitochondrial oxidation or other metabolic fates. In plants, the continuation of beta-oxidation is essential for seedling establishment, as mutants unable to perform this step accumulate acyl-CoAs and fail to develop.
Regulation by substrate chain length and active-site residues
In simple terms: The enzyme prefers certain fatty acid lengths, and specific amino acids in the active site control its activity.
The oxidase activity is highly dependent on the chain length of the acyl-CoA substrate, with medium-chain substrates (typically C6-C12) being preferred. Mutational studies have shown that specific active-site residues, such as Tyr375 in medium-chain acyl-CoA dehydrogenase, can be mutated to Lys375 to switch the enzyme from dehydrogenase to oxidase activity, highlighting the structural basis for oxygen reactivity. Additionally, the dissociation of the enzyme-product complex can limit turnover, as seen with octenoyl-CoA in medium-chain acyl-CoA dehydrogenase.
Cellular context and metabolic integration
In simple terms: This activity happens in specific cell compartments and connects to wider metabolism.
In plants, medium-chain acyl-CoA oxidase activity is localized to peroxisomes and is transcriptionally induced during seed germination, as shown by promoter trapping of a novel medium-chain acyl-CoA oxidase. In mammals, related oxidase activities can occur in mitochondria and peroxisomes, and the balance between dehydrogenase and oxidase activities can influence energy production and oxidative stress. The activity is integrated with other metabolic pathways, including ketogenesis and inflammation, as evidenced by the role of fatty acid oxidation in macrophage metaflammation.
Key Genes Involved in GO:0120523 medium-chain fatty acyl-CoA oxidase activity
The following genes and proteins are directly or functionally linked to medium-chain fatty acyl-CoA oxidase activity (GO:0120523) based on the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ACOX1 | Peroxisomal acyl-CoA oxidase that catalyzes the first step of beta-oxidation, including medium-chain substrates | Mutations cause peroxisomal disorders; model for studying oxidase activity |
| ACADM | Medium-chain acyl-CoA dehydrogenase; can acquire oxidase activity upon mutation | Deficiency causes MCAD deficiency; Tyr375 mutation switches to oxidase |
| ACOX2 | Peroxisomal acyl-CoA oxidase involved in branched-chain fatty acid oxidation | Related to medium-chain oxidase activity; potential redundancy |
| ACOX3 | Peroxisomal acyl-CoA oxidase in plants and mammals | Contributes to medium-chain acyl-CoA oxidation in seeds |
| BNIP3 | Mitophagy receptor that regulates macrophage fatty acid oxidation and inflammation | Links fatty acid oxidation to obesity-induced metaflammation |
| ETFA | Electron transfer flavoprotein subunit alpha, accepts electrons from acyl-CoA dehydrogenases | Relevant to dehydrogenase vs oxidase electron transfer |
| ETFB | Electron transfer flavoprotein subunit beta | Part of electron transfer chain for acyl-CoA dehydrogenases |
| HADHA | Trifunctional protein subunit alpha, involved in mitochondrial beta-oxidation | Downstream of medium-chain acyl-CoA oxidation |
| CPT1A | Carnitine palmitoyltransferase 1A, regulates fatty acid entry into mitochondria | Context for medium-chain fatty acid metabolism |
| PPARA | Peroxisome proliferator-activated receptor alpha, regulates fatty acid oxidation genes | Transcriptional regulator of ACOX genes |
| NR1H3 | Liver X receptor alpha, regulates lipid metabolism | Potential regulator of medium-chain acyl-CoA oxidase expression |
| SLC25A20 | Carnitine-acylcarnitine translocase, transports fatty acylcarnitines | Related to fatty acid oxidation disorders |
| ACADVL | Very-long-chain acyl-CoA dehydrogenase | Comparative enzyme for chain-length specificity |
| ACADS | Short-chain acyl-CoA dehydrogenase | Comparative enzyme for oxidase activity |
| ACADL | Long-chain acyl-CoA dehydrogenase | Comparative enzyme for substrate specificity |
| DECR1 | 2,4-dienoyl-CoA reductase, auxiliary beta-oxidation enzyme | Downstream of enoyl-CoA products |
| EHHADH | Enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase | Peroxisomal beta-oxidation multifunctional enzyme |
| SCP2 | Sterol carrier protein 2, involved in peroxisomal lipid metabolism | Potential interactor in medium-chain oxidation |
How Is medium-chain fatty acyl-CoA oxidase activity Regulated?
The expression and activity of medium-chain fatty acyl-CoA oxidase are regulated at multiple levels. In plants, the promoter of a medium-chain acyl-CoA oxidase gene is induced transcriptionally during seed germination, linking activity to developmental cues. In mammals, peroxisome proliferator-activated receptor alpha (PPARA) and other nuclear receptors regulate the expression of ACOX genes in response to fatty acid levels and metabolic state. At the protein level, the oxidase activity can be modulated by substrate availability, FAD cofactor binding, and post-translational modifications, although specific modifications remain to be fully defined. Additionally, the balance between dehydrogenase and oxidase activities of related enzymes can be shifted by mutations, as shown for medium-chain acyl-CoA dehydrogenase. In macrophages, BNIP3-mediated mitophagy influences fatty acid oxidation and inflammation, indirectly affecting medium-chain acyl-CoA oxidase activity.
medium-chain fatty acyl-CoA oxidase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ACADM | Medium-chain acyl-CoA dehydrogenase deficiency; mutation Tyr375Lys confers oxidase activity | Knockout and point-mutation (Y375K) knock-in mice or cell lines |
| ACOX1 | Peroxisomal beta-oxidation defects; plant embryo lethality | Arabidopsis acox1 mutants; human ACOX1 knockout cells |
| BNIP3 | Obesity-induced adipose tissue metaflammation | Macrophage-specific Bnip3 knockout mice |
| ACOX3 | Seed germination and peroxisomal fatty acid oxidation | Arabidopsis acox3 promoter-trapped lines |
| ETFA | Glutaric acidemia type II; electron transfer flavoprotein deficiency | Patient-derived fibroblasts; ETFA knockout models |
Medium-chain acyl-CoA dehydrogenase deficiency
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an inherited metabolic disorder caused by mutations in the ACADM gene. While MCAD primarily functions as a dehydrogenase, mutations such as Tyr375 to Lys375 can confer oxidase activity, altering the enzyme's catalytic properties. Clinically, MCAD deficiency presents with hypoketotic hypoglycemia, vomiting, and lethargy during fasting, and can lead to sudden death if untreated. The accumulation of medium-chain acyl-CoAs and acylcarnitines is a hallmark, and assays for acyl-CoA dehydrogenase activity in muscle biopsies are used for diagnosis. Understanding the oxidase side reaction may provide insights into disease mechanisms and potential therapies.
Peroxisomal disorders and fatty acid oxidation defects
Defects in peroxisomal beta-oxidation, including medium-chain acyl-CoA oxidase activity, are associated with peroxisomal disorders such as X-linked adrenoleukodystrophy and Zellweger spectrum disorders. In plants, mutants lacking medium-chain acyl-CoA oxidase activity accumulate acyl-CoAs and fail to develop embryos, demonstrating the essential role of this activity in development. In humans, impaired peroxisomal fatty acid oxidation leads to accumulation of very-long-chain fatty acids and neurological dysfunction. Although direct mutations in medium-chain acyl-CoA oxidase genes are rare, the pathway is critical for lipid homeostasis and redox balance.
Obesity, inflammation, and metabolic syndrome
Fatty acid oxidation in macrophages is linked to obesity-induced adipose tissue metaflammation. BNIP3-mediated mitophagy regulates macrophage fatty acid oxidation, and dysregulation of this process contributes to chronic inflammation and insulin resistance. Medium-chain fatty acyl-CoA oxidase activity, by producing H2O2 and influencing redox signaling, may modulate inflammatory responses. Additionally, the bioactivation of cytotoxic 4-thiaalkanoic acids by medium-chain acyl-CoA dehydrogenase involves elimination reactions that could intersect with oxidase chemistry. Thus, this activity is relevant to metabolic syndrome and related inflammatory conditions.
Cancer and oxidative stress
Altered fatty acid oxidation is a metabolic hallmark of cancer, supporting energy production and redox homeostasis. The oxidase activity of acyl-CoA dehydrogenases generates H2O2, which can contribute to oxidative stress and DNA damage, potentially promoting tumorigenesis or sensitizing cells to therapy. In some cancers, upregulation of fatty acid oxidation enzymes, including acyl-CoA oxidases, supports proliferation under metabolic stress. Targeting medium-chain fatty acyl-CoA oxidase activity may therefore be a strategy to disrupt cancer metabolism, although direct evidence in human tumors remains limited.
From medium-chain fatty acyl-CoA oxidase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of medium-chain acyl-CoA oxidase activity cause developmental arrest? | Knockout of ACOX genes in Arabidopsis or mouse embryos |
| Can a point mutation switch dehydrogenase to oxidase activity? | ACADM Y375K point-mutation knock-in in cell lines or mice |
| What is the subcellular localization of medium-chain acyl-CoA oxidase? | Tagged knock-in of ACOX1 with fluorescent protein in mammalian cells |
| Does overexpression of medium-chain acyl-CoA oxidase alter lipid metabolism? | Overexpression of ACOX1 or ACADM in hepatocytes or adipocytes |
| How does BNIP3-mediated mitophagy affect fatty acid oxidation? | BNIP3 knockout macrophages and obesity models |
| What is the role of medium-chain acyl-CoA oxidase in seed germination? | Promoter trapping and inducible expression in Arabidopsis |
How to Study the medium-chain fatty acyl-CoA oxidase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Spectrophotometric oxidase assay | H2O2 production or enoyl-CoA formation | Enzyme kinetics and inhibitor testing |
| Acyl-CoA dehydrogenase activity assay | Dehydrogenase vs oxidase activity in muscle biopsies | Diagnosis of MCAD deficiency |
| CRISPR-Cas9 knockout | Loss of gene function | Studying developmental and metabolic roles |
| Point-mutation knock-in | Specific amino acid substitution (e.g., Y375K) | Switching dehydrogenase to oxidase activity |
| Metabolomics/lipidomics | Acyl-CoA and acylcarnitine levels | Detecting pathway defects and flux |
| Fluorescence microscopy | Subcellular localization of tagged enzyme | Determining peroxisomal vs mitochondrial targeting |
| Promoter trapping/reporter assays | Transcriptional regulation | Identifying developmental and tissue-specific expression |
| H2O2 biosensors | Real-time oxidative stress | Linking oxidase activity to redox signaling |
Enzymatic activity assays
Direct measurement of medium-chain fatty acyl-CoA oxidase activity is performed using spectrophotometric or fluorometric assays that monitor the production of H2O2 or the formation of enoyl-CoA. For example, acyl-CoA dehydrogenase activity in muscle biopsies can be assayed to diagnose MCAD deficiency, and similar methods can be adapted for oxidase activity. These assays typically use medium-chain acyl-CoA substrates and electron acceptors such as dichlorophenolindophenol or oxygen electrodes.
Genetic and molecular biology approaches
Knockout, point-mutation, and overexpression models are essential for studying GO:0120523. In Arabidopsis, T-DNA insertion mutants in medium-chain acyl-CoA oxidase genes have been used to demonstrate embryonic lethality and acyl-CoA accumulation. In mammalian cells, CRISPR-Cas9 can generate ACADM Y375K knock-in to study the switch from dehydrogenase to oxidase activity. Promoter trapping and transcriptional reporters reveal developmental regulation of medium-chain acyl-CoA oxidase genes.
Metabolomics and lipidomics
Mass spectrometry-based metabolomics and lipidomics quantify acyl-CoA species and acylcarnitines, providing readouts of medium-chain fatty acyl-CoA oxidase activity in cells and tissues. In plant mutants, accumulation of medium-chain acyl-CoAs is a hallmark of defective beta-oxidation. In mammalian systems, acylcarnitine profiling is used clinically to diagnose fatty acid oxidation disorders, including MCAD deficiency. These methods can be combined with stable isotope tracing to follow flux through the oxidase step.
Imaging and subcellular localization
Fluorescence microscopy of tagged medium-chain acyl-CoA oxidase (e.g., GFP fusion) reveals peroxisomal or mitochondrial localization. In plants, promoter trapping of a novel medium-chain acyl-CoA oxidase showed expression during seed germination. In mammalian cells, co-localization with peroxisomal markers (e.g., PEX14) or mitochondrial markers (e.g., TOMM20) confirms compartmentalization. Live-cell imaging can also monitor H2O2 production using genetically encoded sensors.
How CRISPR Can Be Used to Study GO:0120523 medium-chain fatty acyl-CoA oxidase activity
Knockout
CRISPR-Cas9 knockout of medium-chain acyl-CoA oxidase genes (e.g., ACOX1, ACOX3) in cell lines or model organisms abolishes enzymatic activity, allowing researchers to study loss-of-function phenotypes such as acyl-CoA accumulation, developmental arrest, and altered lipid metabolism. In Arabidopsis, knockout mutants have demonstrated the essential role of medium-chain acyl-CoA oxidase in embryo development and seed germination. In mammalian cells, ACOX1 knockout can reveal compensatory pathways and sensitivity to fatty acid stress.
Point Mutation
Point-mutation knock-in using CRISPR-Cas9 can introduce specific amino acid changes that alter catalytic activity. For example, the ACADM Y375K mutation switches medium-chain acyl-CoA dehydrogenase to an oxidase, providing a model to study the structural basis of oxygen reactivity and its physiological consequences. Such models are valuable for dissecting the contribution of oxidase activity to disease phenotypes and for testing small-molecule modulators.
Knock-in
Tagged knock-in of medium-chain acyl-CoA oxidase genes with fluorescent or affinity tags (e.g., GFP, HA) enables real-time visualization and purification of the enzyme. This approach can confirm subcellular localization, as shown for plant medium-chain acyl-CoA oxidase during seed germination. In mammalian cells, knock-in of tags into endogenous ACOX1 or ACADM loci allows study of endogenous expression and interaction partners without overexpression artifacts.
Overexpression
CRISPR activation (CRISPRa) or lentiviral overexpression of medium-chain acyl-CoA oxidase genes can increase enzymatic activity, leading to elevated H2O2 production and altered fatty acid oxidation. Overexpression models are useful for studying the consequences of enhanced oxidase activity on cellular redox balance, inflammation, and metabolic flux. In plants, overexpression of medium-chain acyl-CoA oxidase can affect seed oil composition and germination efficiency.
How EDITGENE Supports medium-chain fatty acyl-CoA oxidase activity Research
Researchers studying medium-chain fatty acyl-CoA oxidase activity-related genes often need to determine whether a candidate gene is causally involved in fatty acid oxidation, redox signaling, or developmental processes. EDITGENE provides a comprehensive suite of CRISPR-based services to generate precisely engineered cell and animal models, enabling rigorous functional studies of GO:0120523 and its associated pathways.
Contact EDITGENE today to design your custom CRISPR model for medium-chain fatty acyl-CoA oxidase activity research.
Frequently Asked Questions About medium-chain fatty acyl-CoA oxidase activity
What is medium-chain fatty acyl-CoA oxidase activity?
It is a molecular function (GO:0120523) that catalyzes the reaction: a medium-chain 2,3-saturated fatty acyl-CoA + O2 = a medium-chain (2E)-enoyl-CoA + H2O2, as defined by QuickGO.
What genes are involved in medium-chain fatty acyl-CoA oxidase activity?
Key genes include ACOX1, ACOX3, and ACADM, which encode enzymes that can catalyze or be engineered to catalyze this activity.
What is the role of medium-chain acyl-CoA oxidase in plants?
In plants, it is essential for embryo development and seed germination; mutants accumulate acyl-CoAs and fail to develop.
How is medium-chain fatty acyl-CoA oxidase activity measured?
It can be measured using spectrophotometric assays that monitor H2O2 production or enoyl-CoA formation, as well as acyl-CoA dehydrogenase activity assays in muscle biopsies.
What diseases are associated with medium-chain acyl-CoA oxidase activity?
Defects in related enzymes cause medium-chain acyl-CoA dehydrogenase deficiency and peroxisomal disorders; altered activity is linked to obesity-induced inflammation.
Can medium-chain acyl-CoA dehydrogenase acquire oxidase activity?
Yes, mutation of Tyr375 to Lys375 in medium-chain acyl-CoA dehydrogenase allows it to acquire acyl-CoA oxidase activity.
What is the difference between acyl-CoA oxidase and acyl-CoA dehydrogenase?
Acyl-CoA oxidase transfers electrons directly to O2 to produce H2O2, while dehydrogenase transfers electrons to the respiratory chain via electron transfer flavoprotein.
Which model organisms are used to study medium-chain fatty acyl-CoA oxidase activity?
Arabidopsis thaliana is a key model for plant medium-chain acyl-CoA oxidase, while mammalian cell lines and mice are used for ACADM and ACOX1 studies.
How does BNIP3 relate to medium-chain fatty acyl-CoA oxidase activity?
BNIP3-mediated mitophagy regulates macrophage fatty acid oxidation and inflammation, indirectly influencing medium-chain acyl-CoA oxidase activity.
What CRISPR models are available for studying medium-chain fatty acyl-CoA oxidase activity?
Knockout, point-mutation knock-in (e.g., ACADM Y375K), tagged knock-in, and overexpression models can be generated in various cell types.
Conclusion
Medium-chain fatty acyl-CoA oxidase activity (GO:0120523) is a fundamental enzymatic function in fatty acid beta-oxidation, with critical roles in plant development, mammalian metabolism, and disease. The reaction produces H2O2 and enoyl-CoA products, linking lipid catabolism to redox signaling and energy homeostasis. Mutations that alter this activity, such as ACADM Y375K, provide insights into enzyme mechanism and inherited metabolic disorders. Research on GO:0120523 benefits from CRISPR-based models, including knockout, point-mutation, and overexpression systems, which enable precise dissection of its physiological functions. EDITGENE offers comprehensive services to generate these models and support mechanistic studies, helping researchers translate basic findings into therapeutic strategies for metabolic and inflammatory diseases.
References
- 1. Kim S et al.. 2025. BNIP3-mediated mitophagy in macrophages regulates obesity-induced adipose tissue metaflammation.. Autophagy 21(9):2009-2027 PMID: 40195021
- 2. Zeng J et al.. 2007. Mutation of Tyr375 to Lys375 allows medium-chain acyl-CoA dehydrogenase to acquire acyl-CoA oxidase activity.. Biochim Biophys Acta 1774(12):1628-34 PMID: 18061544
- 3. Rylott EL et al.. 2003. Arabidopsis mutants in short- and medium-chain acyl-CoA oxidase activities accumulate acyl-CoAs and reveal that fatty acid beta-oxidation is essential for embryo development.. J Biol Chem 278(24):21370-7 PMID: 12682048
- 4. DuPlessis ER et al.. 1998. Oxidase activity of the acyl-CoA dehydrogenases.. Biochemistry 37(29):10469-77 PMID: 9671517
- 5. Kumar NR et al.. 1995. Facile and restricted pathways for the dissociation of octenoyl-CoA from the medium-chain fatty acyl-CoA dehydrogenase (MCAD)-FADH2-octenoyl-CoA charge-transfer complex: energetics and mechanism of suppression of the enzyme's oxidase activity.. Biochemistry 34(29):9434-43 PMID: 7626613
- 6. Baker-Malcolm JF et al.. 1998. Elimination reactions in the medium-chain acyl-CoA dehydrogenase: bioactivation of cytotoxic 4-thiaalkanoic acids.. Biochemistry 37(5):1383-93 PMID: 9477967
- 7. Verity MA et al.. 1993. Assay of acyl-CoA dehydrogenase activity in frozen muscle biopsies: application to medium-chain acyl-CoA dehydrogenase deficiency.. Biochem Med Metab Biol 49(3):351-62 PMID: 8347379
- 8. Eastmond PJ et al.. 2000. Promoter trapping of a novel medium-chain acyl-CoA oxidase, which is induced transcriptionally during Arabidopsis seed germination.. J Biol Chem 275(44):34375-81 PMID: 10918060
