GO:0016624 oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0016624 describes a redox reaction in which an aldehyde or ketone (oxo) group is the electron donor and a disulfide bond is the electron acceptor.
• The term is defined in QuickGO as catalysis of an oxidation-reduction reaction in which an aldehyde or oxo group acts as a hydrogen or electron donor and reduces a disulfide.
• Enzymes with this activity include selenium-dependent oxidoreductases and polyamine oxidases that use disulfide chemistry to drive substrate oxidation [1,5].
• Dysregulation of these enzymes is linked to cancer, renal failure, and metabolic stress through altered polyamine and redox homeostasis [3,5,8].
• CRISPR knockout, point-mutation, knock-in, and overexpression models are essential to separate catalytic from non-catalytic functions of these enzymes.
• EDITGENE provides end-to-end CRISPR cell model and library screening services to study GO:0016624-related genes in disease-relevant contexts.
Description
GO:0016624, oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor, is a molecular function term that captures a specific class of redox reactions. In these reactions, an aldehyde or ketone (oxo) group serves as the hydrogen or electron donor, while a disulfide bond acts as the electron acceptor. This chemistry is central to enzymes that couple substrate oxidation to the reduction of protein disulfides, often as part of broader metabolic or stress-response pathways. Researchers study this term because it defines the catalytic logic of enzymes that control polyamine catabolism, selenium-dependent redox balance, and cellular responses to oxidative stress [1,5]. The term is distinct from other oxidoreductase activities because it explicitly requires a disulfide as the terminal electron acceptor, rather than NAD(P)+, FAD, or molecular oxygen. This specificity makes GO:0016624 a useful annotation for genes whose products participate in thiol-disulfide exchange reactions linked to aldehyde or ketone oxidation. Understanding which genes carry this activity, and how mutations alter it, is critical for interpreting disease-associated variants and for designing targeted experiments [3,8].
oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor At A Glance
| GO ID | GO:0016624 |
|---|---|
| GO term | oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor |
| Ontology | molecular_function |
| Synonym | oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulphide as acceptor |
| Major function | Catalyzes redox reactions where an aldehyde or oxo group donates electrons and a disulfide is reduced |
| Electron donor | Aldehyde or ketone (oxo) group |
| Electron acceptor | Disulfide bond |
| Reaction type | Oxidation-reduction (redox) |
| Related processes | Polyamine catabolism, selenium-dependent redox regulation, oxidative stress response [1,5] |
What Is GO:0016624?
GO:0016624 is defined as catalysis of an oxidation-reduction (redox) reaction in which an aldehyde or ketone (oxo) group acts as a hydrogen or electron donor and reduces a disulfide. In other words, the enzyme takes electrons from an aldehyde or oxo substrate and transfers them to a disulfide bond, thereby reducing the disulfide while oxidizing the donor. This definition is based on the QuickGO entry for GO:0016624, which also lists the synonym oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulphide as acceptor.
Why Is oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor Important in Cell Biology?
GO:0016624 is important because it defines a catalytic activity that connects aldehyde or ketone metabolism to disulfide reduction, a process that influences redox homeostasis, polyamine catabolism, and cellular stress responses [1,5]. Enzymes with this activity can modulate the balance between oxidized and reduced thiols, which in turn affects protein function, signaling, and cell survival. Dysregulation of these enzymes has been implicated in cancer, renal failure, and metabolic disorders, making them attractive targets for mechanistic studies and therapeutic development [3,8].
• Defines a specific redox mechanism that links aldehyde/oxo oxidation to disulfide reduction.
• Encompasses selenium-dependent enzymes involved in antioxidant defense and redox signaling.
• Includes polyamine oxidases that regulate polyamine levels and produce reactive aldehydes such as acrolein [3,5].
• Dysregulation is associated with gastric carcinogenesis through acrolein production.
• Altered polyamine catabolism is observed in renal failure and other metabolic stress conditions.
• Provides a functional annotation for genes that may be misannotated as generic oxidoreductases.
• Supports the design of selective inhibitors for multi-specific enzymes.
• Enables CRISPR-based dissection of catalytic versus non-catalytic roles in disease models [3,8].
• Helps interpret variants in genes such as spermine oxidase and related enzymes [3,5].
• Guides research on thiol-disulfide exchange in cancer and metabolic disease [5,8].
What Happens During oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor?
Substrate recognition and binding
In simple terms: The enzyme first grabs the aldehyde or ketone substrate and positions it for reaction.
Enzymes with GO:0016624 activity bind an aldehyde or ketone (oxo) substrate in a pocket that stabilizes the carbonyl group and facilitates hydride or electron transfer. For polyamine oxidases, the substrate is often a polyamine that is oxidized at a carbon adjacent to a nitrogen, generating an aldehyde intermediate. The binding step is critical for specificity, as these enzymes can act on multiple substrates, and differential inhibition studies have highlighted intra-site differences that affect substrate preference.
Oxidation of the aldehyde or oxo group
In simple terms: The substrate loses electrons, becoming oxidized.
The catalytic cycle begins with oxidation of the aldehyde or oxo group, which donates electrons or hydrogen to the enzyme's active site. In selenium-dependent enzymes, this step often involves a selenocysteine residue that participates in electron transfer. For spermine oxidase, oxidation of spermine produces an aldehyde intermediate and hydrogen peroxide, linking this activity to oxidative stress [3,5].
Disulfide reduction and electron transfer
In simple terms: The electrons removed from the substrate are passed to a disulfide bond, which breaks.
The electrons generated from substrate oxidation are transferred to a disulfide bond within the enzyme or a partner protein, reducing it to two thiols. This step distinguishes GO:0016624 from other oxidoreductases that use NAD(P)+ or FAD as terminal acceptors. The reduction of the disulfide often triggers conformational changes that regulate enzyme activity or allow product release.
Product release and enzyme regeneration
In simple terms: The oxidized product leaves, and the enzyme resets for another round.
After disulfide reduction, the oxidized product is released, and the enzyme returns to its resting state, often through re-oxidation of the active-site thiols. In polyamine oxidases, the aldehyde product can be further metabolized to reactive species such as acrolein, which has been linked to gastric carcinogenesis. The regeneration step may be rate-limiting and is a target for differential inhibitors.
Integration with cellular redox networks
In simple terms: This activity is part of a larger web of redox reactions in the cell.
GO:0016624 activity is integrated with cellular redox networks, including glutathione and thioredoxin systems [1,5]. Selenium-dependent enzymes with this activity contribute to antioxidant defense and redox signaling. Polyamine catabolism via spermine oxidase generates hydrogen peroxide and aldehydes, which can modulate cell proliferation and death [3,5]. In renal failure, altered polyamine levels and oxidative stress are observed, suggesting a role for these enzymes in disease pathology.
Key Genes Involved in GO:0016624 oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor
The following genes and proteins are associated with GO:0016624 activity or related redox processes, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SMOX | Spermine oxidase; oxidizes spermine to spermidine and produces H2O2 and acrolein | Linked to gastric carcinogenesis and polyamine catabolism [3,5] |
| SAT1 | Spermidine/spermine N1-acetyltransferase; regulates polyamine catabolism | Indirectly affects substrates for GO:0016624 enzymes |
| PAOX | Peroxisomal polyamine oxidase; oxidizes N1-acetylspermine | Contributes to polyamine catabolism and redox balance |
| SELENBP1 | Selenium-binding protein 1; may participate in selenium-dependent redox reactions | Associated with selenium-dependent enzyme activity |
| GPX1 | Glutathione peroxidase 1; reduces hydrogen peroxide using glutathione | Selenium-dependent enzyme; related to redox homeostasis |
| GPX4 | Glutathione peroxidase 4; reduces lipid peroxides | Selenium-dependent enzyme; protects against oxidative stress |
| TXNRD1 | Thioredoxin reductase 1; reduces thioredoxin | Selenium-dependent enzyme; maintains thiol redox state |
| TXNRD2 | Thioredoxin reductase 2; mitochondrial isoform | Selenium-dependent enzyme; mitochondrial redox regulation |
| SELENOP | Selenoprotein P; selenium transport | Supports selenium-dependent enzyme function |
| SELENOF | Selenoprotein F; involved in ER redox | May influence disulfide reduction pathways |
| SELENOK | Selenoprotein K; ER membrane protein | Linked to ER redox and calcium signaling |
| SELENOS | Selenoprotein S; ER stress response | Modulates oxidative stress and inflammation |
| SELENOT | Selenoprotein T; thioredoxin-like | Potential role in redox regulation |
| SELENOW | Selenoprotein W; antioxidant | Associated with redox homeostasis |
| SELENOH | Selenoprotein H; nuclear redox | May affect transcription under oxidative stress |
| SELENOM | Selenoprotein M; ER redox | Linked to neuroprotection |
| SELENON | Selenoprotein N; ER redox | Mutations cause rigid spine muscular dystrophy |
| SELENOI | Selenoprotein I; phospholipid synthesis | Indirectly related to redox balance |
How Is oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor Regulated?
The activity of enzymes with GO:0016624 is regulated at multiple levels. Selenium availability controls the expression and activity of selenium-dependent oxidoreductases, as selenium is incorporated into selenocysteine. Polyamine levels regulate spermine oxidase expression and activity through substrate availability and feedback mechanisms. In renal failure, altered polyamine metabolism and oxidative stress can affect enzyme function. Additionally, post-translational modifications such as thiol oxidation and disulfide formation can modulate catalytic activity [1,5].
oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SMOX | Gastric cancer, acrolein-induced DNA damage | SMOX knockout gastric organoids or cell lines |
| SAT1 | Polyamine catabolism disorders | SAT1 overexpression or knockout cells |
| GPX1 | Oxidative stress, cancer | GPX1 knockout mice or cell lines |
| TXNRD1 | Cancer, redox imbalance | TXNRD1 inducible knockout cells |
| SELENBP1 | Metabolic stress, cancer | SELENBP1 overexpression models |
Cancer
Spermine oxidase (SMOX) promotes Helicobacter pylori-mediated gastric carcinogenesis through acrolein production, linking GO:0016624-related activity to DNA damage and tumorigenesis. Polyamine catabolism is frequently dysregulated in cancer, and enzymes that oxidize polyamines can generate reactive aldehydes that contribute to mutagenesis.
Renal failure
Polyamine levels are altered in renal failure, and oxidative stress associated with uremia may affect enzymes with GO:0016624 activity. Selenium-dependent enzymes also play a role in protecting renal tissue from oxidative damage.
Metabolic and oxidative stress disorders
Dysregulation of selenium-dependent oxidoreductases and polyamine oxidases can impair redox homeostasis, contributing to metabolic and oxidative stress-related pathologies [1,5]. Differential inhibition of multi-specific enzymes may offer therapeutic strategies.
From oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of SMOX reduce acrolein production? | SMOX knockout cell line |
| Does a point mutation in the active site abolish oxidoreductase activity? | Point-mutation knock-in via CRISPR |
| Can tagged SMOX reveal subcellular localization? | Knock-in of fluorescent tag |
| Does overexpression of GPX1 protect against oxidative stress? | GPX1 overexpression cell line |
| Which genes cooperate with GO:0016624 enzymes? | CRISPR library screening |
| Does selenium deprivation alter enzyme activity? | Selenium-free media with knockout models |
How to Study the oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout | Loss of gene function | Phenotypic analysis of SMOX or GPX1 [3,5] |
| Point mutation knock-in | Effect of catalytic residue mutation | Separating enzymatic from non-enzymatic roles |
| Overexpression | Gain of function | Rescue experiments or stress protection |
| Metabolomics | Polyamine and acrolein levels | Quantifying pathway flux [3,5] |
| Redox profiling | Glutathione/thioredoxin status | Assessing oxidative stress |
| CRISPR library screening | Genetic interactions | Identifying synthetic lethal partners |
| Bioinformatics | Pathway enrichment | Interpreting omics data for GO:0016624 |
CRISPR knockout and point mutation
CRISPR-Cas9 knockout of genes such as SMOX can reveal loss-of-function phenotypes, while point mutations in catalytic residues can separate enzymatic activity from scaffolding functions [3,5].
Overexpression and knock-in
Overexpression of wild-type or mutant enzymes, or knock-in of tagged versions, allows assessment of localization, stability, and substrate specificity [1,5].
Metabolomics and redox profiling
Mass spectrometry-based metabolomics can measure polyamine levels, acrolein adducts, and glutathione redox state to quantify GO:0016624 activity in cells [3,5].
Library screening and bioinformatics
CRISPR library screens combined with bioinformatics can identify synthetic lethal interactions and pathways that depend on GO:0016624 enzymes.
How CRISPR Can Be Used to Study GO:0016624 oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor
Knockout
CRISPR knockout of SMOX or other GO:0016624-related genes can abolish enzymatic activity and reveal effects on polyamine catabolism, acrolein production, and cell survival [3,5].
Point Mutation
Introducing point mutations in catalytic residues, such as selenocysteine or active-site cysteines, can distinguish redox catalysis from other functions.
Knock-in
Knock-in of epitope tags or fluorescent proteins allows tracking of enzyme localization and interactions in live cells.
Overexpression
Overexpression of wild-type or mutant enzymes can test gain-of-function effects, such as protection against oxidative stress or enhanced acrolein production [1,3].
How EDITGENE Supports oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor Research
Researchers studying oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor-related genes often need to determine whether a candidate gene is causally involved in a specific phenotype. EDITGENE provides the CRISPR tools and cell models to answer these questions with rigor and reproducibility.
Contact EDITGENE today to design your custom CRISPR model for oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor research.
Frequently Asked Questions About oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor
What is GO:0016624?
GO:0016624 is a Gene Ontology molecular function term for oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor. It describes redox reactions where an aldehyde or ketone donates electrons and a disulfide is reduced.
What genes are involved in oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor?
Genes include SMOX, GPX1, TXNRD1, and other selenium-dependent enzymes and polyamine oxidases [1,3,5].
What diseases are linked to GO:0016624?
Dysregulation has been linked to gastric cancer through acrolein production, renal failure, and oxidative stress disorders [3,5,8].
How can I study GO:0016624 in the lab?
CRISPR knockout, point mutation, knock-in, overexpression, metabolomics, and redox profiling are common approaches [1,3,5].
What is the role of SMOX in cancer?
SMOX promotes Helicobacter pylori-mediated gastric carcinogenesis through acrolein production, linking polyamine oxidation to DNA damage.
Why are selenium-dependent enzymes important for GO:0016624?
Selenium-dependent enzymes often use selenocysteine to catalyze redox reactions, including disulfide reduction.
Can CRISPR help identify GO:0016624-related pathways?
Yes, CRISPR library screening can identify genetic interactions and pathways that depend on these enzymes.
What are the substrates of GO:0016624 enzymes?
Substrates include aldehydes and ketones, such as polyamines in the case of spermine oxidase.
How is GO:0016624 regulated?
Regulation occurs through selenium availability, substrate levels, and post-translational modifications of active-site thiols [1,5].
What model systems are used to study GO:0016624?
Cell lines, organoids, and mouse models with knockout or knock-in of genes like SMOX and GPX1 are commonly used [3,5].
Conclusion
GO:0016624 defines a distinct redox activity that couples aldehyde or ketone oxidation to disulfide reduction, with critical roles in polyamine catabolism, selenium-dependent antioxidant defense, and disease processes such as gastric cancer and renal failure [1,3,5,8]. Understanding the genes and mechanisms underlying this activity requires robust experimental models. EDITGENE provides comprehensive CRISPR services to accelerate research on GO:0016624-related pathways.
References
- 1. Stadtman TC. 1980. Selenium-dependent enzymes.. Annu Rev Biochem 49:93-110 PMID: 6996574
- 3. McNamara KM et al.. 2025. Spermine oxidase promotes Helicobacter pylori-mediated gastric carcinogenesis through acrolein production.. Oncogene 44(5):296-306 PMID: 39523394
- 4. Cappiello M et al.. 2020. Intra-site differential inhibition of multi-specific enzymes.. J Enzyme Inhib Med Chem 35(1):840-846 PMID: 32208768
- 5. Casero RA et al.. 2009. Polyamine catabolism and disease.. Biochem J 421(3):323-38 PMID: 19589128
- 8. Igarashi K et al.. 2006. Polyamines in renal failure.. Amino Acids 31(4):477-83 PMID: 16554974
