GO:0016638 oxidoreductase activity, acting on the CH-NH2 group of donors: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0016638 describes a molecular function: catalysis of a redox reaction where a CH-NH2 group donates hydrogen or electrons to an acceptor [1, 5].
• This activity is central to amine metabolism, including oxidative deamination of primary amines and histone demethylation [1, 3].
• Key enzyme families include flavin-dependent amine oxidases (e.g., LSD1/KDM1A, primary amine oxidase) and NAD(P)-dependent amine dehydrogenases [1, 3, 5].
• Dysregulation is linked to cancer, neurological disorders, and metabolic diseases, making these enzymes therapeutic targets [1, 2].
• CRISPR knockout, point mutation, knock-in, and overexpression models enable causal dissection of GO:0016638 enzyme function [1, 5].
• EDITGENE provides end-to-end CRISPR services and bioinformatics to study GO:0016638-related genes in any cell type.
Description
GO:0016638, oxidoreductase activity, acting on the CH-NH2 group of donors, is a molecular function term in the Gene Ontology that defines enzymes catalyzing redox reactions where a CH-NH2 group serves as the electron donor [1, 5]. This activity is fundamental to amine catabolism, neurotransmitter regulation, and epigenetic control, as exemplified by flavin-dependent amine oxidases and dehydrogenases [1, 3, 5]. Researchers study this term to understand metabolic pathways, chromatin remodeling, and disease mechanisms, and to develop inhibitors or engineered enzymes for biotechnology [1, 3, 5]. The term encompasses diverse proteins, from histone demethylases like LSD1 to primary amine oxidases, all sharing the common chemistry of CH-NH2 oxidation [1, 3].
oxidoreductase activity, acting on the CH-NH2 group of donors At A Glance
| GO ID | GO:0016638 |
|---|---|
| GO term | oxidoreductase activity, acting on the CH-NH2 group of donors |
| Ontology | molecular_function |
| Synonym | oxidoreductase activity, acting on the CH-NH2 group of donors, other acceptors |
| Major function | Catalysis of redox reactions where a CH-NH2 group is the electron donor |
| Cofactors | Flavin (FAD/FMN) or NAD(P)+ commonly involved [1, 5] |
| Representative enzymes | LSD1/KDM1A, primary amine oxidase, amine dehydrogenases [1, 3, 5] |
| Biological context | Amine metabolism, histone demethylation, neurotransmitter degradation [1, 3] |
What Is GO:0016638?
According to QuickGO, GO:0016638 is defined as catalysis of an oxidation-reduction (redox) reaction in which a CH-NH2 group acts as a hydrogen or electron donor and reduces a hydrogen or electron acceptor. In simpler terms, it is an enzyme activity that removes electrons from a CH-NH2 group and transfers them to another molecule, often using flavin or NAD(P) cofactors [1, 5].
Why Is oxidoreductase activity, acting on the CH-NH2 group of donors Important in Cell Biology?
GO:0016638 is important because it governs fundamental biochemical processes such as oxidative deamination of primary amines, which is critical for neurotransmitter homeostasis and metabolic flux. It also includes histone demethylases like LSD1, which regulate chromatin structure and gene expression, impacting development and cancer. Understanding this activity aids in drug discovery, as inhibitors of these enzymes are explored for cancer and neurological disorders [1, 3]. Moreover, engineered amine dehydrogenases are valuable for biocatalysis in producing chiral amines.
• Regulates neurotransmitter levels via amine oxidase activity, relevant to neurological disorders.
• Controls epigenetic marks through histone demethylation, influencing gene expression.
• Involved in metabolic reprogramming and oxidative stress responses.
• Target for cancer therapy, e.g., LSD1 inhibitors in clinical trials.
• Enables biocatalytic synthesis of chiral amines for pharmaceuticals.
• Linked to plant defense and ROS signaling via polyamine oxidase.
• Contributes to bacterial quorum sensing and virulence [4, 8].
• Provides a model for studying enzyme promiscuity and evolution.
• Facilitates redox balance in mitochondria and peroxisomes.
• Offers opportunities for CRISPR-based functional genomics [1, 5].
What Happens During oxidoreductase activity, acting on the CH-NH2 group of donors?
Substrate Binding and CH-NH2 Recognition
In simple terms: The enzyme grabs a molecule that has a CH-NH2 group, like an amine, and positions it for reaction.
Enzymes with GO:0016638 activity bind substrates containing a CH-NH2 group, such as primary amines or lysine residues in histones [1, 3]. For example, LSD1 recognizes methylated lysine in histone H3, while primary amine oxidase binds small amines like tyramine [1, 3]. Binding often involves conserved aromatic residues that orient the CH-NH2 group toward the catalytic cofactor.
Electron Transfer and Cofactor Reduction
In simple terms: Electrons are pulled off the CH-NH2 group and passed to a helper molecule, usually a flavin or NAD(P).
The CH-NH2 group donates electrons, reducing a cofactor such as FAD in amine oxidases or NAD(P)+ in dehydrogenases [1, 5]. In flavin-dependent enzymes, the reduced flavin is subsequently reoxidized by molecular oxygen or another acceptor, generating hydrogen peroxide or water [1, 3]. Amine dehydrogenases transfer hydride directly to NAD(P)+, producing ammonia and a carbonyl product.
Product Release and Enzyme Regeneration
In simple terms: The modified substrate leaves, and the enzyme resets to its original state to start another cycle.
After oxidation, the product (e.g., an aldehyde or imine) is released, and the enzyme returns to its oxidized state, either spontaneously or via electron transfer chains [1, 5]. For LSD1, the demethylated histone product remains bound until release, allowing chromatin modification. Regeneration may involve ancillary proteins or electron carriers in vivo.
Key Genes Involved in GO:0016638 oxidoreductase activity, acting on the CH-NH2 group of donors
The following genes encode enzymes with GO:0016638 activity or directly regulate this function, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| KDM1A (LSD1) | Flavin-dependent histone demethylase; oxidizes CH-NH2 in methylated lysines | Epigenetic regulation, cancer stemness, drug target |
| AOC1 (DAO) | Copper amine oxidase; oxidizes primary amines | Histamine metabolism, allergy, neurological studies |
| AOC2 | Retina-specific amine oxidase; oxidizes CH-NH2 donors | Retinal function, amine metabolism |
| AOC3 (VAP-1) | Semicarbazide-sensitive amine oxidase; oxidizes primary amines | Inflammation, diabetes, adhesion |
| MAOA | Mitochondrial amine oxidase; degrades neurotransmitters | Neurological disorders, antidepressant target |
| MAOB | Mitochondrial amine oxidase; degrades dopamine | Parkinson's disease, neuroprotection |
| PAOX | Peroxisomal amine oxidase; oxidizes polyamines | Polyamine catabolism, ROS production |
| SMOX | Spermine oxidase; oxidizes spermine | Cancer, oxidative stress |
| IL4I1 | L-amino acid oxidase; oxidizes CH-NH2 donors | Immune regulation, schizophrenia genetics |
| DDO | D-aspartate oxidase; oxidizes D-aspartate | Neurotransmission, aging |
| PIPOX | Pipecolate oxidase; oxidizes pipecolate | Lysine metabolism, epilepsy |
| GLDC | Glycine decarboxylase; oxidizes glycine | Metabolic reprogramming, fibrosis |
| PRODH | Proline dehydrogenase; oxidizes proline | Redox balance, cancer metabolism |
| DAO1 (plant) | Polyamine oxidase; oxidizes polyamines | Plant defense, ROS signaling |
| RBOHD | Regulated by PAO activity; produces ROS | Plant immunity, oxidative burst |
| AlgR | Regulates amine oxidase genes in Pseudomonas | Bacterial virulence, biofilm |
| Hfq | RNA chaperone affecting amine metabolism genes | Quorum sensing, stress response |
| KDM1B | Flavin-dependent demethylase; oxidizes CH-NH2 | Epigenetics, development |
How Is oxidoreductase activity, acting on the CH-NH2 group of donors Regulated?
GO:0016638 activity is regulated at multiple levels. Transcriptional control includes Hfq-dependent regulation in bacteria, where Hfq alters expression of amine metabolism genes. In Pseudomonas aeruginosa, AlgR regulates genes involved in amine oxidation, impacting virulence. In eukaryotes, LSD1 activity is modulated by interaction partners and post-translational modifications. Mitochondrial calcium uniporter regulates PGC-1α, which can influence metabolic enzymes including amine oxidases. Plant polyamine oxidase activity is feedback-regulated by ROS and RBOH activity.
oxidoreductase activity, acting on the CH-NH2 group of donors and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| KDM1A | Cancer, epigenetic dysregulation | Knockout and point mutation in cancer cell lines |
| MAOA | Depression, aggression | Knockout mice, overexpression in neurons |
| MAOB | Parkinson's disease | Knock-in of human variants in mice |
| IL4I1 | Schizophrenia | CRISPR knockout in iPSC-derived neurons |
| SMOX | Cancer, oxidative stress | Overexpression in epithelial cells |
Cancer
LSD1 (KDM1A) is overexpressed in many cancers and promotes tumorigenesis by demethylating histones. Inhibitors of LSD1 are in clinical trials for leukemia and solid tumors. Other amine oxidases, such as SMOX, contribute to oxidative stress and cancer progression.
Neurological Disorders
Monoamine oxidases MAOA and MAOB degrade neurotransmitters; their dysregulation is linked to depression, Parkinson's disease, and schizophrenia. IL4I1 has been implicated in schizophrenia genetics through transcriptomic and machine learning analyses. D-aspartate oxidase (DDO) affects NMDA receptor signaling and is studied in neurodegeneration.
Metabolic and Fibrotic Diseases
Mitochondrial calcium uniporter regulates PGC-1α and metabolic reprogramming in pulmonary fibrosis, involving oxidoreductases. Glycine decarboxylase (GLDC) and proline dehydrogenase (PRODH) support metabolic shifts in fibrosis and cancer.
From oxidoreductase activity, acting on the CH-NH2 group of donors-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of KDM1A affect proliferation? | CRISPR knockout in cancer cell lines |
| How do point mutations in MAOB alter substrate specificity? | CRISPR point mutation knock-in in SH-SY5Y cells |
| Can overexpression of SMOX induce ROS? | CRISPR overexpression in HEK293T |
| What is the role of IL4I1 in neuronal function? | Knockout in iPSC-derived neurons |
| Does tagged LSD1 rescue demethylation? | Knock-in of FLAG-tagged KDM1A |
| How does AlgR regulate amine oxidase genes? | CRISPR interference in Pseudomonas |
How to Study the oxidoreductase activity, acting on the CH-NH2 group of donors Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Gene expression changes | Identify GO:0016638 gene signatures in disease |
| CRISPR knockout screen | Gene essentiality and pathway dependencies | Discover regulators of amine oxidation |
| Enzyme activity assay | Catalytic rate and substrate specificity | Characterize mutant enzymes [3, 5] |
| ChIP-seq | Histone modification and LSD1 binding | Map demethylation targets |
| Metabolomics | Amine and metabolite levels | Assess pathway flux |
| Western blot | Protein expression and modification | Validate knockout or overexpression |
| Proteomics | Protein interactions and abundance | Identify cofactor partners |
| Machine learning | Predictive modeling from omics data | Link genotypes to phenotypes |
Transcriptomics and Machine Learning
RNA-seq combined with machine learning can identify expression signatures of GO:0016638 genes in disease cohorts, as shown in schizophrenia post-mortem brain studies. This approach reveals co-expression networks and potential biomarkers.
Enzyme Activity Assays
Colorimetric or fluorometric assays measure amine oxidase or dehydrogenase activity using substrates like tyramine or methylated histones [3, 5]. These assays quantify kinetic parameters and inhibitor efficacy [3, 5].
CRISPR Screening
Genome-wide CRISPR knockout screens can identify genes required for GO:0016638 activity or resistance to inhibitors. Libraries targeting epigenetic regulators are particularly useful.
Structural and Biophysical Methods
X-ray crystallography and cryo-EM reveal substrate binding and cofactor geometry in amine oxidases and dehydrogenases [1, 5]. These methods guide rational inhibitor design.
How CRISPR Can Be Used to Study GO:0016638 oxidoreductase activity, acting on the CH-NH2 group of donors
Knockout
CRISPR knockout of GO:0016638 genes (e.g., KDM1A, MAOA) ablates enzyme activity, enabling studies of loss-of-function phenotypes in cancer, neurons, or immune cells [1, 3]. Knockout cell lines are essential for validating drug targets.
Point Mutation
Introducing specific point mutations (e.g., catalytic residues in LSD1 or MAOB) via CRISPR base editing or HDR reveals structure-function relationships and disease-associated variants [1, 3]. This approach distinguishes catalytic activity from scaffolding functions.
Knock-in
Knock-in of tagged versions (e.g., FLAG-LSD1) or disease alleles allows tracking of endogenous protein localization and dynamics. Knock-in models also enable conditional rescue experiments.
Overexpression
CRISPR activation or cDNA overexpression of GO:0016638 enzymes (e.g., SMOX, IL4I1) tests gain-of-function effects on ROS, metabolism, or immune evasion [2, 7]. Overexpression models are useful for drug screening.
How EDITGENE Supports oxidoreductase activity, acting on the CH-NH2 group of donors Research
Researchers studying oxidoreductase activity, acting on the CH-NH2 group of donors-related genes often need to determine whether a candidate gene is causally involved in a specific pathway or disease. EDITGENE provides tailored CRISPR cell models and bioinformatics to accelerate this discovery.
Contact EDITGENE today to design your custom CRISPR model for oxidoreductase activity, acting on the CH-NH2 group of donors research.
Frequently Asked Questions About oxidoreductase activity, acting on the CH-NH2 group of donors
What is GO:0016638?
GO:0016638 is a Gene Ontology molecular function term for oxidoreductase activity acting on CH-NH2 group of donors, catalyzing redox reactions where a CH-NH2 group donates electrons [1, 5].
What enzymes have oxidoreductase activity acting on CH-NH2 group of donors?
Enzymes include histone demethylases like LSD1/KDM1A, primary amine oxidases (AOC1-3), monoamine oxidases (MAOA/B), and amine dehydrogenases [1, 3, 5].
What genes are involved in GO:0016638?
Key genes include KDM1A, MAOA, MAOB, AOC1, AOC2, AOC3, SMOX, PAOX, IL4I1, DDO, PIPOX, GLDC, and PRODH [1, 2, 3, 6, 7].
How is oxidoreductase activity acting on CH-NH2 group of donors regulated?
Regulation occurs via transcription factors (e.g., AlgR, Hfq), post-translational modifications, and cofactor availability [1, 4, 8].
What diseases are linked to GO:0016638?
Cancers, neurological disorders (depression, Parkinson's, schizophrenia), and metabolic/fibrotic diseases are linked [1, 2, 3, 6].
How can I study GO:0016638 in the lab?
Use CRISPR knockout, point mutation, knock-in, overexpression, enzyme assays, RNA-seq, and proteomics [1, 3, 5].
What is the role of LSD1 in GO:0016638?
LSD1 (KDM1A) is a flavin-dependent histone demethylase that oxidizes methylated lysines, regulating chromatin and cancer.
Can CRISPR screen identify GO:0016638 regulators?
Yes, genome-wide CRISPR screens can uncover genes required for amine oxidase activity or inhibitor resistance.
What model systems are used for GO:0016638 research?
Cancer cell lines, iPSC-derived neurons, mouse models, and plant systems are commonly used [1, 2, 3, 7].
How does EDITGENE support GO:0016638 research?
EDITGENE offers custom CRISPR knockout, point mutation, knock-in, overexpression, library screening, and bioinformatics services.
Conclusion
GO:0016638, oxidoreductase activity acting on the CH-NH2 group of donors, is a versatile molecular function central to amine metabolism, epigenetics, and disease. Its enzymes are promising therapeutic targets and biocatalysts. CRISPR-based models and multi-omics approaches are essential to dissect their roles, and EDITGENE provides the tools to accelerate this research.
References
- 1. Forneris F et al.. 2009. New roles of flavoproteins in molecular cell biology: histone demethylase LSD1 and chromatin.. FEBS J 276(16):4304-12 PMID: 19624733
- 2. Qi B et al.. 2022. Transcriptomics and machine learning to advance schizophrenia genetics: A case-control study using post-mortem brain data.. Comput Methods Programs Biomed 214:106590 PMID: 34954633
- 3. Shanahan P et al.. 2019. Theobromine and related methylxanthines as inhibitors of Primary Amine Oxidase.. J Food Biochem 43(2):e12697 PMID: 31353656
- 4. Sonnleitner E et al.. 2006. Hfq-dependent alterations of the transcriptome profile and effects on quorum sensing in Pseudomonas aeruginosa.. Mol Microbiol 59(5):1542-58 PMID: 16468994
- 5. Tseliou V et al.. 2019. Mechanistic Insight into the Catalytic Promiscuity of Amine Dehydrogenases: Asymmetric Synthesis of Secondary and Primary Amines.. Chembiochem 20(6):800-812 PMID: 30489013
- 6. Gu L et al.. 2019. Mitochondrial calcium uniporter regulates PGC-1α expression to mediate metabolic reprogramming in pulmonary fibrosis.. Redox Biol 26:101307 PMID: 31473487
- 7. Jasso-Robles FI et al.. 2020. Decrease of Arabidopsis PAO activity entails increased RBOH activity, ROS content and altered responses to Pseudomonas.. Plant Sci 292:110372 PMID: 32005378
- 8. Lizewski SE et al.. 2004. Identification of AlgR-regulated genes in Pseudomonas aeruginosa by use of microarray analysis.. J Bacteriol 186(17):5672-84 PMID: 15317771
