GO:0047313 aromatic-amino-acid:glyoxylate transaminase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0047313 describes the molecular function of catalyzing the reversible transfer of an amino group from an aromatic L-alpha-amino acid to glyoxylate, yielding an aromatic oxo-acid and glycine.
• The enzyme responsible for this activity was first purified and characterized from monkey and rat liver, where it participates in aromatic amino acid catabolism and glycine metabolism.
• This transaminase activity links aromatic amino acid breakdown to glyoxylate detoxification and glycine biosynthesis, pathways relevant to metabolic disorders and cancer metabolism.
• Research on GO:0047313 relies on enzymatic assays, CRISPR knockout models, and metabolomic profiling to dissect its role in cellular metabolism.
• Dysregulation of aromatic-amino-acid:glyoxylate transaminase activity may contribute to hyperoxaluria, neurological dysfunction, and tumor metabolic reprogramming, though direct evidence remains limited.
• EDITGENE provides CRISPR knockout, point-mutation, knock-in, and overexpression cell models to study GO:0047313-related genes in a publication-ready format.
Description
Aromatic-amino-acid:glyoxylate transaminase activity (GO:0047313) is a molecular function defined by the catalytic transfer of an amino group from an aromatic L-alpha-amino acid to glyoxylate, producing an aromatic oxo-acid and glycine. This enzymatic reaction sits at the intersection of aromatic amino acid catabolism and one-carbon/glycine metabolism, making it a focal point for researchers studying metabolic flux, nitrogen balance, and detoxification pathways. The activity was biochemically characterized in mammalian liver, where it contributes to the breakdown of phenylalanine, tyrosine, and tryptophan while simultaneously converting glyoxylate to glycine. Understanding this function is essential for interpreting metabolic phenotypes in genetic and pharmacological studies targeting aromatic amino acid metabolism. In this article, we synthesize the authoritative QuickGO definition with verified literature to provide a research-grade overview of GO:0047313, its mechanism, associated genes, disease relevance, and modern CRISPR-based methods for functional interrogation.
aromatic-amino-acid:glyoxylate transaminase activity At A Glance
| GO ID | GO:0047313 |
|---|---|
| GO term | aromatic-amino-acid:glyoxylate transaminase activity |
| Ontology | molecular_function |
| Synonym | aromatic-amino-acid--glyoxylate aminotransferase activity; aromatic-amino-acid-glyoxylate aminotransferase activity; aromatic-amino-acid:glyoxylate aminotransferase activity; aromatic-amino-acid-glyoxylate transaminase activity |
| Definition | Catalysis of the reaction: an aromatic L-alpha-amino acid + glyoxylate = an aromatic oxo-acid + glycine. |
| Major function | Transamination between aromatic amino acids and glyoxylate, linking aromatic amino acid catabolism to glycine synthesis. |
| Cofactor | Pyridoxal 5'-phosphate (PLP) dependent, as typical for transaminases. |
| Subcellular location | Not specified in QuickGO; enzymatic activity was characterized in liver tissue. |
| Reaction direction | Reversible; can operate in both amino group donation and acceptance depending on substrate availability. |
What Is GO:0047313?
GO:0047313, aromatic-amino-acid:glyoxylate transaminase activity, is defined as the catalysis of the reaction: an aromatic L-alpha-amino acid + glyoxylate = an aromatic oxo-acid + glycine. In other words, the enzyme transfers the alpha-amino group from an aromatic amino acid (such as phenylalanine, tyrosine, or tryptophan) to glyoxylate, generating the corresponding aromatic alpha-keto acid and glycine. This is a pyridoxal phosphate-dependent transamination reaction that is reversible and operates in both catabolic and anaplerotic contexts.
Why Is aromatic-amino-acid:glyoxylate transaminase activity Important in Cell Biology?
GO:0047313 is important because it connects two critical metabolic nodes: aromatic amino acid catabolism and glyoxylate/glycine metabolism. Aromatic amino acids are precursors for neurotransmitters, hormones, and redox regulators, while glyoxylate is a toxic metabolite that must be detoxified to prevent oxalate accumulation. By transferring nitrogen from aromatic amino acids to glyoxylate, this activity simultaneously supports amino acid breakdown and glycine production, influencing nitrogen disposal, one-carbon metabolism, and cellular antioxidant capacity. Consequently, researchers studying inborn errors of metabolism, liver function, cancer metabolic reprogramming, and neurochemistry need to understand this enzymatic function to interpret metabolic phenotypes and design targeted experiments.
• Links aromatic amino acid catabolism to glycine biosynthesis, affecting one-carbon metabolism and glutathione production.
• Contributes to glyoxylate detoxification, reducing the risk of oxalate crystal formation and hyperoxaluria.
• Modulates levels of aromatic amino acids and their neuroactive derivatives, with potential implications for neurological function.
• Provides a metabolic route for nitrogen disposal from aromatic amino acids in liver and other tissues.
• May influence cancer cell metabolism by supporting glycine supply for nucleotide synthesis and redox balance.
• Serves as a potential biomarker or therapeutic target in metabolic disorders involving aromatic amino acids or glyoxylate.
• Enables researchers to study enzyme kinetics, substrate specificity, and inhibitor design for transaminases.
• Facilitates cross-species comparisons of aromatic amino acid metabolism in mammals.
• Supports systems biology modeling of hepatic nitrogen and carbon flux.
• Offers a target for CRISPR-based functional genomics to dissect metabolic networks.
What Happens During aromatic-amino-acid:glyoxylate transaminase activity?
Substrate Binding and Schiff Base Formation
In simple terms: The enzyme grabs an aromatic amino acid and a glyoxylate molecule, then uses a helper molecule to swap an amino group.
The catalytic cycle begins with the binding of an aromatic L-alpha-amino acid (e.g., phenylalanine, tyrosine, or tryptophan) and glyoxylate to the enzyme active site. The enzyme uses pyridoxal 5'-phosphate (PLP) as a cofactor, which forms a Schiff base with the alpha-amino group of the aromatic amino acid. This intermediate facilitates the transfer of the amino group to the PLP cofactor, generating a pyridoxamine 5'-phosphate (PMP) form and releasing the aromatic oxo-acid.
Amino Group Transfer to Glyoxylate
In simple terms: The amino group picked up by the helper molecule is then handed over to glyoxylate, turning it into glycine.
In the second half of the reaction, the PMP form of the enzyme binds glyoxylate. The amino group is transferred from PMP to glyoxylate, yielding glycine and regenerating the PLP form of the enzyme. This ping-pong bi-bi mechanism is characteristic of transaminases and allows the enzyme to catalyze the reversible interconversion of aromatic amino acids and their corresponding oxo-acids with glyoxylate and glycine.
Product Release and Enzyme Regeneration
In simple terms: The products, an aromatic oxo-acid and glycine, are released, and the enzyme is ready to start again.
Following the transfer, the aromatic oxo-acid and glycine are released from the active site. The enzyme returns to its PLP-bound resting state, ready for another catalytic cycle. The reaction is reversible, so the enzyme can also catalyze the reverse reaction: transferring an amino group from glycine to an aromatic oxo-acid to regenerate the aromatic amino acid. The direction of flux depends on substrate concentrations and cellular metabolic demands.
Physiological Context and Metabolic Integration
In simple terms: This reaction helps the body break down aromatic amino acids and make glycine, connecting different metabolic pathways.
Physiologically, this activity integrates aromatic amino acid catabolism with glycine biosynthesis and glyoxylate detoxification. In liver, it contributes to the disposal of excess aromatic amino acids and the production of glycine, which is used for glutathione synthesis, collagen formation, and one-carbon metabolism. The enzyme was purified from monkey and rat liver, confirming its presence in mammalian hepatic tissue. Its dual role in nitrogen handling and glyoxylate detoxification makes it relevant to metabolic disorders such as hyperoxaluria and to cancer metabolism, where glycine demand is high.
Key Genes Involved in GO:0047313 aromatic-amino-acid:glyoxylate transaminase activity
The following genes and proteins are directly or indirectly associated with aromatic-amino-acid:glyoxylate transaminase activity (GO:0047313) based on biochemical characterization and metabolic pathway context.
| Gene | Major Role | Research Relevance |
|---|---|---|
| Aromatic-amino-acid:glyoxylate aminotransferase (unnamed in PMID 25837) | Catalyzes the transamination between aromatic amino acids and glyoxylate | Directly defines GO:0047313; purified from monkey and rat liver |
| TAT (Tyrosine aminotransferase) | Catalyzes tyrosine transamination, overlapping substrate specificity | Potential compensatory or overlapping activity in aromatic amino acid metabolism |
| HPD (4-Hydroxyphenylpyruvate dioxygenase) | Degrades tyrosine-derived 4-hydroxyphenylpyruvate | Downstream of aromatic amino acid transamination |
| HGD (Homogentisate 1,2-dioxygenase) | Degrades homogentisate in tyrosine catabolism | Links aromatic amino acid breakdown to disease (alkaptonuria) |
| FAH (Fumarylacetoacetate hydrolase) | Final step of tyrosine catabolism | Deficiency causes tyrosinemia type I |
| PAH (Phenylalanine hydroxylase) | Converts phenylalanine to tyrosine | Upstream of aromatic amino acid catabolism; mutations cause PKU |
| GOT1 (Aspartate aminotransferase, cytoplasmic) | Transaminase with broad substrate specificity | May share mechanistic features with GO:0047313 |
| GOT2 (Aspartate aminotransferase, mitochondrial) | Mitochondrial transaminase | Involved in nitrogen shuttling and aromatic amino acid metabolism |
| GPT (Alanine aminotransferase) | Transaminase for alanine and pyruvate | Model for PLP-dependent transamination mechanisms |
| AGXT (Alanine--glyoxylate aminotransferase) | Detoxifies glyoxylate to glycine | Mutations cause primary hyperoxaluria type 1; related glyoxylate metabolism |
| GRHPR (Glyoxylate reductase/hydroxypyruvate reductase) | Reduces glyoxylate to glycolate | Deficiency causes hyperoxaluria type 2; intersects with glyoxylate pool |
| HOGA1 (4-Hydroxy-2-oxoglutarate aldolase) | Mitochondrial glyoxylate metabolism | Mutations cause hyperoxaluria type 3 |
| SHMT1 (Serine hydroxymethyltransferase 1) | Produces glycine from serine | Contributes to glycine pool; intersects with one-carbon metabolism |
| SHMT2 (Serine hydroxymethyltransferase 2) | Mitochondrial glycine synthesis | Supports cancer cell glycine demand |
| GLDC (Glycine decarboxylase) | Degrades glycine in mitochondria | Regulates glycine flux; mutations cause non-ketotic hyperglycinemia |
| AMT (Aminomethyltransferase) | Glycine cleavage system component | Links glycine metabolism to one-carbon units |
| DHTKD1 (Dehydrogenase E1 and transketolase domain containing 1) | 2-oxoadipate dehydrogenase complex | Related to aromatic amino acid catabolism |
| KYNU (Kynureninase) | Tryptophan catabolism via kynurenine pathway | Connects aromatic amino acid breakdown to NAD+ synthesis |
How Is aromatic-amino-acid:glyoxylate transaminase activity Regulated?
The regulation of aromatic-amino-acid:glyoxylate transaminase activity is not well characterized at the transcriptional or post-translational level in the available literature. As a PLP-dependent enzyme, its activity may be influenced by pyridoxal 5'-phosphate availability, substrate concentrations (aromatic amino acids and glyoxylate), and product feedback (aromatic oxo-acids and glycine). Hormonal signals such as glucocorticoids, which induce several aminotransferases in liver, could potentially modulate its expression, but direct evidence is lacking. Metabolic flux through this reaction is likely governed by the cellular demand for glycine and the need to detoxify glyoxylate, as well as the availability of aromatic amino acids from diet or protein turnover.
aromatic-amino-acid:glyoxylate transaminase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| AGXT | Primary hyperoxaluria type 1; glyoxylate detoxification | HepG2 or HEK293T knockout of AGXT; oxalate measurement |
| GRHPR | Primary hyperoxaluria type 2; glyoxylate reductase deficiency | CRISPR knockout in renal epithelial cells; glyoxylate flux assay |
| HOGA1 | Primary hyperoxaluria type 3; mitochondrial glyoxylate metabolism | Hepatocyte-like cells with HOGA1 knockout; metabolomics |
| PAH | Phenylketonuria; aromatic amino acid catabolism | Patient-derived iPSCs; phenylalanine tolerance assay |
| TAT | Tyrosinemia type II; tyrosine transamination | Liver organoids with TAT knockout; tyrosine loading test |
Hyperoxaluria and Glyoxylate Metabolism Disorders
Aromatic-amino-acid:glyoxylate transaminase activity contributes to glyoxylate detoxification by converting it to glycine. When this activity is impaired, glyoxylate can accumulate and be oxidized to oxalate, leading to calcium oxalate crystal deposition in kidneys and other tissues. This mechanism is central to primary hyperoxaluria, particularly type 1 caused by AGXT mutations, and potentially to other forms of hyperoxaluria where glyoxylate handling is compromised. Although direct mutations in the gene encoding GO:0047313 have not been reported, its role in glyoxylate metabolism makes it a candidate modifier of oxalate-related pathology.
Aromatic Amino Acid Metabolism and Neurological Disorders
By participating in the catabolism of phenylalanine, tyrosine, and tryptophan, this transaminase activity influences the availability of aromatic amino acids for neurotransmitter synthesis. Perturbations in aromatic amino acid metabolism are associated with neurological conditions such as phenylketonuria, tyrosinemia, and disorders of monoamine metabolism. Altered flux through GO:0047313 could theoretically affect brain levels of dopamine, serotonin, and their metabolites, though direct evidence linking this specific activity to neurological disease remains to be established.
Cancer Metabolism and Glycine Dependency
Many cancer cells exhibit increased demand for glycine to support nucleotide biosynthesis and redox homeostasis. Aromatic-amino-acid:glyoxylate transaminase activity provides an alternative route for glycine production by transferring nitrogen from aromatic amino acids to glyoxylate. In tumors with high glycine consumption, upregulation of this activity could contribute to glycine supply, making it a potential metabolic vulnerability. However, experimental validation in cancer models is needed to confirm this hypothesis.
Liver Disease and Nitrogen Disposal
The liver is a major site of aromatic amino acid catabolism and nitrogen disposal. Enzymatic activity of GO:0047313 was characterized in liver tissue, suggesting a role in hepatic nitrogen balance. In liver diseases such as cirrhosis, altered aromatic amino acid metabolism contributes to hyperammonemia and encephalopathy. Modulating this transaminase activity could influence nitrogen flux, but its specific contribution to liver disease pathophysiology requires further investigation.
From aromatic-amino-acid:glyoxylate transaminase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of GO:0047313 activity alter glyoxylate and glycine levels? | CRISPR knockout of the responsible gene in HepG2 or primary hepatocytes; metabolomics |
| Can a point mutation in the active site abolish transaminase activity? | CRISPR point-mutation knock-in of catalytic residue in cell lines; enzyme assay |
| Does overexpression of the enzyme reduce oxalate production? | Stable overexpression in renal epithelial cells; oxalate quantification |
| How does the enzyme contribute to aromatic amino acid catabolism? | Knockout cells treated with labeled phenylalanine/tyrosine; flux analysis |
| What is the subcellular localization of the enzyme? | Tagged knock-in with fluorescent protein; confocal microscopy |
| Does the enzyme interact with other metabolic proteins? | Knock-in of affinity tags; immunoprecipitation and proteomics |
How to Study the aromatic-amino-acid:glyoxylate transaminase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Spectrophotometric transaminase assay | Enzyme activity via oxo-acid or glycine production | Kinetic characterization of purified enzyme or lysates |
| LC-MS/MS metabolomics | Levels of aromatic amino acids, oxo-acids, glycine, glyoxylate | Metabolic profiling of knockout or overexpression cells |
| Stable isotope tracing | Flux through transamination and glycine synthesis | Pathway analysis in liver cells or organoids |
| CRISPR knockout screening | Genes required for glyoxylate detoxification or glycine supply | Functional genomics in cancer or metabolic cell lines |
| Immunoprecipitation + MS | Protein interactions and post-translational modifications | Identification of enzyme complex components |
| Fluorescent tagging and microscopy | Subcellular localization of the enzyme | Live-cell imaging in knock-in cell lines |
| Enzyme-linked immunosorbent assay (ELISA) | Protein abundance of the enzyme | Validation of expression changes in disease models |
| RNA-seq | Transcriptional regulation of genes related to GO:0047313 | Expression profiling across tissues or conditions |
Enzymatic Activity Assays
Direct measurement of aromatic-amino-acid:glyoxylate transaminase activity can be performed using spectrophotometric or fluorometric assays that monitor the formation of aromatic oxo-acids or glycine. Typically, liver or cell lysates are incubated with aromatic amino acid substrates and glyoxylate, and the reaction is followed by coupling to NADH-consuming or NADPH-producing enzymes. Such assays were used in the original purification and characterization of the enzyme from monkey and rat liver.
Metabolomics and Flux Analysis
Untargeted or targeted metabolomics using LC-MS/MS can quantify aromatic amino acids, aromatic oxo-acids, glycine, and glyoxylate in cells or tissues. Stable isotope tracing with 13C- or 15N-labeled aromatic amino acids allows researchers to track flux through GO:0047313 and its contribution to glycine and oxalate pools. These methods are essential for linking enzyme activity to metabolic phenotypes in knockout or overexpression models.
CRISPR-Based Genetic Screens
Genome-wide CRISPR knockout or activation screens can identify genes that modulate glyoxylate toxicity or glycine dependency. Cells with reduced GO:0047313 activity may show altered sensitivity to glyoxylate or oxalate stress, enabling the discovery of synthetic lethal interactions. Such screens can be combined with metabolomic profiling to pinpoint metabolic vulnerabilities.
Proteomics and Enzyme Purification
Affinity purification coupled with mass spectrometry can identify the protein(s) responsible for GO:0047313 activity and their post-translational modifications. The original purification from monkey and rat liver used classical chromatography, but modern approaches employ tagged knock-in cell lines for rapid immunoprecipitation. Proteomic profiling can also reveal interaction partners and regulatory subunits.
How CRISPR Can Be Used to Study GO:0047313 aromatic-amino-acid:glyoxylate transaminase activity
Knockout
CRISPR knockout of the gene encoding aromatic-amino-acid:glyoxylate transaminase activity can be achieved by introducing frameshift mutations in early exons. Knockout cell lines are valuable for assessing the contribution of this activity to glyoxylate detoxification, glycine synthesis, and aromatic amino acid catabolism. Researchers can compare knockout and wild-type cells using metabolomics, enzyme assays, and growth assays under glyoxylate stress. EDITGENE provides validated knockout pools and clones for metabolic genes.
Point Mutation
Point mutations in the catalytic site or cofactor-binding residues can be introduced using CRISPR base editing or homology-directed repair. Such models allow precise dissection of the enzymatic mechanism, including substrate specificity and PLP binding. For example, mutating the lysine that forms the Schiff base with PLP would abolish activity, providing a negative control. EDITGENE offers custom point-mutation knock-in services for mechanistic studies.
Knock-in
Knock-in of epitope tags (e.g., FLAG, HA) or fluorescent proteins (e.g., GFP) at the endogenous locus enables visualization and affinity purification of the enzyme. Tagged knock-in cell lines facilitate localization studies, interaction proteomics, and real-time activity monitoring. EDITGENE provides tagged knock-in models with validated expression and localization.
Overexpression
Overexpression of the enzyme can be achieved by lentiviral transduction or CRISPR activation (CRISPRa). Overexpression models are useful for testing whether increased activity reduces glyoxylate toxicity, enhances glycine production, or alters aromatic amino acid flux. These models can also be used in drug discovery to screen for inhibitors or activators. EDITGENE offers stable overexpression cell lines and CRISPRa systems.
How EDITGENE Supports aromatic-amino-acid:glyoxylate transaminase activity Research
Researchers studying aromatic-amino-acid:glyoxylate transaminase activity-related genes often need to determine whether a candidate gene is causally involved in metabolic phenotypes such as glyoxylate detoxification, glycine supply, or aromatic amino acid catabolism. Establishing causality requires precise genetic manipulation, which is best achieved through CRISPR-based knockout, point mutation, knock-in, or overexpression models. EDITGENE specializes in providing these custom cell models along with functional validation and bioinformatics support, enabling researchers to move from correlation to mechanism efficiently.
Contact EDITGENE today to design your custom CRISPR model for aromatic-amino-acid:glyoxylate transaminase activity research.
Frequently Asked Questions About aromatic-amino-acid:glyoxylate transaminase activity
What is aromatic-amino-acid:glyoxylate transaminase activity?
It is a molecular function defined by GO:0047313, catalyzing the transfer of an amino group from an aromatic L-alpha-amino acid to glyoxylate, producing an aromatic oxo-acid and glycine.
What genes are involved in aromatic-amino-acid:glyoxylate transaminase activity?
The enzyme responsible was purified from monkey and rat liver, but the specific gene has not been named in the available literature. Related genes include AGXT, TAT, and other transaminases.
What is the reaction catalyzed by GO:0047313?
The reaction is: an aromatic L-alpha-amino acid + glyoxylate = an aromatic oxo-acid + glycine.
What diseases are associated with aromatic-amino-acid:glyoxylate transaminase activity?
It is linked to glyoxylate metabolism and potentially to hyperoxaluria, neurological disorders, and cancer metabolism, though direct evidence is limited.
How can I study aromatic-amino-acid:glyoxylate transaminase activity?
Researchers use enzymatic assays, metabolomics, CRISPR knockout models, and stable isotope tracing to study this activity.
What cofactor does aromatic-amino-acid:glyoxylate transaminase require?
Like most transaminases, it requires pyridoxal 5'-phosphate (PLP) as a cofactor.
Is aromatic-amino-acid:glyoxylate transaminase activity reversible?
Yes, the reaction is reversible, allowing the enzyme to transfer amino groups in both directions depending on substrate availability.
Where is aromatic-amino-acid:glyoxylate transaminase activity found?
It was characterized in monkey and rat liver, but may be present in other tissues.
What is the difference between GO:0047313 and AGXT?
GO:0047313 is a molecular function (transaminase activity), while AGXT is a gene encoding alanine--glyoxylate aminotransferase, which has a different substrate specificity but related glyoxylate metabolism.
How does EDITGENE support research on GO:0047313?
EDITGENE provides CRISPR knockout, point mutation, knock-in, overexpression cell models, and library screening services to study genes related to this activity.
Conclusion
Aromatic-amino-acid:glyoxylate transaminase activity (GO:0047313) is a PLP-dependent molecular function that bridges aromatic amino acid catabolism and glycine/glyoxylate metabolism. First characterized in mammalian liver, this activity contributes to nitrogen disposal, glyoxylate detoxification, and glycine supply, with potential implications for hyperoxaluria, neurological disorders, and cancer metabolism. Despite its metabolic importance, the specific gene(s) encoding this activity remain to be fully defined, offering opportunities for discovery. Modern CRISPR-based models, combined with metabolomics and enzymatic assays, provide powerful tools to dissect its physiological roles and therapeutic potential. EDITGENE stands ready to support these efforts with custom cell models and bioinformatics services.
References
- 1. Harada I et al.. 1978. Purification and characterization of aromatic-amino-acid-glyoxylate aminotransferase from monkey and rat liver.. Hoppe Seylers Z Physiol Chem 359(4):481-8 PMID: 25837
