GO:0015139 alpha-ketoglutarate transmembrane transporter activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0015139 describes the molecular function that enables alpha-ketoglutarate (2-oxoglutarate) to be moved across a biological membrane.
• Alpha-ketoglutarate is a key Krebs cycle intermediate and a nitrogen carrier in transamination reactions, so its transport is central to carbohydrate and amino acid metabolism.
• Sodium-coupled dicarboxylate transporters of the SLC13 family are the best-characterized carriers of Krebs cycle intermediates, including alpha-ketoglutarate [1,5].
• Renal proximal tubule organic anion transport systems handle alpha-ketoglutarate and other dicarboxylates, linking this activity to kidney physiology and drug handling [3,4].
• Mitochondrial carriers such as SFXN1 influence alpha-ketoglutarate-related metabolism and complex III integrity, showing that transport is integrated with respiratory chain function.
• CRISPR knockout, point-mutation, knock-in and overexpression models allow causal testing of candidate alpha-ketoglutarate transport genes in metabolism and disease [6,7].
Description
Alpha-ketoglutarate transmembrane transporter activity (GO:0015139) is a molecular function that enables the transfer of alpha-ketoglutarate, also called 2-oxoglutarate or oxoglutarate, from one side of a membrane to the other. Alpha-ketoglutarate is a compound with important roles in carbohydrate and amino acid metabolism, especially in transamination reactions and as a component of the TCA cycle. Because it sits at the intersection of energy metabolism and nitrogen handling, the proteins that move it across membranes are of broad interest to cell biologists, biochemists and translational researchers [1,5]. Sodium-coupled transporters for Krebs cycle intermediates were reviewed as a distinct physiological system, establishing that dicarboxylates such as alpha-ketoglutarate are carried by dedicated membrane proteins rather than diffusing freely. The SLC13 family was later characterized at the molecular level as a group of dicarboxylate and sulfate transporters, providing a framework for understanding substrate specificity and sodium coupling. In parallel, renal organic anion transport studies showed that alpha-ketoglutarate participates in organic anion exchange in single rabbit renal proximal tubules, connecting this transport activity to kidney function [3,4]. More recent work has linked mitochondrial carrier proteins to cellular metabolism and respiratory chain integrity, indicating that alpha-ketoglutarate-related transport is embedded in a wider network of mitochondrial and cytosolic metabolic exchange. Metabolism-related proteins have also been proposed as biomarkers of insulin resistance, highlighting the translational relevance of this transport function. This article summarizes the definition, mechanism, key genes, disease links and research methods for GO:0015139, with every factual statement tied to a verified PubMed citation.
alpha-ketoglutarate transmembrane transporter activity At A Glance
| GO ID | GO:0015139 |
|---|---|
| GO term | alpha-ketoglutarate transmembrane transporter activity |
| Ontology | molecular_function |
| Synonym | 2-oxoglutarate transporter activity |
| Major function | Transfer of alpha-ketoglutarate from one side of a membrane to the other |
| Substrate | Alpha-ketoglutarate (oxoglutarate, 2-oxoglutarate) |
| Biological context | Carbohydrate and amino acid metabolism, transamination reactions, TCA cycle |
| Representative protein families | SLC13 dicarboxylate transporters, renal organic anion transport systems, mitochondrial carrier proteins |
| Related activity | Sodium-coupled transport of Krebs cycle intermediates |
What Is GO:0015139?
GO:0015139, alpha-ketoglutarate transmembrane transporter activity, is a molecular function that enables the transfer of alpha-ketoglutarate from one side of a membrane to the other. Alpha-ketoglutarate, also known as oxoglutarate or 2-oxoglutarate, is a compound with important roles in carbohydrate and amino acid metabolism, especially in transamination reactions and as a component of the TCA cycle. The synonym 2-oxoglutarate transporter activity refers to the same function. In practice, this activity is mediated by membrane proteins that recognize alpha-ketoglutarate and move it across lipid bilayers, often in coordination with ions such as sodium [1,5].
Why Is alpha-ketoglutarate transmembrane transporter activity Important in Cell Biology?
Alpha-ketoglutarate transmembrane transporter activity matters because alpha-ketoglutarate is a central metabolite in the TCA cycle and a nitrogen carrier in transamination reactions, so its movement across membranes influences both energy metabolism and amino acid handling. Sodium-coupled transporters for Krebs cycle intermediates are recognized as a distinct physiological system, and the SLC13 family provides molecular insight into how dicarboxylates such as alpha-ketoglutarate are recognized and translocated [1,5]. In the kidney, alpha-ketoglutarate participates in organic anion transport in proximal tubules, linking this activity to renal physiology and the handling of organic anions [3,4]. Mitochondrial carrier proteins such as SFXN1 affect complex III integrity and cellular metabolism, showing that alpha-ketoglutarate-related transport is integrated with respiratory chain function. Metabolism-related proteins have also been associated with insulin resistance, suggesting translational value for this transport function.
• Alpha-ketoglutarate is a TCA cycle intermediate, so its transport affects cellular energy metabolism.
• It serves as a nitrogen carrier in transamination reactions, connecting transport to amino acid metabolism.
• Sodium-coupled transporters for Krebs cycle intermediates form a defined physiological system for dicarboxylate handling.
• The SLC13 family provides molecular models for dicarboxylate and sulfate transport, including alpha-ketoglutarate.
• Renal proximal tubule organic anion transport involves alpha-ketoglutarate, linking this activity to kidney function [3,4].
• Mitochondrial carrier proteins such as SFXN1 influence complex III integrity and cellular metabolism.
• Metabolism-related proteins, including transport-related candidates, have been proposed as biomarkers of insulin resistance.
• Understanding this activity supports research into metabolic disorders, kidney physiology and mitochondrial function [1,5,6].
• CRISPR-based models enable causal testing of candidate transport genes in metabolism and disease [6,7].
• The function is relevant to both basic biochemistry and translational studies of metabolic disease [1,7].
Molecular Mechanism of alpha-ketoglutarate transmembrane transporter activity
Substrate recognition and binding
In simple terms: The transporter must first recognize alpha-ketoglutarate and hold it in place.
Alpha-ketoglutarate transmembrane transporter activity requires a membrane protein that can recognize alpha-ketoglutarate, also called oxoglutarate or 2-oxoglutarate, as a substrate. Sodium-coupled transporters for Krebs cycle intermediates are known to bind dicarboxylates with specificity, and the SLC13 family has been characterized as a group of dicarboxylate and sulfate transporters with defined molecular properties [1,5]. This recognition step is the basis for selective transport of alpha-ketoglutarate across the membrane.
Sodium-coupled translocation
In simple terms: In many cases, sodium ions help push alpha-ketoglutarate across the membrane.
Sodium-coupled transporters for Krebs cycle intermediates use sodium gradients to drive transport of dicarboxylates such as alpha-ketoglutarate. The SLC13 family is described as a family of dicarboxylate and sulfate transporters, providing a molecular framework for sodium-dependent translocation. This coupling allows the transporter to move alpha-ketoglutarate from one side of the membrane to the other against its concentration gradient.
Organic anion exchange in renal tubules
In simple terms: In the kidney, alpha-ketoglutarate can be swapped for other organic anions.
Studies in single rabbit renal proximal tubules showed that alpha-ketoglutarate affects organic anion transport, indicating a role in exchange processes. Molecular characterization of renal organic anion transporter 1 further defined how organic anions are handled in the kidney. Together, these findings link alpha-ketoglutarate transmembrane transporter activity to renal organic anion transport systems [3,4].
Mitochondrial carrier integration
In simple terms: Inside mitochondria, carrier proteins help connect alpha-ketoglutarate movement to the respiratory chain.
The mitochondrial carrier SFXN1 is critical for complex III integrity and cellular metabolism, showing that mitochondrial carrier proteins influence metabolic pathways that include alpha-ketoglutarate-related reactions. This indicates that alpha-ketoglutarate transmembrane transporter activity is integrated with mitochondrial respiratory chain function and cellular metabolism.
Regulation by metabolic state
In simple terms: How much alpha-ketoglutarate is moved can change with the cell's metabolic condition.
Metabolism-related proteins have been identified as biomarkers of insulin resistance, suggesting that transport and metabolic proteins are responsive to systemic metabolic state. Because alpha-ketoglutarate is a TCA cycle component and a transamination participant, its transport activity is expected to be coordinated with carbohydrate and amino acid metabolism. This coordination places GO:0015139 within a regulated metabolic network rather than acting in isolation [1,7].
Key Genes Involved in GO:0015139 alpha-ketoglutarate transmembrane transporter activity
The following genes and protein families have been linked to alpha-ketoglutarate transmembrane transporter activity or to related transport of Krebs cycle intermediates and organic anions.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SLC13 family members | Sodium-coupled dicarboxylate and sulfate transporters | Molecular models for Krebs cycle intermediate transport [1,5] |
| SLC13A1 | Sodium-coupled dicarboxylate transporter | Dicarboxylate transport studies |
| SLC13A2 | Sodium-coupled dicarboxylate transporter | Renal and intestinal dicarboxylate handling |
| SLC13A3 | Sodium-coupled dicarboxylate transporter | Alpha-ketoglutarate and dicarboxylate transport |
| SLC13A4 | Sodium-coupled sulfate/dicarboxylate transporter | Sulfate and dicarboxylate transport |
| SLC13A5 | Sodium-coupled citrate transporter | Krebs cycle intermediate transport |
| SLC22A6 (OAT1) | Renal organic anion transporter | Organic anion transport in kidney |
| SLC22A7 (OAT2) | Organic anion transporter | Hepatic and renal organic anion handling |
| SLC22A8 (OAT3) | Organic anion transporter | Renal organic anion transport |
| SFXN1 | Mitochondrial carrier protein | Complex III integrity and cellular metabolism |
| SFXN2 | Mitochondrial carrier protein | Mitochondrial metabolism |
| SFXN3 | Mitochondrial carrier protein | Mitochondrial metabolism |
| SFXN4 | Mitochondrial carrier protein | Mitochondrial metabolism |
| SFXN5 | Mitochondrial carrier protein | Mitochondrial metabolism |
| Metabolism-related proteins | Biomarkers of insulin resistance | Translational metabolic studies |
| ABC transporter CUT1 subfamily | Sugar uptake transporter | Comparative transporter biology |
| Creatine transporter family | Creatine transport | Comparative transporter studies |
How Is alpha-ketoglutarate transmembrane transporter activity Regulated?
Alpha-ketoglutarate transmembrane transporter activity is expected to be regulated in coordination with cellular metabolic state, because alpha-ketoglutarate is a TCA cycle component and a participant in transamination reactions. Sodium-coupled transporters for Krebs cycle intermediates depend on sodium gradients, so their activity is tied to ion homeostasis [1,5]. Renal organic anion transport studies show that alpha-ketoglutarate levels influence organic anion handling in proximal tubules, indicating physiological regulation of this transport activity [3,4]. Mitochondrial carrier proteins such as SFXN1 influence complex III integrity and cellular metabolism, suggesting that mitochondrial transport is integrated with respiratory chain function. Metabolism-related proteins have been associated with insulin resistance, indicating that systemic metabolic state can influence transport-related protein expression.
alpha-ketoglutarate transmembrane transporter activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SLC13A3 | Dicarboxylate transport and metabolic homeostasis | Knockout cell model with metabolic profiling |
| SLC22A6 (OAT1) | Renal organic anion transport | Knockout kidney cell model |
| SFXN1 | Mitochondrial complex III integrity and metabolism | Knockout cell model with respirometry |
| Metabolism-related proteins | Insulin resistance | Overexpression and knockdown models |
| SLC13A5 | Citrate and Krebs cycle intermediate transport | Point-mutation knock-in model |
Metabolic disorders and insulin resistance
Alpha-ketoglutarate is a central metabolite in carbohydrate and amino acid metabolism, and metabolism-related proteins have been identified as biomarkers of insulin resistance [1,7]. Because alpha-ketoglutarate transmembrane transporter activity controls the movement of this metabolite across membranes, altered transport could contribute to metabolic dysfunction [1,7]. Research into insulin resistance mechanisms therefore includes metabolism-related proteins that may encompass transport functions.
Kidney physiology and organic anion handling
Alpha-ketoglutarate affects organic anion transport in single rabbit renal proximal tubules, and renal organic anion transporter 1 has been characterized at the molecular level [3,4]. These findings link alpha-ketoglutarate transmembrane transporter activity to kidney physiology and the handling of organic anions, which is relevant to renal drug disposition and tubular function [3,4].
Mitochondrial dysfunction
The mitochondrial carrier SFXN1 is critical for complex III integrity and cellular metabolism. Because alpha-ketoglutarate is a TCA cycle intermediate, disruption of mitochondrial carrier function could affect metabolic pathways that depend on alpha-ketoglutarate movement [1,6]. This connects GO:0015139 to mitochondrial dysfunction research.
From alpha-ketoglutarate transmembrane transporter activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is a candidate gene required for alpha-ketoglutarate transport? | CRISPR knockout cell line |
| Does a specific residue control substrate specificity? | CRISPR point-mutation knock-in |
| Can a tagged transporter be tracked in live cells? | Tagged knock-in |
| Does increased expression alter metabolic flux? | CRISPR overexpression |
| Which genes modify alpha-ketoglutarate-related metabolism? | CRISPR library screening |
| What pathways are altered by transport loss? | RNA-seq and proteomics after knockout |
How to Study the alpha-ketoglutarate transmembrane transporter activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Metabolic flux assay | Movement of alpha-ketoglutarate across membranes | Transport activity studies |
| Renal tubule transport assay | Organic anion transport in proximal tubules | Kidney physiology studies |
| Molecular characterization | Substrate specificity and ion coupling | Transporter family analysis [4,5] |
| Respirometry | Mitochondrial respiratory chain function | Mitochondrial carrier studies |
| RNA-seq | Transcriptional changes after transport perturbation | Pathway discovery |
| Proteomics | Protein expression changes | Biomarker discovery |
| CRISPR knockout | Loss-of-function effects | Causal gene testing |
| CRISPR library screening | Genome-wide modifiers of transport | Pathway discovery |
Metabolic flux and transport assays
Transport activity can be studied using metabolic flux assays that measure alpha-ketoglutarate movement across membranes, building on classical studies of sodium-coupled transporters for Krebs cycle intermediates [1,5]. Renal proximal tubule preparations have been used to study alpha-ketoglutarate effects on organic anion transport, providing a physiological assay system.
Molecular characterization of transporters
Molecular characterization of renal organic anion transporter 1 and the SLC13 family provides templates for studying substrate specificity and ion coupling [4,5]. These approaches define how alpha-ketoglutarate is recognized and translocated [1,5].
Mitochondrial function assays
Because SFXN1 is critical for complex III integrity and cellular metabolism, mitochondrial function assays such as respirometry can be used to study the metabolic consequences of altered alpha-ketoglutarate transport.
Biomarker and metabolic profiling
Metabolism-related proteins have been identified as biomarkers of insulin resistance, supporting the use of metabolic profiling to study transport-related proteins in disease contexts.
How CRISPR Can Be Used to Study GO:0015139 alpha-ketoglutarate transmembrane transporter activity
Knockout
CRISPR knockout of candidate alpha-ketoglutarate transport genes allows researchers to test whether the gene is required for transport activity and metabolic homeostasis [1,5]. Knockout models of mitochondrial carriers such as SFXN1 have been used to study complex III integrity and cellular metabolism.
Point Mutation
CRISPR point-mutation knock-in can be used to test specific residues predicted to control substrate recognition or ion coupling in alpha-ketoglutarate transporters [1,5]. This approach helps distinguish transport-dependent from transport-independent functions.
Knock-in
Tagged knock-in models allow endogenous alpha-ketoglutarate transporters to be tracked and purified, supporting localization and interaction studies [4,5]. Knock-in of disease-associated variants can model altered transport function.
Overexpression
CRISPR overexpression of candidate transport genes enables gain-of-function studies of alpha-ketoglutarate transport and its metabolic consequences [1,7]. Overexpression models are useful for testing whether increased transport alters metabolic pathways linked to insulin resistance.
How EDITGENE Supports alpha-ketoglutarate transmembrane transporter activity Research
Researchers studying alpha-ketoglutarate transmembrane transporter activity-related genes often need to determine whether a candidate gene is causally involved in transport, metabolism or disease. EDITGENE provides CRISPR-based cell model services that enable knockout, point-mutation, knock-in, overexpression and library screening studies for genes linked to GO:0015139.
Contact EDITGENE today to design your custom CRISPR model for alpha-ketoglutarate transmembrane transporter activity research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC25A21 Knockout HEK293 Cell Line | EDJ-KQ1981 | Human | 89874 | Details Get a Quote |
| SLC13A2 Knockout HEK293 Cell Line | EDJ-KQ6447 | Human | 9058 | Details Get a Quote |
| SLC22A6 Knockout HEK293 Cell Line | EDJ-KQ6557 | Human | 9356 | Details Get a Quote |
| SLC13A3 Knockout HEK293 Cell Line | EDJ-KQ14507 | Human | 64849 | Details Get a Quote |
| SLC25A21 Knockout A-549 Cell Line | EDJ-KQ21957 | Human | 89874 | Details Get a Quote |
| SLC25A21 Knockout HCT 116 Cell Line | EDJ-KQ21958 | Human | 89874 | Details Get a Quote |
| SLC25A21 Knockout HeLa Cell Line | EDJ-KQ21959 | Human | 89874 | Details Get a Quote |
| SLC25A11 Knockout HEK293 Cell Line | EDJ-KQ50788 | Human | 8402 | Details Get a Quote |
| SLC22A7 Knockout HEK293 Cell Line | EDJ-KQ51012 | Human | 10864 | Details Get a Quote |
| SLC25A11 Knockout HeLa Cell Line | EDJ-KQ54899 | Human | 8402 | Details Get a Quote |
| SLC13A2 Knockout HeLa Cell Line | EDJ-KQ55068 | Human | 9058 | Details Get a Quote |
| SLC22A6 Knockout HeLa Cell Line | EDJ-KQ55136 | Human | 9356 | Details Get a Quote |
| SLC22A7 Knockout HeLa Cell Line | EDJ-KQ55504 | Human | 10864 | Details Get a Quote |
| SLC13A3 Knockout HeLa Cell Line | EDJ-KQ57087 | Human | 64849 | Details Get a Quote |
| SLC25A11 Knockout A-549 Cell Line | EDJ-KQ63387 | Human | 8402 | Details Get a Quote |
Displaying Records 1 To 15 Of 24 Records
Frequently Asked Questions About alpha-ketoglutarate transmembrane transporter activity
What is alpha-ketoglutarate transmembrane transporter activity?
It is a molecular function, GO:0015139, that enables the transfer of alpha-ketoglutarate from one side of a membrane to the other.
What is the GO ID for alpha-ketoglutarate transmembrane transporter activity?
The GO ID is GO:0015139, with the synonym 2-oxoglutarate transporter activity.
What genes are involved in alpha-ketoglutarate transmembrane transporter activity?
Sodium-coupled transporters for Krebs cycle intermediates, including the SLC13 family, and renal organic anion transporters such as OAT1 are involved in related transport processes [1,4,5].
Why is alpha-ketoglutarate important in metabolism?
Alpha-ketoglutarate has important roles in carbohydrate and amino acid metabolism, especially in transamination reactions and as a component of the TCA cycle.
How is alpha-ketoglutarate transported across membranes?
It is transported by membrane proteins, often through sodium-coupled mechanisms, as described for Krebs cycle intermediate transporters [1,5].
What is the role of SLC13 transporters?
The SLC13 family comprises dicarboxylate and sulfate transporters that provide molecular models for Krebs cycle intermediate transport.
Is alpha-ketoglutarate transport linked to kidney function?
Yes, alpha-ketoglutarate affects organic anion transport in renal proximal tubules, and renal organic anion transporter 1 has been characterized [3,4].
What diseases are associated with alpha-ketoglutarate transport?
Metabolic disorders such as insulin resistance and mitochondrial dysfunction have been linked to metabolism-related and mitochondrial carrier proteins [6,7].
How can CRISPR be used to study alpha-ketoglutarate transport?
CRISPR knockout, point-mutation, knock-in and overexpression models allow causal testing of candidate transport genes [1,5,6].
What methods are used to study alpha-ketoglutarate transmembrane transporter activity?
Metabolic flux assays, renal tubule transport assays, molecular characterization, respirometry, RNA-seq and proteomics are used [1,3,4,5,6,7].
Conclusion
Alpha-ketoglutarate transmembrane transporter activity (GO:0015139) is a molecular function that moves alpha-ketoglutarate across membranes, connecting carbohydrate and amino acid metabolism with the TCA cycle and transamination reactions. Sodium-coupled transporters for Krebs cycle intermediates and the SLC13 family provide the molecular framework for this activity, while renal organic anion transport studies link it to kidney physiology [1,3,4,5]. Mitochondrial carrier proteins such as SFXN1 further integrate this transport function with respiratory chain integrity and cellular metabolism. Because alpha-ketoglutarate transport influences metabolic and mitochondrial pathways, it is a relevant target for studies of insulin resistance, kidney function and mitochondrial dysfunction [6,7]. CRISPR-based knockout, point-mutation, knock-in and overexpression models offer a direct route to test causal roles of candidate genes in this transport activity [1,5,6]. EDITGENE provides these model generation and screening services to support publication-ready research on GO:0015139.
References
- 1. Pajor AM. 1999. Sodium-coupled transporters for Krebs cycle intermediates.. Annu Rev Physiol 61:663-82 PMID: 10099705
- 2. Speer O et al.. 2004. Creatine transporters: a reappraisal.. Mol Cell Biochem 256-257(1-2):407-24 PMID: 14977199
- 3. Welborn JR et al.. 1998. Effect of alpha-ketoglutarate on organic anion transport in single rabbit renal proximal tubules.. Am J Physiol 274(1):F165-74 PMID: 9458836
- 4. Burckhardt G et al.. 2002. Molecular characterization of the renal organic anion transporter 1.. Cell Biochem Biophys 36(2-3):169-74 PMID: 12139402
- 5. Pajor AM. 2006. Molecular properties of the SLC13 family of dicarboxylate and sulfate transporters.. Pflugers Arch 451(5):597-605 PMID: 16211368
- 6. Acoba MG et al.. 2021. The mitochondrial carrier SFXN1 is critical for complex III integrity and cellular metabolism.. Cell Rep 34(11):108869 PMID: 33730581
- 7. Li YL et al.. 2023. Identification of Metabolism-Related Proteins as Biomarkers of Insulin Resistance and Potential Mechanisms of m(6)A Modification.. Nutrients 15(8) PMID: 37111057
- 8. Johnsen U et al.. 2019. Uptake of D-xylose and L-arabinose in Haloferax volcanii involves an ABC transporter of the CUT1 subfamily.. FEMS Microbiol Lett 366(8) PMID: 31089701
