Non-enzymatic chemistry enables 2-hydroxyglutarate-mediated activation of 2-oxoglutarate oxygenases
Open accessAbstract
Accumulation of (R)-2-hydroxyglutarate in cells results from mutations to isocitrate dehydrogenase that correlate with cancer. A recent study reports that (R)-, but not (S)-2-hydroxyglutarate, acts as a co-substrate for the hypoxia-inducible factor prolyl hydroxylases via enzyme-catalysed oxidation to 2-oxoglutarate. Here we investigate the mechanism of 2-hydroxyglutarate-enabled activation of 2-oxoglutarate oxygenases, including prolyl hydroxylase domain 2, the most important human prolyl hydroxylase isoform. We observe that 2-hydroxyglutarate-enabled catalysis by prolyl hydroxylase domain 2 is not enantiomer-specific and is stimulated by ferrous/ferric ion and reducing agents including L-ascorbate. The results reveal that 2-hydroxyglutarate is oxidized to 2-oxoglutarate non-enzymatically, likely via iron-mediated Fenton-chemistry, at levels supporting in vitro catalysis by 2-oxoglutarate oxygenases. Succinic semialdehyde and succinate are also identified as products of 2-hydroxyglutarate oxidation. Overall, the results rationalize the reported effects of 2-hydroxyglutarate on catalysis by prolyl hydroxylases in vitro and suggest that non-enzymatic 2-hydroxyglutarate oxidation may be of biological interest.
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High levels of succinate or 2-HG inhibit α-KGDDs, including PHDs, TET DNA demethylases, and JMJDs.
“High levels of succinate or 2-HG inhibit α-KGDDs. These include the PHDs, the TET DNA demethylases, and the JMJDs154-156”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [155]
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“…accumulated in both OGDH and LIAS KO clones compared to the controls was 2-hydroxyglutarate (2-HG) (Figures 5A and 5B), a chiral compound derived from 2-OG (Figures 5C and 5D) that can inhibit 2-OG dioxygenases (Chowdhury et al., 2011; Koivunen et al., 2012; Tarhonskaya et al., 2014b).”
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“This phenotype is thought to result from increased EglN activity fueled by 2HG-αKG isomerization (Tarhonskaya et al., 2014).”
BackgroundThe Roles of 2-Hydroxyglutarate
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Morin, A., Letouzé, É., Gimenez‐Roqueplo, A., & Favier, J. (2014) · International Journal of Cancer · doi:10.1002/ijc.29080 · Cited by 150 · see citing works
“challenged these data by showing that the nonenzymatic in vitro conversion of 2-HG to 2-OG may actually had occurred, leading to misinterpretation of these results.(39) Further work will thus be needed to precisely understand the exact impact of (R)2-HG on PHD activity.”
BackgroundBardella, C., Al‐Dalahmah, O., Krell, D., Brazauskas, P., Al‐Qahtani, K., Tomková, M., Adam, J., Serres, S., Lockstone, H. E., Freeman-Mills, L., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.08.017 · Cited by 150 · see citing works
“, 2011), and prolyl hydroxylases (PHDs) that have targets such as HIF1a and collagen (Borger et al., 2012; Chowdhury et al., 2011; Duncan et al., 2012; Figueroa et al., 2010; Hirata et al., 2015; Lu et al., 2012; Sasaki et al., 2012b; Tarhonskaya et al., 2014; Xu et al., 2011).”
BackgroundSelf-citationOncogenic Activities of IDH1/2 Mutations: From Epigenetics to Cellular Signaling
Gagné, L. M., Boulay, K., Topisirović, I., Huot, M., & Mallette, F. A. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.06.002 · Cited by 141 · see citing works
2-Hydroxyglutarate in Cancer Cells
Ježek, P. (2020) · Antioxidants & Redox Signaling · doi:10.1089/ars.2019.7902 · Cited by 130 · see citing works
De novo pyrimidine synthesis is a targetable vulnerability in IDH mutant glioma
Shi, D. D., Savani, M. R., Levitt, M. M., Wang, A. C., Endress, J. E., Bird, C. E., Buehler, J., Stopka, S. A., Regan, M. S., Lin, Y., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.07.011 · Cited by 135 · see citing works
“(R)-2HG also stimulates the EglN1 prolyl hydroxylase, a 2OG-dependent dioxygenase that promotes degradation of the hypoxia-inducible factor 1 alpha transcription factor (Koivunen et al., 2012; Tarhonskaya et al., 2014).”
BackgroundVitamin C in Stem Cell Biology: Impact on Extracellular Matrix Homeostasis and Epigenetics
D’Aniello, C., Cermola, F., Patriarca, E. J., & Minchiotti, G. (2017) · Stem Cells International · doi:10.1155/2017/8936156 · Cited by 132 · see citing works
“Moreover, it has recently been reported that VitC stimulates the iron-mediated nonenzymatic conversion of the oncometabolite α-hydroxyglutarate (2-HG) into αketoglutarate [41].”
BackgroundPharmacological targeting of the HIF hydroxylases – A new field in medicine development
Chan, M. C., Holt‐Martyn, J. P., Schofield, C. J., & Ratcliffe, P. J. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.01.001 · Cited by 126 · see citing works
Self-citationTarhonskaya, H., Hardy, A., Howe, E. A., Loik, N. D., Kramer, H., McCullagh, J., Schofield, C. J., & Flashman, E. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.653014 · Cited by 91 · see citing works
“Enzyme Activity Assays and Studies of O2 Dependence— Enzymatic assays were conducted as described (46, 47).”
MethodSelf-citationHollinshead, K. E. R., Munford, H., Eales, K. L., Bardella, C., Li, C., Escribano-Gonzalez, C., Thakker, A., Nonnenmacher, Y., Kľučková, K., Jeeves, M., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.084 · Cited by 88 · see citing works
“It is important to note that the 2HG produced by mutant IDH1 may interfere with cell survival and proliferation in hypoxia by inhibiting the stabilization of the transcription factor, hypoxia inducible factor 1 (HIF1) (Koivunen et al., 2012; Tarhonskaya et al., 2014).”
Sadiku, P., Willson, J. A., Dickinson, R. S., Murphy, F. A., Harris, A. J., Lewis, A., Sammut, D., Mirchandani, A. S., Ryan, E. M., Watts, E., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90848 · Cited by 86 · see citing works
Self-citationOH, the Places You’ll Go! Hydroxylation, Gene Expression, and Cancer
Ploumakis, A., & Coleman, M. L. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.05.026 · Cited by 74 · see citing works
“The ability of D-2HG to stimulate the in vitro activity of PHDs results from its non-enzymatic conversion into 2OG (Tarhonskaya et al., 2014).”
BackgroundHeart failure—emerging roles for the mitochondrial pyruvate carrier
Fernández-Caggiano, M., & Eaton, P. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-020-00729-0 · Cited by 70 · see citing works
“[61], which otherwise hydroxylates two conserved prolines in HIF-1 resulting in its ubiquitin-dependent proteosomal degradation.”
BackgroundIsocitrate dehydrogenase variants in cancer — Cellular consequences and therapeutic opportunities
Liu, S., Cadoux-Hudson, T. A. D., & Schofield, C. J. (2020) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2020.06.012 · Cited by 70 · see citing works
Self-citationMetabolic implications of hypoxia and pseudohypoxia in pheochromocytoma and paraganglioma
Kľučková, K., & Tennant, D. A. (2018) · Cell and Tissue Research · doi:10.1007/s00441-018-2801-6 · Cited by 66 · see citing works
“2016), although this may be through non-enzymatic oxidation to 2OG (Tarhonskaya et al. 2014).”
BackgroundThe small members of the JMJD protein family: Enzymatic jewels or jinxes?
Oh, S., Shin, S., & Janknecht, R. (2019) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2019.04.002 · Cited by 60 · see citing works
Hypoxic Signalling in Tumour Stroma
Laitala, A., & Erler, J. T. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00189 · Cited by 54 · see citing works
“However, the mechanisms for the PHD activation by 2-HG is debated (53).”
BackgroundPhotoredox systems with biocatalysts for CO 2 utilization
Amao, Y. (2018) · Sustainable Energy & Fuels · doi:10.1039/c8se00209f · Cited by 49 · see citing works
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“A a critical intermediate in tricarboxylic acid cycle (TCA cycle), 2-ketoglutarate (2-KG) can be converted into succinylCoA (1), succinate (2), L-glutamate (3), or 2-hydroxyglutarate (2HG) (4).”
BackgroundMolecular markers of paragangliomas/pheochromocytomas
Zhikrivetskaya, S. O., Snezhkina, A. V., Zaretsky, A. R., Alekseev, B. Y., Pokrovsky, A. V., Golovyuk, A. L., Melnikova, N. V., Stepanov, O. A., Kalinin, D. V., Moskalev, A., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.15201 · Cited by 43 · see citing works
“Alternatively, a more recent study demonstrated the possibility of nonenzymatic conversion of 2-hydroxyglutarate to 2-oxoglutarate, indicating that the earlier results may have been misinterpreted [133].”
ResultCasalino‐Matsuda, S. M., Wang, N., Ruhoff, P. T., Matsuda, H., Nlend, M., Nair, A., Szleifer, I. G., Beitel, G. J., Sznajder, J. I., & Sporn, P. H. S. (2018) · Scientific Reports · doi:10.1038/s41598-018-32008-x · Cited by 43 · see citing works
“Genes downregulated by elevated CO 2 included gamma-butyretaine hydroxlase 1 (BBOX 1), which catalyzes synthesis of L-carnitine, an essential co-factor in beta-oxidation 55 ; kynurenine 3-monooxygenase (KMO), an outer mitochondrial membrane protein that hydroxylates tryptophan to form kynurenine 56 ; BCL2 interacting…”
BackgroundBailey, P. S. J., & Nathan, J. A. (2018) · Biomedicines · doi:10.3390/biomedicines6020060 · Cited by 41 · see citing works
“[52] showed that in vitro activity of PHD2 can be activated by D-2-HG, in an iron and ascorbate dependent mechanism, where endogenous 2-OG is reoxidised from D-2-HG via a non-enzymatic Fenton reaction with the active site iron.”
BackgroundIdentification of Circulating Genomic and Metabolic Biomarkers in Intrahepatic Cholangiocarcinoma
Winter, H., Kaisaki, P. J., Harvey, J., Giacopuzzi, E., Ferla, M. P., Pentony, M. M., Knight, S. J. L., Sharma, R. A., Taylor, J. C., & McCullagh, J. (2019) · Cancers · doi:10.3390/cancers11121895 · Cited by 38 · see citing works
Self-citationZhang, M., Cheng, S.-T., Wang, H., Wu, J., Luo, Y., Wang, Q., Wang, F., & Xia, G. (2016) · Journal of Proteomics · doi:10.1016/j.jprot.2016.11.011 · Cited by 37 · see citing works
Nonenzymatic Reactions in Natural Product Formation
Bouthillette, L. M., Aniebok, V., Colosimo, D. A., Brumley, D., & MacMillan, J. B. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.2c00306 · Cited by 37 · see citing works
Armitage, E. G., Kotze, H. L., Allwood, J. W., Dunn, W. B., Goodacre, R., & Williams, K. J. (2015) · Scientific Reports · doi:10.1038/srep15649 · Cited by 34 · see citing works
Macklin, P. S., Yamamoto, A., Browning, L., Hofer, M., Adam, J., & Pugh, C. W. (2020) · The Journal of Pathology · doi:10.1002/path.5402 · Cited by 33 · see citing works
“However, D-2-HG is a relatively poor inhibitor of PHDs as compared to other dioxygenases [110–112] and can be easily oxidised back to 2-OG [113].”
BackgroundCrispo, F., Pietrafesa, M., Condelli, V., Maddalena, F., Bruno, G., Piscazzi, A., Sgambato, A., Esposito, F., & Landriscina, M. (2020) · Molecules · doi:10.3390/molecules25163754 · Cited by 32 · see citing works
“In a reducing environment and at physiologically relevant concentrations of Fe (II/III), the apparent activation of PHD2 by d-2HG is caused by a non-enzymatic conversion of 2-HG to α-KG [98].”
BackgroundEnigmas of IDH mutations in hematology/oncology
Heuser, M., Cruz, M. M. A., Goparaju, R., & Chaturvedi, A. (2015) · Experimental Hematology · doi:10.1016/j.exphem.2015.05.005 · Cited by 28 · see citing works
Isocitrate dehydrogenase gene variants in cancer and their clinical significance
Cadoux-Hudson, T. A. D., Schofield, C. J., & McCullagh, J. (2021) · Biochemical Society Transactions · doi:10.1042/bst20210277 · Cited by 27 · see citing works
Self-citationOncometabolite 2-hydroxyglutarate regulates anti-tumor immunity
Cai, M., Zhao, J., Ding, Q., & Wei, J. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e24454 · Cited by 26 · see citing works
Genetically Modeled Mice with Mutations in Mitochondrial Metabolic Enzymes for the Study of Cancer
Piruat, J. I., & Millán‐Uclés, Á. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00200 · Cited by 21 · see citing works
“Quite the opposite, 2-HG is able to activate PHD2 by prior non-enzymatic oxidation to α-KG (83, 84).”
BackgroundInhibitors of both the N -methyl lysyl- and arginyl-demethylase activities of the JmjC oxygenases
Bonnici, J., Tumber, A., Kawamura, A., & Schofield, C. J. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2017.0071 · Cited by 23 · see citing works
“Certain TCA cycle metabolites inhibit 2OG oxygenases, including the JmjC KDMs with varying potencies [37,39, 43,44].”
Self-citationMitochondrial metabolic remodeling in response to genetic and environmental perturbations
Hollinshead, K. E. R., & Tennant, D. A. (2016) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1334 · Cited by 21 · see citing works
“It has been suggested to be through direct use of only the (R) enantiomer by the PHDs as a substrate(109,111) or through nonenzymatic oxidation of 2HG into αKG, therefore acting as a source of the normal substrate.(112) Consistent with either mechanism, IDH mutant cells display decreased HIF activation compared with t…”
BackgroundGlutamate dehydrogenase1 supports HIF‐1α stability to promote colorectal tumorigenesis under hypoxia
Hu, K., Ding, Y., Zhu, H., Jing, X., He, W., Yu, H. T., & Wang, X. (2023) · The EMBO Journal · doi:10.15252/embj.2022112675 · Cited by 19 · see citing works
“Also, a prolyl hydroxylases in vitro assay showed 2- Hydroxyglutarate (2HG) could activate EGLN1 (Tarhonskaya et al, 2014) probably because 2HG has a similar structure with aKG and meanwhile in vitro assay facilitated the enriched 2HG to bind EGLN1.”
BackgroundLi, Z., Zhen, S., Su, K., Tumber, A., Yu, Q., Dong, Y., McDonough, M. A., Schofield, C. J., & Zhang, X. (2020) · Chemical Communications · doi:10.1039/d0cc06353c · Cited by 19 · see citing works
Self-citationFaqiang, Z., Niu, M., Guo, K.-K., Ma, Y., Fu, Q., Liu, Y., Feng, Z., Mi, W., & Wang, L. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02537-4 · Cited by 19 · see citing works
“However, in the context of hypoxia and mitochondrial deficit, glutamine is the major source of S-2HG with lower glucose and oxygen consumption [40].”
BackgroundDeciphering the multifaceted roles and clinical implications of 2-hydroxyglutarate in cancer
Hao, J., Huang, Z., Zhang, S., Song, K., Wang, J., Gao, C., Fang, Z., & Zhang, N. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107437 · Cited by 15 · see citing works
Dai, W., Li, Y., Sun, W., Ji, M., Bao, R., Chen, J., Xu, S., Dai, Y., Chen, Y., Liu, W., et al. (2022) · Cancer Science · doi:10.1111/cas.15540 · Cited by 14 · see citing works
van Lith, S. A. M., Navis, A. C., Lenting, K., Verrijp, K. N., Schepens, J. T. G., Hendriks, W. J. A. J., Schubert, N. A., Venselaar, H., Wevers, R. A., van Rooij, A., et al. (2016) · Scientific Reports · doi:10.1038/srep30486 · Cited by 14 · see citing works
“Although this has been matter of debate, consensus is now that D-2-HG can promote degradation of the transcription factor hypoxia-inducible factor (HIF-1 α ), possibly after non-enzymatic oxidation to α -KG 14 .”
Effects of hypoxia/hypercapnia on the metablism of Callosobruchus chinensis (L.) larvae
Cui, S., Wang, L., Qiu, J. P., Geng, X., & Liu, Z. C. (2019) · Journal of Stored Products Research · doi:10.1016/j.jspr.2019.06.002 · Cited by 13 · see citing works
Belle, R., Saraç, H., Salah, E., Bhushan, B., Szykowska, A., Roper, G., Tumber, A., Kriaučionis, S., Burgess-Brown, N., Schofield, C. J., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c01820 · Cited by 13 · see citing works
Self-citationQuaye, J. A., & Gadda, G. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.103007 · Cited by 11 · see citing works
“In a study on mitochondrial 2oxoglutarate oxygenase, inhibition of the glutathionemediated 2-hydroxyglutarate oxidation is observed when the essential Fe or Fe is substituted with Zn, Ni, Cu, Mn, or Co (32).”
BackgroundThe Crucial Roles of Intermediate Metabolites in Cancer
Huang, S., Wang, Z., & Zhao, L. (2021) · Cancer Management and Research · doi:10.2147/cmar.s321433 · Cited by 11 · see citing works
“PHD, which is involved in the hydroxylation of HIF1α, was the first dioxygenase reported to be inhibited by 2-HG (MeSr mode).(61,62) The inhibition of hydroxylation leads to HIF-1α stabilization and the subsequent activation of genes containing HIF response elements (HREs), such as glycolytic enzymes, further contribu…”
BackgroundQuaye, J. A., & Gadda, G. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.103008 · Cited by 10 · see citing works
Peng, S., Chen, H., Chen, L., Yang, G., Liu, J., Cheng, X., & Tang, Y. (2022) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.1c00254 · Cited by 10 · see citing works
Preclinical modeling of lower-grade gliomas
Tang, L. W., Mallela, A. N., Deng, H., Richardson, T. E., Hervey‐Jumper, S. L., McBrayer, S. K., & Abdullah, K. G. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1139383 · Cited by 8 · see citing works
“However, HIF1a also exerts tumor suppressive effects in glial cells (8), and (R)-2HG has been shown to stimulate HIF1a degradation as part of the oncogenic program associated with IDH mutations in glioma (9, 10).”
BackgroundResolving Enantiomers of 2-Hydroxy Acids by Nuclear Magnetic Resonance
Lin, P., Crooks, D. R., Linehan, W. M., Fan, T. W. ‐., & Lane, A. N. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.2c00490 · Cited by 7 · see citing works
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“Fe(III).2OG complexes, it will be of interest to test whether known OGO inhibitor classes, including oncometabolites such as (2 R )-hydroxyglutarate 79–81 bind to, or even react with, OGO.”
BackgroundSelf-citationGenetic approaches to understand cellular responses to oxygen availability
Ortmann, B. M., & Nathan, J. A. (2021) · FEBS Journal · doi:10.1111/febs.16072 · Cited by 6 · see citing works
Long, Y., Xu, J., Xu, Z., Su, Z., Li, W., & Li, J. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.119692 · Cited by 3 · see citing works
2-Oxoglutarate-dependent dioxygenases as oxygen sensors: their importance in health and disease
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Biophysical investigation of metal-substituted D-2-hydroxyglutarate dehydrogenase
Moni, B. M., Quaye, J. A., & Gadda, G. (2025) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2025.110397 · Cited by 3 · see citing works
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The return of quiescence metabolites
Coller, H. A. (2021) · Nature Cell Biology · doi:10.1038/s41556-021-00640-x · Cited by 2 · see citing works
A bacterial enzyme may correct 2-HG accumulation in human cancers
Yin, W. J. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1235191 · Cited by 1 · see citing works
“The non-enzymatic oxidation of 2-HG to a-KG may contribute to such an activation effect (10).”
BackgroundThe role of cytosine modification symmetry in mammalian epigenome regulation
Cakil, Z. V., Engelhard, L., & Summerer, D. (2025) · Chemical Science · doi:10.1039/d5sc09022a · Cited by 1 · see citing works
Heart Failure - Emerging Roles for the Mitochondrial Pyruvate Carrier
Fernández-Caggiano, M. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.10.285 · Cited by 1 · see citing works
Zhang, F., Niu, M., Guo, K., Ma, Y., Fu, Q., Liu, Y., Feng, Z., Mi, W., & Wang, L. (2022) · Figshare · doi:10.6084/m9.figshare.20267414
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- Authors
- Tarhonskaya, H., Rydzik, A. M., Leung, I. K. H., Loik, N. D., Chan, M. C., Kawamura, A., McCullagh, J. S. O., Claridge, T. D. W., Flashman, E., & Schofield, C. J.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Flashman, Emily
- Schofield, Christopher J.
- ORCID
- Venue
- Nature Communications
- Published
- 2014-03-05
- Volume
- 5
- Issue
- 1
- Pages
- 3423-3423
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC3959194
- OpenAlex
- W2074128267
- Cited by
- 80
- References
- 59
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 9 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 10 · 2017: 8 · 2016: 9 · 2015: 6 · 2014: 5
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Wellcome Trust
- Cancer Research UK (18245)
- British Heart Foundation (PG/12/33/29546)
- University of Oxford
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- Topics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Keywords
- 2-hydroxyglutarate, prolyl hydroxylase domain 2, non-enzymatic oxidation, Fenton chemistry, iron-mediated oxidation, IDH mutation, succinic semialdehyde, succinic acid, L-ascorbate, cancer metabolism, enantiomer specificity
- MeSH terms
- Alcohol Oxidoreductases, Ascorbic Acid, gamma-Aminobutyric Acid, Glutarates, Oxygenases, Succinic Acid
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