ArticleACS chemical biology2016
Lactate Dehydrogenase C Produces S-2-Hydroxyglutarate in Mouse Testis.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- LDH isozymes as targets for cancer therapy.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Article
- Generation and Characterization of a Genetically ModifiedInternational journal of molecular sciences · 2026Article
- L-2-hydroxyglutarate regulates centromere and heterochromatin conformation in the male germline.PLoS genetics · 2025Article
- Pyruvate modulation of redox potential controls mouse sperm motility.Developmental cell · 2024Article
- Cytosolic and mitochondrial NADPH fluxes are independently regulated.Nature chemical biology · 2023Article
- Basic Mechanisms of Immunometabolites in Shaping the Immune Response.Journal of innate immunity · 2023Review
- NMR-based isotope editing, chemoselection and isotopomer distribution analysis in stable isotope resolved metabolomics.Methods (San Diego, Calif.) · 2022Review
- Resolving Enantiomers of 2-Hydroxy Acids by Nuclear Magnetic Resonance.Analytical chemistry · 2022Article
- Effect of Electroacupuncture at Wushu Acupoints of the Cardiopulmonary Meridian on the Autophagy in Rats with Acute Myocardial Ischemia.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Synthesis of [1-NMR in biomedicine · 2021Article
- Mitochondria as Signaling Organelles Control Mammalian Stem Cell Fate.Cell stem cell · 2021Review
- The oncometabolite L-2-hydroxyglutarate is a common product of dipteran larval development.Insect biochemistry and molecular biology · 2020Article
- Teleological role of L-2-hydroxyglutarate dehydrogenase in the kidney.Disease models & mechanisms · 2020Article
- Present and Future of Anti-Glioblastoma Therapies: A Deep Look into Molecular Dependencies/Features.Molecules (Basel, Switzerland) · 2020Review
- Dysregulation of 2-oxoglutarate-dependent dioxygenases by hyperglycaemia: does this link diabetes and vascular disease?Clinical epigenetics · 2020Review
- Mitochondrial TCA cycle metabolites control physiology and disease.Nature communications · 2020Review
- 2-Hydroxyglutarate Metabolism Is Altered in anFrontiers in physiology · 2020Article
- Article
- Quantification of D- and L-2-Hydroxyglutarate in Drosophila melanogaster Tissue Samples Using Gas Chromatography-Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Metabolomics is a valuable tool for studying tissue- and organism-specific metabolism. In normal mouse testis, we found 70 μM S-2-hydroxyglutarate (2HG), more than 10-fold greater than in other tissues. S-2HG is a competitive inhibitor of α-ketoglutarate-dependent demethylation enzymes and can alter histone or DNA methylation. To identify the source of testis S-2HG, we fractionated testis extracts and identified the fractions that actively produced S-2HG. Through a combination of ion exchange and size exclusion chromatography, we enriched a single active protein, the lactate dehydrogenase isozyme LDHC, which is primarily expressed in testis. At neutral pH, recombinant mouse LDHC rapidly converted both pyruvate into lactate and α-ketoglutarate into S-2HG, whereas recombinant human LDHC only produced lactate. Rapid S-2HG production by LDHC depends on amino acids 100-102 being Met-Val-Ser, a sequence that occurs only in the rodent protein. Other mammalian LDH can also produce some S-2HG, but at acidic pH. Thus, polymorphisms in the Ldhc gene control testis levels of S-2HG, and thereby epigenetics, across mammals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.