@article{2895,
  keywords = {Animals, Mice, Humans, Substrate Specificity, Mice, Inbred C57BL, Male, Mice, Knockout, Isoenzymes, Metabolomics, Testis, DNA Methylation, Glutarates, L-Lactate Dehydrogenase},
  author = {Xin Teng and Matthew Emmett and Mitchell Lazar and Erwin Goldberg and Joshua Rabinowitz},
  title = {Lactate Dehydrogenase C Produces S-2-Hydroxyglutarate in Mouse Testis.},
  abstract = { <p>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.</p> },
  year = {2016},
  journal = {ACS Chem Biol},
  volume = {11},
  pages = {2420-7},
  month = {2016 Sep 16},
  issn = {1554-8937},
  doi = {10.1021/acschembio.6b00290},
  language = {eng},
}