Membrane-permeant precursor form of the oncometabolite L-2-hydroxyglutarate that inhibits α-ketoglutarate/α-KG-dependent dioxygenases.
Octyl-(S)-2HG (Octyl-L-2HG) is a membrane-permeant precursor form of the oncometabolite L-2-hydroxyglutarate (L2HG) produced from α‐KG by malate dehydrogenases (MDH1/2) and lactate dehydrogenase (LDHA). L2HG can be converted back to α-KG by L-2-hydroxyglutarate dehydrogenase (LHGDH), deletion or mutations of which lead to L2HG accumulation, metabolic disorders and reduced 5hmC levels. Both D- and L-2HG inhibit Jumonji histone demethylases and Tet oxygenases by competing against α-KG binding. However, L2HG is an antagonist, while R2HG (D2HG) is an agonist of α-KG-dependent prolylhydroxylase (EglN).
American journal of ophthalmology, 103(2), 167-179 (1987-02-15)
We studied 49 eyes obtained post mortem from 43 patients who had previously had retinal detachment surgery to evaluate some of the factors known to complicate retinal detachment. The retina had been successfully reattached in 44 of 49 eyes. We
Journal of molecular biology, 429(19), 2895-2906 (2017-08-23)
Methylation of lysine-4 of histone H3 (H3K4men) is an important regulatory factor in eukaryotic transcription. Removal of the transcriptionally activating H3K4 methylation is catalyzed by histone demethylases, including the Jumonji C (JmjC) KDM5 subfamily. The JmjC KDMs are Fe(II) and
Recent findings indicate that mitochondrial respiration regulates blood endothelial cell proliferation; however, its role in differentiating lymphatic endothelial cells (LECs) is unknown. We hypothesized that mitochondria could work as a sensor of LECs' metabolic specific needs by determining their functional
We discovered recently that the central metabolite α-ketoglutarate (α-KG) extends the lifespan of C. elegans through inhibition of ATP synthase and TOR signaling. Here we find, unexpectedly, that (R)-2-hydroxyglutarate ((R)-2HG), an oncometabolite that interferes with various α-KG-mediated processes, similarly extends
Despite its central importance in cellular metabolism, many details remain to be determined regarding subcellular lactate metabolism and its regulation in physiology and disease, as there is sensitive spatiotemporal resolution of lactate distribution, and dynamics remains a technical challenge. Here
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