Disodium (R)-2-Hydroxyglutarate (Synonyms: D-2-HG, D-2-Hydroxyglutaric Acid) |
| カタログ番号GC10981 |
(R)-2-ヒドロキシグルタル酸二ナトリウム ((R)-2-ヒドロキシグルタル酸二ナトリウム) は、神経代謝疾患 D-2-ヒドロキシグルタル酸尿症で蓄積する主要な代謝産物です。
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Cas No.: 103404-90-6
Sample solution is provided at 25 µL, 10mM.
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Information here is from (R)-2-hydroxyglutarate ((R)-2HG) instead of Disodium (R)-2-Hydroxyglutarate. (R)-2HG inhibits adenosine triphosphate (ATP) synthase [1]. The IC50 value has not been found.
ATP synthase containing a rotary motor involved in energy conversion in organisms. It produces ATP from inorganic phosphate and adenosine diphosphate (ADP). It functions using the energy from a respiration- or photosynthesis-generated transmembrane proton-motive force [2].
Data showed that (R)-2HG accumulated in human cancers carrying mutant isocitrate dehydrogenase (IDH) 1 and 2 genes. In IDH1 mutant cells, the inhibition of (R)-2HG to ATP synthase was mirrored. This indicated that (R)-2HG has a growth-suppressive function. In glioblastoma cells, consistently, the inhibition of (R)-2HG to ATP synthase is sufficient for tumor cell killing and growth arrest under glucose limitation conditions, e.g., when ketone bodies are supplied for energy instead of glucose. In cells, treatment with (R)-2HG decreased the rate of ATP synthase-linked oxygen consumption [1].
The normal cellular concentration of (R)-2HG is 200 mM. At this concentration, ATP synthase is unlikely to be significantly inhibited by (R)-2HG. In glioma patients with IDH mutations, (R)-2HG accumulates to 10-100 times of normal levels, and ATP synthase would be possible to be inhibited. (R)-2HG extended the lifespan of C. elegans, in a similar way of α-KG. Data showed that 2-HG increased lifespan ATP-synthase-dependently [1].
References:
[1]. Fu X, Chin RM, Vergnes L, et al. 2-Hydroxyglutarate inhibits ATP synthase and mTOR signaling. Cell metabolism, 2015, 22(3): 508-515.
[2]. Stock D, Leslie AGW and Walker JE. Molecular architecture of the rotary motor in ATP synthase. Science, 1999, 286(5445): 1700-1705.
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