| Identification | Back Directory | [Name]
Octyl-α-ketoglutarate | [CAS]
876150-14-0 | [Synonyms]
Octyl-α-KG
Octyl-α-ketoglutarate
QNFIHKFBQFJVKV-UHFFFAOYSA-N
Octyl-.alpha.-ketoglutarate
Pentanedioic acid, 2-oxo-, 1-octyl ester | [Molecular Formula]
C13H22O5 | [MDL Number]
MFCD31697747 | [MOL File]
876150-14-0.mol | [Molecular Weight]
258.31 |
| Chemical Properties | Back Directory | [storage temp. ]
-20°C | [solubility ]
Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly) | [form ]
oil | [color ]
colorless to yellow | [Stability:]
Hygroscopic |
| Hazard Information | Back Directory | [Uses]
Octyl-α-ketoglutarate is a prolyl hydroxylases substrate which accumulates rapidly in cells with dysfunctional tricarboxylic acid cycle. Octyl-α-ketoglutarate also prevents succinate or fumarate mediated inhibition of prolyl hydroxylases. | [Biological Activity]
octyl-α-ketoglutarate is a stable, cell-permeable form of α-ketoglutarate, a substrate of prolyl hydroxylases (phd) [1][2].the high turnover of hifα is initiated by prolyl hydroxylases (phd), which hydroxylate proline residues on the oxygen-dependent degradation (odd) domain of hifα, facilitating ubiquitination and degradation. to catalyze proline hydroxylation, phds convert molecular oxygen and α-ketoglutarate to carbon dioxide and succinate [2]. loss of idh1 activity would reduce cellular levels of α-kg [3].octyl-α-ketoglutarate is a cell-permeating α-ketoglutarate derivative, which built up rapidly and preferentially in cells with a dysfunctional tca cycle. octyl-α-ketoglutarate increased intracellular levels of freeα-ketoglutaric acid by approximately fourfold. in hek293-derived cell lines expressing both a gfp-odd fusion protein and ha-tagged pvhl, octyl-α-ketoglutarate reactivated phd activity inhibited by succinate or fumarate. octyl-α-ketoglutarate restored hydroxylation and targeted hif1 for ubiquitylation and proteasomally mediated degradation [2]. octyl-α-ketoglutarate inhibited the hif-1α induction caused by idh1 knockdown in hela cells or overexpression of idh1r132h mutant in u-87mg cells, suggesting a reduction in idh1 activity caused a reduction in α-kg levels that in turn led to stabilization of hif-1α [3]. | [storage]
Store at -20°C | [References]
[1]. gottlieb e, tomlinson ip. mitochondrial tumour suppressors: a genetic and biochemical update. nat rev cancer. 2005 nov;5(11):857-66.
[2]. mackenzie ed, selak ma, tennant da, et al. cell-permeating alpha-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells. mol cell biol. 2007 may;27(9):3282-9.
[3]. zhao s, lin y, xu w, et al. glioma-derived mutations in idh1 dominantly inhibit idh1 catalytic activity and induce hif-1alpha. science. 2009 apr 10;324(5924):261-5. |
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