在U-87MG細(xì)胞中,(R)-2-Hydroxyglutarate作為α-KG的弱拮抗劑抑制α-KG依賴性組蛋白脫甲基化酶,并增加H3K9和H3K79的二甲基化作用。此外,(R)-2-Hydroxyglutarate抑制ATP合酶與mTOR信號,因此引起生長阻滯和腫瘤細(xì)胞殺傷。
D-α-Hydroxyglutaric acid strongly inhibits glucose utilization, CO 2 production and the respiratory chain in rat cerebral cortex and human skeletal muscle, as well as in submitochondrial particles from bovine heart, suggesting an impairment of the aerobic metabolism. D-α-Hydroxyglutaric acid has also been proposed as an endogenous excitotoxic organic acid because it significantly decreased cell viability in neuronal cultures from chick embryo telencephalons and from neonatal rat hippocampus through stimulation of specific NMDA glutamate receptors. D-α-Hydroxyglutaric acid (0.01-1 mM) significantly increases chemiluminescence and thiobarbituric acid-reactive substances (TBA-RS) and decreased total antioxidant reactivity (TAR) values in the cortical supernatants in 30-day-old-rats.