2-Ketoglutaric acid is a reversible inhibitor of tyrosinase, with an IC50 value of 15 ± 0.5mM[1]. 2-Ketoglutaric acid is naturally found in organisms and is an intermediate in the production of ATP or GTP in the Krebs cycle[2]. Widely used as an antioxidant, 2-Ketoglutaric acid reduced cyanide-induced GSH depletion and DNA damage in rat in vitro and in vivo models[3].
In vitro, 2-Ketoglutaric acid treatment at 0.1mM for 8 days promoted cell growth in C2C12 cells and decreased intracellular glucose consumption and ammonia production[4]. Pretreatment of rabbit dermal papilla cells with 6mM 2-Ketoglutaric acid for 24h alleviated the H2O2-induced decrease in cell viability, reduced ROS accumulation, and restored mitochondrial membrane potential damaged by oxidative stress[5]. Pretreatment with 5mM 2-Ketoglutaric acid for 30min significantly prevented 5mM potassium cyanide-induced cell toxicity and attenuated mitochondrial dysfunction in rat thymocytes[6].
In vivo, 2-Ketoglutaric acid treatment via oral administration at a dose of 10mg/kg/day for 14 days significantly inhibited dextran sulfate sodium-induced intestinal injury, and prevented disruption of gut microbial homeostasis in a mouse model of colitis[7]. Oral administration of 2-Ketoglutaric acid at a dose of 10mg/kg daily for 10 days helped to repair the intestinal barrier damage induced by high altitude exposure in mice[8].
References:
[1] Gou L, Lee J, Yang J M, et al. The effect of alpha-ketoglutaric acid on tyrosinase activity and conformation: Kinetics and molecular dynamics simulation study[J]. International Journal of Biological Macromolecules, 2017, 105: 1654-1662.
[2] Huergo L F, Dixon R. The emergence of 2-oxoglutarate as a master regulator metabolite[J]. Microbiology and Molecular Biology Reviews, 2015, 79(4): 419-435.
[3] Liu S, He L, Yao K. The antioxidative function of alpha‐ketoglutarate and its applications[J]. BioMed research international, 2018, 2018(1): 3408467.
[4] Yang B, Liu Y, Steinacker J M. α-Ketoglutarate stimulates cell growth through the improvement of glucose and glutamine metabolism in C2C12 cell culture[J]. Frontiers in Nutrition, 2023, 10: 1145236.
[5] Wang X, Li S, Chen J, et al. Exogenous Alpha-Ketoglutaric Acid Alleviates the Rabbit Dermal Papilla Cell Oxidative Damage Caused by Hydrogen Peroxide Through the ERK/Nrf2 Signaling Pathway[J]. Antioxidants, 2025, 14(4): 455.
[6] Bhattacharya R, Rao P V L, Vijayaraghavan R. In vitro and in vivo attenuation of experimental cyanide poisoning by α-ketoglutarate[J]. Toxicology Letters, 2002, 128(1-3): 185-195.
[7] Kim S, Jang S H, Kim M J, et al. Hybrid nutraceutical of 2-ketoglutaric acid in improving inflammatory bowel disease: Role of prebiotics and TAK1 inhibitor[J]. Biomedicine & Pharmacotherapy, 2024, 171: 116126.
[8] Sun X, Li W, Chen G, et al. Faecalibacterium duncaniae Mitigates Intestinal Barrier Damage in Mice Induced by High-Altitude Exposure by Increasing Levels of 2-Ketoglutaric Acid[J]. Nutrients, 2025, 17(8): 1380.
2-Ketoglutaric acid是一种可逆的酪氨酸酶抑制剂，IC50值为15 ± 0.5mM[1]。2-Ketoglutaric acid天然存在于生物体内，是三羧酸循环中ATP或GTP生成的关键中间体[2]。作为抗氧化剂，2-Ketoglutaric acid在大鼠体外和体内模型中能减少氰化物诱导的谷胱甘肽（GSH）耗竭和DNA损伤[3]。
在体外，0.1mM的2-Ketoglutaric acid处理C2C12细胞8天可促进细胞生长，降低细胞内葡萄糖消耗和氨产量[4]。6mM的2-Ketoglutaric acid预处理兔真皮乳头细胞24小时能缓解H2O2诱导的细胞活力下降，减少ROS积累并恢复氧化应激损伤的线粒体膜电位[5]。5mM的2-Ketoglutaric acid预处理30分钟可显著防止5mM氰化钾诱导的大鼠胸腺细胞毒性，并减轻线粒体功能障碍[6]。
在体内，2-Ketoglutaric acid以10mg/kg/day的剂量口服给药14天，可显著抑制葡聚糖硫酸钠诱导的肠道损伤，并防止结肠炎小鼠肠道微生物稳态的破坏[7]。每日口服10mg/kg剂量的2-Ketoglutaric acid（持续10天）有助于修复高海拔暴露引起的小鼠肠道屏障损伤[8]。