2-Ketoglutaric acid
(Synonyms: α-酮戊二酸; Alpha-Ketoglutaric acid) 目录号 : GC30136An intermediate in the citric acid cycle
Cas No.:328-50-7
Sample solution is provided at 25 µL, 10mM.
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- Purity: >98.00%
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α-Ketoglutaric acid is an α-keto acid and a rate-determining metabolic intermediate in the citric acid cycle in its conjugate base form, α-ketoglutarate.1,2 It is formed via oxidative decarboxylation of isocitrate by isocitrate dehydrogenase (IDH), oxidative deamination of glutamate by glutamate dehydrogenase, or by pyridoxal phosphate-dependent transamination.2 α-Ketoglutaric acid is decarboxylated to succinyl-CoA by α-ketoglutarate dehydrogenase, a rate limiting step in the citric acid cycle. It is a precursor of glutamine and glutamate, energy sources for enterocytes and various immune cells, and an antioxidant with roles in immune homeostasis, aging, protein synthesis, and bone development.2,3
1.Krebs, H.A., Salvin, E., and Johnson, W.A.The formation of citric and α-ketoglutaric acids in the mammalian bodyBiochem. J.32(1)113-117(1938) 2.Wu, N., Yang, M., Gaur, U., et al.Alpha-ketoglutarate: Physiological functions and applicationsBiomol. Ther. (Seoul)24(1)1-8(2016) 3.Liu, S., He, L., and Yao, K.The antioxidative function of alpha-ketoglutarate and its applicationsBiomed. Res. Int.3408467(2018)
Cas No. | 328-50-7 | SDF | |
别名 | α-酮戊二酸; Alpha-Ketoglutaric acid | ||
Canonical SMILES | OC(=O)CCC(=O)C(O)=O | ||
分子式 | C5H6O5 | 分子量 | 146.1 |
溶解度 | Water : 50 mg/mL (342.23 mM) | 储存条件 | Store at -20°C |
General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。 为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。 |
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Shipping Condition | 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。 |
制备储备液 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 6.8446 mL | 34.2231 mL | 68.4463 mL |
5 mM | 1.3689 mL | 6.8446 mL | 13.6893 mL |
10 mM | 0.6845 mL | 3.4223 mL | 6.8446 mL |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
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% DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度: mg/ml;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL,
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL saline,混匀澄清。
1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
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α-Ketoglutaric acid ameliorates hyperglycemia in diabetes by inhibiting hepatic gluconeogenesis via serpina1e signaling
Previously, we found that α-ketoglutaric acid (AKG) stimulates muscle hypertrophy and fat loss through 2-oxoglutarate receptor 1 (OXGR1). Here, we demonstrated the beneficial effects of AKG on glucose homeostasis in a diet-induced obesity (DIO) mouse model, which are independent of OXGR1. We also showed that AKG effectively decreased blood glucose and hepatic gluconeogenesis in DIO mice. By using transcriptomic and liver-specific serpina1e deletion mouse model, we further demonstrated that liver serpina1e is required for the inhibitory effects of AKG on hepatic gluconeogenesis. Mechanistically, we supported that extracellular AKG binds with a purinergic receptor, P2RX4, to initiate the solute carrier family 25 member 11 (SLC25A11)-dependent nucleus translocation of intracellular AKG and subsequently induces demethylation of lysine 27 on histone 3 (H3K27) in the seprina1e promoter region to decrease hepatic gluconeogenesis. Collectively, these findings reveal an unexpected mechanism for control of hepatic gluconeogenesis using circulating AKG as a signal molecule.
Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice
Metabolism and aging are tightly connected. Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid (TCA) cycle, and its levels change upon fasting, exercise, and aging. Here, we investigate the effect of alpha-ketoglutarate (delivered in the form of a calcium salt, CaAKG) on healthspan and lifespan in C57BL/6 mice. To probe the relationship between healthspan and lifespan extension in mammals, we performed a series of longitudinal, clinically relevant measurements. We find that CaAKG promotes a longer, healthier life associated with a decrease in levels of systemic inflammatory cytokines. We propose that induction of IL-10 by dietary AKG suppresses chronic inflammation, leading to health benefits. By simultaneously reducing frailty and enhancing longevity, AKG, at least in the murine model, results in a compression of morbidity.
Alpha-Ketoglutarate dietary supplementation to improve health in humans
Alpha-ketoglutarate (AKG) is an intermediate in the Krebs cycle involved in various metabolic and cellular pathways. As an antioxidant, AKG interferes in nitrogen and ammonia balance, and affects epigenetic and immune regulation. These pleiotropic functions of AKG suggest it may also extend human healthspan. Recent studies in worms and mice support this concept. A few studies published in the 1980s and 1990s in humans suggested the potential benefits of AKG in muscle growth, wound healing, and in promoting faster recovery after surgery. So far there are no recently published studies demonstrating the role of AKG in treating aging and age-related diseases; hence, further clinical studies are required to better understand the role of AKG in humans. This review will discuss the regulatory role of AKG in aging, as well as its potential therapeutic use in humans to treat age-related diseases.
α-Ketoglutarate inhibits autophagy
The metabolite α-ketoglutarate is membrane-impermeable, meaning that it is usually added to cells in the form of esters such as dimethyl -ketoglutarate (DMKG), trifluoromethylbenzyl α-ketoglutarate (TFMKG) and octyl α-ketoglutarate (O-KG). Once these compounds cross the plasma membrane, they are hydrolyzed by esterases to generate α-ketoglutarate, which remains trapped within cells. Here, we systematically compared DMKG, TFMKG and O-KG for their metabolic and functional effects. All three compounds similarly increased the intracellular levels of α-ketoglutarate, yet each of them had multiple effects on other metabolites that were not shared among the three agents, as determined by mass spectrometric metabolomics. While all three compounds reduced autophagy induced by culture in nutrient-free conditions, TFMKG and O-KG (but not DMKG) caused an increase in baseline autophagy in cells cultured in complete medium. O-KG (but neither DMKG nor TFMK) inhibited oxidative phosphorylation and exhibited cellular toxicity. Altogether, these results support the idea that intracellular α-ketoglutarate inhibits starvation-induced autophagy and that it has no direct respiration-inhibitory effect.
Cytokine-like Roles for Metabolites in Immunity
Metabolites have functions in the immune system independent of their conventional roles as sources or intermediates in biosynthesis and bioenergetics. We are still in the pioneering phase of gathering information about the functions of specific metabolites in immunoregulation. In this review, we cover succinate, itaconate, α-ketoglutarate, and lactate as examples. Each of these metabolites has a different story of how their immunoregulatory functions were discovered and how their roles in the complex process of inflammation were revealed. Parallels and interactions are emerging between metabolites and cytokines, well-known immunoregulators. We depict molecular mechanisms by which metabolites prime cellular and often physiological changes focusing on intra- and extra-cellular activities and signaling pathways. Possible therapeutic opportunities for immune and inflammatory diseases are emerging.