带你了解AKG（α-酮戊二酸）

中文名称：α-酮戊二酸，又称2-氧代戊二酸，2-氧代-1,5-戊二酸

英文名称：α-ketoglutaric acid，2-oxoglutaric acid，2-oxopentanedioic acid，简称AKG

CAS号：328-50-7

分子式：C₅H₆O₅

框架式：

遗传性状：暗红色或类暗红色粉沫

熔化分解度：溶解于水、醇和酮等

pH：1-3

常见的存在形式：α-酮戊二酸、α-酮戊二酸钙、精氨酸-α-酮戊二酸（1:1、2:1）、鸟氨酸-α-酮戊二酸（1:1、2:1）、瓜氨酸-α-酮戊二酸（1:1、2:1）

生理功能及功效：AKG是三羧酸循环的中间产物，三羧酸循环是所有需氧生物中普遍存在的核心代谢途径，其主要功能是将乙酰辅酶A彻底氧化分解，生成二氧化碳和水，同时产生能量丰富的分子，如NADH、FADH2和ATP。此外，AKG在多种代谢反应中也起到重要作用，如参与关键氨基酸的生成，并在此过程中调节细胞内碳、氮和氨的水平^[1]；降低内部含有不确定性渗透性的化学活化氧质量^[2,3]；合成神经递质γ-氨基丁酸^[4]等。在多项临床前研究中，AKG还可直接激活或作为辅助因子激活各种细胞功能，包括调节肾功能^[5]，调节器抗阻有氧运动在减轻高血压、不断增强全身肌肉群能力和预防措施全身肌肉群回缩这方面的益处^[6]，控制红提糖耐量^[7]，参与性苍老及与苍老相应的生理变变或急病经济发展^[8]，加入某一肠癌及感染的突发及重大进展^[9]，参与未成熟T细胞向成熟T细胞的分化^[10]。

选取论文

[1] Wu N, Yang M, Gaur U, Xu H, Yao Y, Li D (2016). Alpha-Ketoglutarate: Physiological Functions and Applications. Biomolecules & Therapeutics. 24 (1): 1–8.

[2] Liu S, He L, Yao K (2018). The Antioxidative Function of Alpha-Ketoglutarate and Its Applications. BioMed Research International. 2018: 3408467.

[3] Kroupina K, Bémeur C, Rose CF (2022). Amino acids, ammonia, and hepatic encephalopathy. Analytical Biochemistry. 649: 114696.

[4] Kaneko T, Mizuno N (1994). Glutamate-synthesizing enzymes in GABAergic neurons of the neocortex: a double immunofluorescence study in the rat. Neuroscience. 61 (4): 839–49.

[5] Tokonami N, Morla L, Centeno G, Mordasini D, Ramakrishnan SK, Nikolaeva S, Wagner CA, Bonny O, Houillier P, Doucet A, Firsov D (2013). α-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism. The Journal of Clinical Investigation. 123 (7): 3166–71.

[6] Yuan Y, Xu P, Jiang Q, Cai X, Wang T, Peng W, Sun J, Zhu C, Zhang C, Yue D, He Z, Yang J, Zeng Y, Du M, Zhang F, Ibrahimi L, Schaul S, Jiang Y, Wang J, Sun J, Wang Q, Liu L, Wang S, Wang L, Zhu X, Gao P, Xi Q, Yin C, Li F, Xu G, Zhang Y, Shu G (2020). Exercise-induced α-ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1-dependent adrenal activation. The EMBO Journal. 39 (7): e103304.

[7] Yuan Y, Zhu C, Wang Y, Sun J, Feng J, Ma Z, Li P, Peng W, Yin C, Xu G, Xu P, Jiang Y, Jiang Q, Shu G (2022). α-Ketoglutaric acid ameliorates hyperglycemia in diabetes by inhibiting hepatic gluconeogenesis via serpina1e signaling. Science Advances. 8 (18): eabn2879.

[8] Asadi Shahmirzadi A, Edgar D, Liao CY, Hsu YM, Lucanic M, Asadi Shahmirzadi A, Wiley CD, Gan G, Kim DE, Kasler HG, Kuehnemann C, Kaplowitz B, Bhaumik D, Riley RR, Kennedy BK, Lithgow GJ (2020). Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice. Cell Metabolism. 32 (3): 447–456.e6.

[9] Manni W, Jianxin X, Weiqi H, Siyuan C, Huashan S (2022). JMJD family proteins in cancer and inflammation. Signal Transduction and Targeted Therapy. 7 (1): 304.

[10] Klysz D, Tai X, Robert PA, Craveiro M, Cretenet G, Oburoglu L, Mongellaz C, Floess S, Fritz V, Matias MI, Yong C, Surh N, Marie JC, Huehn J, Zimmermann V, Kinet S, Dardalhon V, Taylor N (2015). Glutamine-dependent α-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation. Science Signaling. 8 (396): ra97.