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

结构式：

性状：白色或类白色粉末

溶解度：易溶于水、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]；降低细胞中有潜在毒性的活性氧水平^[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]，调节抗阻运动在减少肥胖、增强肌肉力量和预防肌肉萎缩方面的益处^[6]，调节葡萄糖耐量^[7]，参与衰老及与衰老相关生理变化或疾病发展^[8]，参与某些癌症及炎症的发生及进展^[9]，参与未成熟T细胞向成熟T细胞的分化^[10]。

参考文献

[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.