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

机构式：

特性：紫色或类紫色粉末状

融化度：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]；拉低肿瘤细胞有不确定毒副作用的可溶性氧总体水平^[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]，上下调整抗阻运转在减轻腹型肥胖、增强学习肩部背部肌肉潜能和防冶肩部背部肌肉衰老部分的益处^[6]，调接巨峰葡萄糖粉耐量^[7]，参与者哀老及与哀老对应生理方面變化或疾患发展进步^[8]，参于些癌症晚期及慢性炎症的引发及新况^[9]，参与未成熟T细胞向成熟T细胞的分化^[10]。

分类文章

[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.