Aminooxyacetic Acid, an inhibitor of GABA-t, is also inhibited CBS and CSE with an IC50s of 8.5 and 1.1 μM.
The CCK-8 assay indicated that Aminooxyacetic Acid inhibited the viability of colon cancer cells in a concentration-dependent manner. Aminooxyacetic Acid (100 and 200 mol/L) had no effect on the survival of HCT116 and HT29 cells, respectively [1]. Aminooxyacetic Acid also decreased the glycolytic rate and the levels of extracellular lactate and pyruvate, without affecting the mitochondrial membrane potential of C6 cells[2]. Aminooxyacetic acid inhibits the malate-aspartate shuttle in isolated nerve terminals and prevents the mitochondria from utilizing glycolytic substrates[3].
Aminooxyacetic acid can improve learning and memory in a chronic alcoholism rat model, which may be associated with reduction of hippocampal H2S level and mitochondrial ATPase activity, and up-regulation of myelin basic protein levels in the hippocampus [4]. TCE decreased fetal weight, and this was prevented by Aminooxyacetic Acid but not NAC pre/co-treatment to TCE. Although Aminooxyacetic Acid inhibited CCBL activity in maternal kidney, it did not inhibit CCBL activity in maternal liver and placenta, suggesting that Aminooxyacetic Acid prevention of TCE-induced decreased fetal weight was due to CCBL activity inhibition in the kidneys but not liver or placenta [5]. Tumor (HCT116 cells) growth was significantly reduced by 9 mg/kg/day Aminooxyacetic Acid [6]. Aminooxyacetic acid induced accumulation of GABA in the rat brain [7]. Both H2S biosynthesis inhibition (using Aminooxyacetic Acid) and H2S donation (using AP39) suppresses inflammatory mediator production and reduces multi-organ injury in a murine model of burn injury, both at an early time point and at a later time point [8]. Aminooxyacetic Acid inhibited growth of SUM159, SUM149, and MCF-7 xenografts and c-myc-overexpressing transgenic mouse mammary tumors [9].
References:
[1]. Yue T, Zuo S, et,al. Aminooxyacetic acid (AOAA) sensitizes colon cancer cells to oxaliplatin via exaggerating apoptosis induced by ROS. J Cancer. 2020 Jan 20;11(7):1828-1838. doi: 10.7150/jca.35375. PMID: 32194794; PMCID: PMC7052847.
[2]. Wang C, Chen H, et,al. Malate-aspartate shuttle inhibitor aminooxyacetic acid leads to decreased intracellular ATP levels and altered cell cycle of C6 glioma cells by inhibiting glycolysis. Cancer Lett. 2016 Aug 1;378(1):1-7. doi: 10.1016/j.canlet.2016.05.001. Epub 2016 May 6. PMID: 27157912.
[3]. Kauppinen RA, Sihra TS, et,al. Aminooxyacetic acid inhibits the malate-aspartate shuttle in isolated nerve terminals and prevents the mitochondria from utilizing glycolytic substrates. Biochim Biophys Acta. 1987 Sep 14;930(2):173-8. doi: 10.1016/0167-4889(87)90029-2. PMID: 3620514.
[4]. Du AL, Qin HZ, et,al. Aminooxyacetic acid improves learning and memory in a rat model of chronic alcoholism. Neural Regen Res. 2018 Sep;13(9):1568-1574. doi: 10.4103/1673-5374.237120. PMID: 30127117; PMCID: PMC6126113.
[5]. Su AL, Lash LH, et,al. N-Acetyl-L-cysteine and aminooxyacetic acid differentially modulate trichloroethylene reproductive toxicity via metabolism in Wistar rats. Arch Toxicol. 2021 Apr;95(4):1303-1321. doi: 10.1007/s00204-021-02991-8. Epub 2021 Feb 18. PMID: 33599830; PMCID: PMC8035313.
[6]. Chao C, Zatarain JR,et,al. Cystathionine-beta-synthase inhibition for colon cancer: Enhancement of the efficacy of aminooxyacetic acid via the prodrug approach. Mol Med. 2016 Sep;22:361-379. doi: 10.2119/molmed.2016.00102. Epub 2016 May 16. PMID: 27257787; PMCID: PMC5072412.
[7]. Pagliusi SR, Gomes C, et,al. Aminooxyacetic acid induced accumulation of GABA in the rat brain. Interaction with GABA receptors and distribution in compartments. Naunyn Schmiedebergs Arch Pharmacol. 1983 Apr;322(3):210-5. doi: 10.1007/BF00500767. PMID: 6306485.
[8]. Ahmad A, Szabo C. Both the H2S biosynthesis inhibitor aminooxyacetic acid and the mitochondrially targeted H2S donor AP39 exert protective effects in a mouse model of burn injury. Pharmacol Res. 2016 Nov;113(Pt A):348-355. doi: 10.1016/j.phrs.2016.09.013. Epub 2016 Sep 14. PMID: 27639598.
[9]. Korangath P, Teo WW, et,al.Targeting Glutamine Metabolism in Breast Cancer with Aminooxyacetate. Clin Cancer Res. 2015 Jul 15;21(14):3263-73. doi: 10.1158/1078-0432.CCR-14-1200. Epub 2015 Mar 26. PMID: 25813021; PMCID: PMC4696069.
氨基氧乙酸是 GABA-t 的抑制剂,也可抑制 CBS 和 CSE,IC50 分别为 8.5 和 1.1 μM。
CCK-8 测定表明氨基氧乙酸以浓度依赖性方式抑制结肠癌细胞的活力。氨基氧乙酸(100和200 mol/L)分别对HCT116和HT29细胞的存活没有影响[1]。 Aminoxyacetic Acid 还可以降低糖酵解速率以及细胞外乳酸和丙酮酸的水平,而不影响 C6 细胞的线粒体膜电位[2]。氨氧乙酸抑制孤立神经末梢的苹果酸-天冬氨酸穿梭,并阻止线粒体利用糖酵解底物[3]。
氨基氧乙酸可以改善慢性酒精中毒大鼠模型的学习和记忆,这可能与海马 H2S 水平和线粒体 ATP 酶活性降低以及海马髓鞘碱性蛋白水平上调有关 [4] 。 TCE 降低了胎儿体重,氨氧乙酸可以防止这种情况发生,但 NAC 对 TCE 进行预处理/联合处理则不能。虽然氨基氧乙酸抑制母体肾脏中的 CCBL 活性,但它不抑制母体肝脏和胎盘中的 CCBL 活性,这表明氨基氧乙酸预防 TCE 引起的胎儿体重下降是由于肾脏中的 CCBL 活性抑制,而不是肝脏或胎盘 <sup >[5]。 9 毫克/千克/天的氨基氧乙酸 [6] 显着降低了肿瘤（HCT116 细胞）的生长。氨氧乙酸诱导大鼠脑内 GABA 积累[7]。 H2S 生物合成抑制（使用氨基氧乙酸）和 H2S 捐赠（使用 AP39）均抑制炎症介质的产生并减少小鼠烧伤模型中的多器官损伤,无论是在早期时间点还是在稍后时间点[ 8]。氨基氧乙酸抑制 SUM159、SUM149 和 MCF-7 异种移植物和 c-myc 过表达转基因小鼠乳腺肿瘤的生长[9]。