Agxt2-KO Mouse

Agxt2, or alanine-glyoxylate aminotransferase 2, is a multifunctional mitochondrial aminotransferase. It was first identified in 1978. Although initially overlooked due to its lower activity in glyoxylate metabolism compared to AGXT1, it has now been "rediscovered" to have multiple substrates and products. It is involved in key mitochondrial pathways and is potentially important for various physiological functions [1].

Agxt2 has been associated with multiple diseases. Its deficiency in expression or activity may play a role in the progression of cardiovascular or renal diseases through affecting the metabolism of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) [2]. In hepatocellular carcinoma, lower Agxt2 levels are associated with a worse prognosis, and its activation can decrease cholesterol levels in cancer cells, suppressing their growth and metastasis [3]. A SNP (rs37369) in Agxt2 is a risk factor for diabetes mellitus [4]. In cats, genetic variants of Agxt2 are associated with different risks of calcium oxalate stone formation [5]. Also, Agxt2 is identified as a biomarker of acute kidney injury, and its down-regulation may induce AKI [6]. The rs37369 polymorphism of Agxt2 can affect the renal function in chronic heart failure patients, especially in smokers [7]. Missense variants of Agxt2 may be related to vascular diseases like hypertension and diabetes mellitus via the nitric oxide system [8]. Another SNP (rs180749) is associated with depressive symptoms [9]. In Egyptians, genetic variants of Agxt2 are correlated with serum ADMA and SDMA levels and the incidence of coronary artery disease [10].

In conclusion, Agxt2 is a multifunctional mitochondrial aminotransferase involved in various biological processes. Studies, including those on genetic variants, have revealed its significance in multiple disease areas such as cardiovascular, renal, hepatic, metabolic, and neurological diseases. Understanding Agxt2's functions through these genetic-based studies provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Rodionov, Roman N, Jarzebska, Natalia, Weiss, Norbert, Lentz, Steven R. 2014. AGXT2: a promiscuous aminotransferase. In Trends in pharmacological sciences, 35, 575-82. doi:10.1016/j.tips.2014.09.005. https://pubmed.ncbi.nlm.nih.gov/25294000/

2. Hu, Xiao-Lei, Li, Mu-Peng, Song, Pei-Yuan, Tang, Jie, Chen, Xiao-Ping. 2017. AGXT2: An unnegligible aminotransferase in cardiovascular and urinary systems. In Journal of molecular and cellular cardiology, 113, 33-38. doi:10.1016/j.yjmcc.2017.09.010. https://pubmed.ncbi.nlm.nih.gov/28970090/

3. Chen, Tian, Xiang, Lunjian, Zhang, Wenjin, Xia, Zhenyi, Chen, Weixian. 2024. AGXT2 Suppresses the Proliferation and Dissemination of Hepatocellular Carcinoma Cells by Modulating Intracellular Lipid Metabolism. In Journal of hepatocellular carcinoma, 11, 1623-1639. doi:10.2147/JHC.S470250. https://pubmed.ncbi.nlm.nih.gov/39206420/

4. Kumon, Hiroshi, Miyake, Yoshihiro, Yoshino, Yuta, Kawamoto, Ryuichi, Ueno, Shu-Ichi. 2022. Functional AGXT2 SNP rs37369 Variant Is a Risk Factor for Diabetes Mellitus: Baseline Data From the Aidai Cohort Study in Japan. In Canadian journal of diabetes, 46, 829-834. doi:10.1016/j.jcjd.2022.06.004. https://pubmed.ncbi.nlm.nih.gov/35961823/

5. Hall, Jean A, Panickar, Kiran S, Brockman, Jeffrey A, Jewell, Dennis E. 2022. Cats with Genetic Variants of AGXT2 Respond Differently to a Dietary Intervention Known to Reduce the Risk of Calcium Oxalate Stone Formation. In Genes, 13, . doi:10.3390/genes13050791. https://pubmed.ncbi.nlm.nih.gov/35627178/

6. Wei, Jinshuang, Zhang, Junlin, Wei, Junyu, Lei, Fengying, Qin, Yuanhan. 2023. Identification of AGXT2, SHMT1, and ACO2 as important biomarkers of acute kidney injury by WGCNA. In PloS one, 18, e0281439. doi:10.1371/journal.pone.0281439. https://pubmed.ncbi.nlm.nih.gov/36735737/

7. Hu, Xiao-Lei, Zeng, Wen-Jing, Li, Mu-Peng, Zhang, Ke, Chen, Xiao-Ping. 2017. AGXT2 rs37369 polymorphism predicts the renal function in patients with chronic heart failure. In Gene, 637, 145-151. doi:10.1016/j.gene.2017.09.038. https://pubmed.ncbi.nlm.nih.gov/28942034/

8. Yoshino, Yuta, Kumon, Hiroshi, Mori, Takaaki, Iga, Jun-Ichi, Ueno, Shu-Ichi. 2021. Effects of AGXT2 variants on blood pressure and blood sugar among 750 older Japanese subjects recruited by the complete enumeration survey method. In BMC genomics, 22, 287. doi:10.1186/s12864-021-07612-3. https://pubmed.ncbi.nlm.nih.gov/33879046/

9. Kumon, Hiroshi, Miyake, Yoshihiro, Yoshino, Yuta, Kawamoto, Ryuichi, Ueno, Shu-Ichi. 2024. Functional AGXT2 SNP rs180749 variant and depressive symptoms: Baseline data from the Aidai Cohort Study in Japan. In Journal of neural transmission (Vienna, Austria : 1996), 131, 267-274. doi:10.1007/s00702-024-02742-w. https://pubmed.ncbi.nlm.nih.gov/38261033/

10. Amir, Mina, Hassanein, Sally I, Abdel Rahman, Mohamed F, Gad, Mohamed Z. 2018. AGXT2 and DDAH-1 genetic variants are highly correlated with serum ADMA and SDMA levels and with incidence of coronary artery disease in Egyptians. In Molecular biology reports, 45, 2411-2419. doi:10.1007/s11033-018-4407-1. https://pubmed.ncbi.nlm.nih.gov/30284143/