Nε-(1-Carboxyethyl)-L-lysine

Nε-(1-Carboxyethyl)-L-lysine is an advanced glycation end product (AGE) formed by the reaction of methylglyoxal with lysine residues in proteins^[1-2]. Nε-(1-Carboxyethyl)-L-lysine can bind to the receptor for advanced glycation end products (RAGE) to influence cell signaling, modulating processes such as inflammatory responses, cell proliferation, and apoptosis. Nε-(1-Carboxyethyl)-L-lysine is applicable in research on aging, metabolism, and diabetes, as well as in the evaluation of Maillard reactions in food science^[3-4].

In vitro, endothelial progenitor cells were treated with Nε-(1-Carboxyethyl)-L-lysine at concentrations ranging from 46ng/mL to 300μg/mL for 24-72 hours. Nε-(1-Carboxyethyl)-L-lysine downregulated the phosphorylation level of the MAPK signaling pathway and significantly inhibited the proliferation of endothelial progenitor cells, but Nε-(1-Carboxyethyl)-L-lysine had no significant effect on cell migration, tube formation ability, or apoptosis levels^[5]. LO2 cells were treated with Nε-(1-Carboxyethyl)-L-lysine (10–50μM) for 24 hours. Nε-(1-Carboxyethyl)-L-lysine significantly upregulated the expression of RAGE and TET1 and promoted hypomethylation of the RAGE promoter^[6].

In vivo, high-fat diet (HFD)-induced obese C57BL/6 mice were orally administered Nε-(1-Carboxyethyl)-L-lysine (7.5mg/kg/day) for 12 weeks. Nε-(1-Carboxyethyl)-L-lysine significantly reduced the mice body weight and simultaneously increased the accumulation level of Nε-(1-Carboxyethyl)-L-lysine in the liver^[7].

References:
[1] Nemet I, Varga-Defterdarović L, Turk Z. Methylglyoxal in food and living organisms. Mol Nutr Food Res. 2006 Dec;50(12):1105-17.
[2] Oliveira AL, de Oliveira MG, Mónica FZ, et al. Methylglyoxal and Advanced Glycation End Products (AGEs): Targets for the Prevention and Treatment of Diabetes-Associated Bladder Dysfunction? Biomedicines. 2024 Apr 23;12(5):939.
[3] Hansen F, Battú CE, Dutra MF, et al. Methylglyoxal and carboxyethyllysine reduce glutamate uptake and S100B secretion in the hippocampus independently of RAGE activation. Amino Acids. 2016 Feb;48(2):375-85.
[4] Serrano JCE, Baena-Fustegueras JA, Martin-Gari M, et al. Adipose Tissue Protein Glycoxidation is Associated with Weight-Loss Potential. Obesity (Silver Spring). 2019 Jul;27(7):1133-1140.
[5] Zhu J, Yang K, Jing Y, et al. The effects of low-dose nepsilon-(carboxymethyl)lysine (CML) and nepsilon-(carboxyethyl)lysine (CEL), two main glycation free adducts considered as potential uremic toxins, on endothelial progenitor cell function. Cardiovasc Diabetol. 2012 Aug 1;11:90.
[6] Wu X, Shi X, Chen X, et al. Advanced glycation end products regulate the receptor of AGEs epigenetically. Front Cell Dev Biol. 2023 Feb 14;11:1062229.
[7] Huang SF, Chang YT, Hsia SM, et al. Distinct effects of methylglyoxal-derived hydroimidazolone 1, Nε-carboxyethyllysine, and an advanced glycation end product-rich diet on lipid metabolism, gut microbiota, and secondary bile acids in high-fat diet-induced obese mice. Food Chem. 2025 Nov 15;492(Pt 3):145634.

Nε-(1-Carboxyethyl)-L-lysine是一种晚期糖基化终末产物（AGE），由甲基乙二醛与蛋白质中的赖氨酸残基反应生成^[1-2]。Nε-(1-Carboxyethyl)-L-lysine可与晚期糖基化终末产物受体（RAGE）结合影响细胞信号传导，调节炎症反应、细胞增殖和凋亡等过程。Nε-(1-Carboxyethyl)-L-lysine可用于衰老、代谢和糖尿病研究以及食品科学中美拉德反应的评估^[3-4]。

在体外，Nε-(1-Carboxyethyl)-L-lysine（46ng/mL至300μg/mL）处理内皮祖细胞24-72小时。Nε-(1-Carboxyethyl)-L-lysine可下调MAPK信号通路的磷酸化水平，显著抑制内皮祖细胞的增殖，但对细胞的迁移、成管形成能力和凋亡水平没有显著影响^[5]。Nε-(1-Carboxyethyl)-L-lysine（10–50μM）处理LO2细胞24小时，显著上调RAGE和TET1表达，同时促进RAGE启动子低甲基化^[6]。

在体内，Nε-(1-Carboxyethyl)-L-lysine（7.5mg/kg/day）口服给药处理高脂饮食（HFD）诱导的肥胖C57BL/6小鼠12周。Nε-(1-Carboxyethyl)-L-lysine显著降低了小鼠的体重，同时增加了肝脏中Nε-(1-Carboxyethyl)-L-lysine的蓄积水平^[7]。