Suzauddula Md, Islam Md Numan, Ahmed Tanvir
Department of Nutrition and Food Engineering, Daffodil International University, Dhaka, Bangladesh.
Department of Nutrition and Food Technology, Jashore University of Science and Technology, Jashore, 7408, Bangladesh.
Mol Biol Rep. 2025 Mar 1;52(1):271. doi: 10.1007/s11033-025-10374-w.
Glycine N-methyltransferase (GNMT) is an enzyme predominantly found in the liver, playing a crucial role in various metabolic pathways. GNMT is involved in transmethylation, transsulfuration, one-carbon metabolism, energy metabolism, and DNA methylation. Deletion or Knockdown of GNMT influences the expression of several key metabolic enzymes by accumulating S-adenosylmethionine (SAM). Dysregulation of GNMT and these metabolic enzymes can lead to metabolic dysfunction and chronic diseases.
To provide a comprehensive review of the impact of Glycine N-methyltransferase (GNMT) on metabolism, focusing on its epigenetic and genetic mechanisms, its role in metabolic pathways, and its association with chronic diseases.
GNMT is highly expressed in the liver and exerts direct and indirect effects on various metabolic pathways, including transmethylation, transsulfuration, one-carbon metabolism, energy metabolism, and global DNA methylation. Current understanding suggests that GNMT operates through both epigenetic and genetic mechanisms, influencing the expression of key metabolic enzymes such as BHMT, NNMT, PEMT, DNMTs, CBS, and MTHFR through the accumulation of S-adenosylmethionine. Dysregulation of these proteins not only affects metabolic function but also contributes to the development of several chronic diseases. Furthermore, the level of GNMT protein has been directly linked to non-alcoholic fatty liver disease, with its function being gender, age, and organ specific. At the same time, GNMT and disease progression correlate, dietary supplementation and pharmacological approaches have shown promise in controlling GNMT levels.
GNMT plays a multifaceted role in metabolism, influencing various pathways and contributing to chronic disease development. Understanding its mechanisms and interactions opens avenues for targeted dietary and pharmacological therapies to manage GNMT-related metabolic dysfunction.
甘氨酸N-甲基转移酶（GNMT）是一种主要存在于肝脏中的酶，在各种代谢途径中起关键作用。GNMT参与转甲基作用、转硫作用、一碳代谢、能量代谢和DNA甲基化。GNMT的缺失或敲低通过积累S-腺苷甲硫氨酸（SAM）影响几种关键代谢酶的表达。GNMT和这些代谢酶的失调可导致代谢功能障碍和慢性疾病。
全面综述甘氨酸N-甲基转移酶（GNMT）对代谢的影响，重点关注其表观遗传和遗传机制、在代谢途径中的作用以及与慢性疾病的关联。
GNMT在肝脏中高度表达，对各种代谢途径产生直接和间接影响，包括转甲基作用、转硫作用、一碳代谢、能量代谢和全基因组DNA甲基化。目前的认识表明，GNMT通过表观遗传和遗传机制发挥作用，通过S-腺苷甲硫氨酸的积累影响关键代谢酶如BHMT、NNMT、PEMT、DNMTs、CBS和MTHFR的表达。这些蛋白质的失调不仅影响代谢功能，还促成几种慢性疾病的发展。此外，GNMT蛋白水平与非酒精性脂肪性肝病直接相关，其功能具有性别、年龄和器官特异性。同时，GNMT与疾病进展相关，膳食补充和药理学方法在控制GNMT水平方面显示出前景。
GNMT在代谢中发挥多方面作用，影响各种途径并促成慢性疾病发展。了解其机制和相互作用为管理与GNMT相关的代谢功能障碍的靶向饮食和药物治疗开辟了途径。
