The complex role of glycine N-methyltransferase in metabolism-a review.

Abstract

Background: 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.

Objective: 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.

Results: 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.

Conclusion: 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.