Gnmt, or glycine N-methyltransferase, is a key enzyme in one-carbon metabolism. It catalyzes the production of methylglycine (sarcosine) by taking a methyl group from S-adenosyl-L-methionine and methylating glycine, thus clearing methionine from the body [1,2]. This process is crucial for maintaining proper cellular methyl group availability, which is involved in various biological processes such as epigenetic modification [2].

In model organisms, Gnmt has significant impacts. In flies, Gnmt is required for reduced insulin/insulin-like growth factor 1 signaling and dietary restriction to fully extend lifespan [1]. In mice, Gnmt knockout models have shown that Gnmt deficiency has high penetrance in inducing the development of steatohepatitis and hepatocellular carcinoma [2]. Children with Gnmt mutation have elevated liver transaminases, and Gnmt knockout mice develop liver injury, fibrosis, and HCC, indicating that a normal hepatic S-adenosylmethionine (AdoMet) level, which is regulated by Gnmt, is necessary to maintain liver health [3].

In conclusion, Gnmt is essential for regulating methionine metabolism and maintaining proper methyl group availability. Model-based research, especially Gnmt knockout mouse models, has revealed its crucial role in liver-related diseases such as steatohepatitis, liver fibrosis, and hepatocellular carcinoma, highlighting its potential as a therapeutic target and biomarker in these disease areas [2,3].

References:

1. Johnson, Adiv A, Cuellar, Trinna L. 2023. Glycine and aging: Evidence and mechanisms. In Ageing research reviews, 87, 101922. doi:10.1016/j.arr.2023.101922. https://pubmed.ncbi.nlm.nih.gov/37004845/

2. Yen, Chia-Hung, Lin, Yu-Ting, Chen, Heng-Li, Chen, Shih-Yin, Chen, Yi-Ming Arthur. 2012. The multi-functional roles of GNMT in toxicology and cancer. In Toxicology and applied pharmacology, 266, 67-75. doi:10.1016/j.taap.2012.11.003. https://pubmed.ncbi.nlm.nih.gov/23147572/

3. Lu, Shelly C, Mato, José M. . S-adenosylmethionine in liver health, injury, and cancer. In Physiological reviews, 92, 1515-42. doi:10.1152/physrev.00047.2011. https://pubmed.ncbi.nlm.nih.gov/23073625/