GNMT

GNMT (glycine N-methyltransferase) is a highly abundant cytosolic methyltransferase in liver tissue that catalyzes the conversion of glycine to sarcosine using S-adenosylmethionine (SAM) and functions as a major regulator of cellular methyl-group metabolism and the SAM/S-adenosylhomocysteine (SAH) balance^[1]. Mechanistically, GNMT links one-carbon metabolism with epigenetic regulation because alterations in GNMT activity modify intracellular methylation capacity and influence DNA and histone methylation programs^[1][2]. In disease models, GNMT deficiency promotes hepatic steatosis, aberrant methylation, and progressive hepatocellular carcinoma (HCC), supporting its role as a tumor suppressor in liver carcinogenesis^[2][3][4]. GNMT also contributes to hepatic detoxification pathways and regulates the cellular response to environmental carcinogens, including benzo^[a]pyrene and aflatoxin B1, thereby influencing susceptibility to liver injury and tumor development^[1][4]. Compared with related methyltransferases such as NNMT (nicotinamide N-methyltransferase), GNMT primarily controls methionine-cycle homeostasis and methyl-donor flux rather than nicotinamide catabolism, highlighting a distinct metabolic and regulatory function. Beyond its catalytic activity, nuclear-localized GNMT exerts antiproliferative and pro-apoptotic effects that contribute to tumor suppression, indicating that GNMT possesses both metabolic and noncanonical regulatory functions relevant to experimental cancer research^[5].