Glycine N-methyltransferase (GNMT) (GNMT)

Glycine N-methyltransferase (GNMT) is a cytosolic enzyme that plays a pivotal role in regulating methyl group metabolism by catalyzing the conversion of S-adenosylmethionine (SAM) and glycine to S-adenosylhomocysteine (SAH) and sarcosine (UniProt: Q14749). This activity is essential for maintaining the SAM/SAH ratio, which dictates the methylation potential of the cell and prevents the aberrant methylation of DNA and proteins (PubMed: 25613707). The broader class of protein and RNA methyltransferases includes diverse enzymes that modify histones, translation factors, and various RNA species, thereby controlling gene expression and cellular signaling (NCBI: 11062). Clinically, GNMT deficiency or downregulation is a hallmark of hepatocellular carcinoma and other liver pathologies, as it leads to the accumulation of SAM and subsequent epigenetic instability (PubMed: 19144677). Pharmacological intervention in this pathway includes the use of methyltransferase inhibitors like Tazemetostat for oncology indications, as well as metabolic supplements to balance the methionine cycle (FDA: Tazemetostat). However, therapeutic development is complicated by the risk of global epigenetic dysregulation and the need for high specificity to avoid disrupting essential cellular methylation processes (PubMed: 30256124).

Other names

GNMTGlycine methyltransferaseS-adenosyl-L-methionine:glycine methyltransferaseProtein methyltransferaseRNA methyltransferaseGlycine N-methyltransferase and other protein/RNA methyltransferases

Inhibition or modulation of methyltransferase enzymatic activity to regulate the methylation of substrates and maintain S-adenosylmethionine (SAM) homeostasis.