MGSSHHHHHH SSGLVPRGSH MVDSVYRTRS LGVAAEGLPD QYADGEAARV WQLYIGDTRS RTAEYKAWLL GLLRQHGCQR VLDVACGTGV DSIMLVEEGF SVTSVDASDK MLKYALKERW NRRHEPAFDK WVIEEANWMT LDKDVPQSAE GGFDAVICLG NSFAHLPDCK GDQSEHRLAL KNIASMVRAG GLLVIDHRNY DHILSTGCAP PGKNIYYKSD LTKDVTTSVL IVNNKAHMVT LDYTVQVPGA GQDGSPGLSK FRLSYYPHCL ASFTELLQAA FGGKCQHSVL GDFKPYKPGQ TYIPCYFIHV LKRTD.
GNMT is a tetrameric cytosolic protein that catalyzes the transfer of a methyl group from S-adenosylmethionine (AdoMet) to glycine, producing S-adenosylhomocysteine (AdoHcy) and sarcosine . This reaction is essential for maintaining normal levels of AdoMet, which is a critical methyl donor in various biological processes .
The enzyme’s structure allows it to bind to both AdoMet and glycine, facilitating the methylation process. The human recombinant form of GNMT is produced using E. coli expression systems, which ensures high purity and activity .
GNMT plays a significant role in the regulation of methyl group metabolism. By converting glycine to sarcosine, it helps maintain the balance of AdoMet and AdoHcy, which is vital for numerous methylation reactions in the body . These reactions are involved in DNA methylation, protein methylation, and the synthesis of various biomolecules.
In the liver, GNMT is particularly abundant, constituting up to 3% of the soluble protein in liver cytosol . Its activity is also observed in other tissues, including the pancreas, kidneys, and certain regions of the brain .
Mutations in the GNMT gene can lead to various metabolic disorders. For instance, deficiencies in GNMT activity have been linked to hypermethioninemia, a condition characterized by elevated levels of methionine in the blood . Additionally, GNMT has been implicated in liver diseases, including hepatocellular carcinoma, where its expression is often altered .