Enzymes

GNMT (Glycine N-Methyltransferase)

Enzyme that methylates glycine to sarcosine using SAMe; major regulator of SAMe levels; folate-inhibited.

EnzymesBrowse enzymes
GNMT (Glycine N-Methyltransferase) pathway diagram

Glycine N-Methyltransferase (GNMT) is a highly abundant enzyme, especially in liver, that transfers a methyl group from SAMe to glycine, producing sarcosine and SAH. GNMT serves as a metabolic buffer to regulate SAMe and methyl group availability. When SAMe levels are high, GNMT activity increases to convert excess SAMe to SAH.

GNMT is inhibited by 5-methylTHF, connecting folate status to methylation regulation. Low folate = less inhibition = more GNMT activity = lower SAMe. This explains why folate deficiency can impair methylation even when methionine intake is adequate. GNMT variants have been associated with various cancers and liver disease.

GNMT deficiency causes persistent hypermethioninemia.

Metabolic Connections

GNMT (Glycine N-Methyltransferase) connects to 8 other pathways.

Cofactors

5-MTHF (5-Methyltetrahydrofolate)

5-MTHF (5-Methyltetrahydrofolate)

5-MTHF inhibits GNMT, preserving SAMe when folate is adequate

Primary circulating folate; methyl donor for homocysteine remethylation via MTR; product of MTHFR.

Amino Acids

Glycine

Glycine

GNMT methylates glycine to sarcosine

Simplest amino acid with diverse roles - glutathione component, collagen synthesis, neurotransmission, and methylation.

Glycine

Glycine

GNMT methylates glycine to sarcosine using SAMe as methyl donor

Simplest amino acid with diverse roles - glutathione component, collagen synthesis, neurotransmission, and methylation.

Sarcosine (N-Methylglycine)

Sarcosine (N-Methylglycine)

Sarcosine is the product of GNMT

Intermediate between DMG and glycine; donates methyl group to folate; elevated in prostate cancer.

Sarcosine (N-Methylglycine)

Sarcosine (N-Methylglycine)

GNMT can form sarcosine from glycine using SAMe

Intermediate between DMG and glycine; donates methyl group to folate; elevated in prostate cancer.

Metabolites

S-Adenosylhomocysteine (SAH)

S-Adenosylhomocysteine (SAH)

SAH is produced when GNMT uses SAMe

Product of SAMe after methyl group donation; must be rapidly converted to homocysteine to prevent methylation inhibition.

Methylation

SAMe

SAMe

SAMe is consumed by GNMT as methyl donor; GNMT regulates SAMe levels

S-Adenosylmethionine - universal methyl donor essential for 200+ methylation reactions including neurotransmitter synthesis and DNA methylation.

SAMe

SAMe

GNMT uses SAMe to methylate glycine, acting as overflow for excess SAMe

S-Adenosylmethionine - universal methyl donor essential for 200+ methylation reactions including neurotransmitter synthesis and DNA methylation.

GNMT (Glycine N-Methyltransferase) Discussion