SHMT (Serine Hydroxymethyltransferase)
Enzyme interconverting serine and glycine; major source of one-carbon units for folate pool; B6 dependent.
Serine Hydroxymethyltransferase (SHMT) catalyzes the reversible conversion of serine to glycine, transferring a one-carbon unit to tetrahydrofolate (THF) to form 5,10-methyleneTHF. This reaction is a major source of one-carbon units for nucleotide synthesis and methylation.
There are two isoforms: SHMT1 (cytoplasmic) and SHMT2 (mitochondrial). SHMT requires pyridoxal-5'-phosphate (PLP, active B6) as a cofactor.
The mitochondrial SHMT2 is essential for formate production supporting cytoplasmic one-carbon metabolism.
SHMT connects amino acid metabolism (serine/glycine) to the folate cycle and is critical for rapidly dividing cells that need nucleotides.
Cancer cells often upregulate SHMT to support proliferation.
Metabolic Connections
SHMT (Serine Hydroxymethyltransferase) connects to 11 other pathways.
Cofactors
5-MTHF (5-Methyltetrahydrofolate)
One-carbon units from SHMT ultimately contribute to 5-MTHF pool via MTHFR
Primary circulating folate; methyl donor for homocysteine remethylation via MTR; product of MTHFR.
THF (Tetrahydrofolate)
SHMT uses THF as acceptor for one-carbon unit from serine
Active form of folate; carrier of one-carbon units; essential for nucleotide synthesis and methylation.
THF (Tetrahydrofolate)
SHMT transfers one-carbon units between serine/glycine and THF
Active form of folate; carrier of one-carbon units; essential for nucleotide synthesis and methylation.
B Vitamins
B6
B6 (PLP) is required for SHMT catalysis
Pyridoxine - essential for over 100 enzyme reactions including neurotransmitter synthesis and transsulfuration.
B6
B6 is required for SHMT to interconvert serine and glycine
Pyridoxine - essential for over 100 enzyme reactions including neurotransmitter synthesis and transsulfuration.
Folate
SHMT transfers one-carbon units to/from the folate pool
Vitamin B9 - essential for DNA synthesis, methylation, and cell division. Critical during pregnancy for neural tube development.
Folate
SHMT transfers one-carbon units between serine/glycine and folate pool
Vitamin B9 - essential for DNA synthesis, methylation, and cell division. Critical during pregnancy for neural tube development.
Amino Acids
Glycine
Glycine is produced from serine by SHMT; reaction is reversible
Simplest amino acid with diverse roles - glutathione component, collagen synthesis, neurotransmission, and methylation.
Glycine
SHMT converts serine to glycine while donating one-carbon unit to THF
Simplest amino acid with diverse roles - glutathione component, collagen synthesis, neurotransmission, and methylation.
Serine
SHMT converts serine to glycine
Non-essential amino acid; substrate for cystathionine synthesis; precursor for glycine, sphingolipids, and phospholipids.
Serine
SHMT interconverts serine and glycine while transferring one-carbon units
Non-essential amino acid; substrate for cystathionine synthesis; precursor for glycine, sphingolipids, and phospholipids.