Serine hydroxymethyltransferase 2 (SHMT2)

Serine hydroxymethyltransferase 2 (SHMT2) is a mitochondrial, pyridoxal phosphate-dependent enzyme essential for the reversible conversion of serine to glycine, simultaneously transferring a one-carbon group to tetrahydrofolate to generate 5,10-methylenetetrahydrofolate. SHMT2 underpins mitochondrial one-carbon metabolism, critical for nucleotide (purine and thymidylate) biosynthesis, redox control, and cellular proliferation. Overexpression of SHMT2 is observed in numerous cancers, contributing to tumor cell growth and survival, and is associated with poor prognosis in cancer patients. SHMT2 is therefore pursued as a drug target in cancer chemotherapy, especially with antifolate drugs that inhibit its enzymatic activity. This enzyme transitions between dimeric and tetrameric states in mitochondria and is tightly regulated both transcriptionally and post-translationally, with functional roles extending to metabolic signaling and inflammation.

Other names

Mitochondrial serine hydroxymethyltransferaseGlycine hydroxymethyltransferase, mitochondrial

Competitive inhibition of one-carbon transfer activity (antifolates); Blockade of serine to glycine conversion, disrupting nucleotide biosynthesis