Serine hydroxymethyltransferase, cytosolic (SHMT1) (SHMT1)

Human serine hydroxymethyltransferase 1 (SHMT1) is a pyridoxal phosphate-dependent enzyme located in the cytoplasm that plays a pivotal role in folate-mediated one-carbon metabolism (UniProt P34896). It catalyzes the reversible conversion of L-serine and tetrahydrofolate into glycine and 5,10-methylene-tetrahydrofolate, providing the essential one-carbon units required for the de novo synthesis of purines and thymidylate (PubMed: 25867061). By regulating the flux of these metabolites, SHMT1 is a critical determinant of DNA synthesis and genomic integrity (PubMed: 19279614). In oncology, SHMT1 is frequently overexpressed to meet the high metabolic demands of proliferating cancer cells, particularly in lung and breast cancers (PubMed: 31462649). Therapeutic strategies often involve the use of antifolates like pemetrexed or novel small-molecule inhibitors such as SHIN1 to disrupt this pathway and inhibit tumor growth (PubMed: 28515139). Beyond cancer, genetic variations in SHMT1 are associated with risks for neural tube defects and cardiovascular diseases due to its influence on homocysteine levels (PubMed: 11133162).

Other names

Serine methylaseGlycine hydroxymethyltransferaseCSHMTSHMT

Inhibition of the reversible conversion of L-serine and tetrahydrofolate to glycine and 5,10-methylene-tetrahydrofolate, thereby depleting the pool of one-carbon units required for de novo purine and thymidylate biosynthesis.