Serine hydroxymethyltransferase (SHMT) is an enzyme (EC188.8.131.52) which plays an important role in cellular one-carbon pathways by catalyzing the reversible, simultaneous conversions of L-serine to glycine (retro-aldol cleavage) and tetrahydrofolate to 5,10-methylenetetrahydrofolate (hydrolysis). This reaction provides the largest part of the one-carbon units available to the cell.
As well as its primary role in folate metabolism, SHMT also catalyzes other reactions that may be biologically significant, including the conversion of 5,10-methenyltetrahydrofolate to 10-formyltetrahydrofolate. When coupled with C1-tetrahydrofolate synthase and tetrahydropteroate, cSHMT also catalyzes the conversion of formate to serine.
Smith-Magenis syndrome (SMS) is a rare disorder that manifests as a complex set of traits including facial abnormalities, unusual behaviors, and developmental delay. It results from an interstital deletion within chromosome 17p11.2, including the cSHMT gene and a small study showed SHMT activity in SMS patients was ~50% of normal. Reduced SHMT would result in less glycine which could affect the nervous system by acting as an agonist to the NMDA receptor and this could be a mechanism behind SMS.
^ abAppaji Rao N, Ambili M, Jala VR, Subramanya HS, Savithri HS (April 2003). "Structure-function relationship in serine hydroxymethyltransferase". Biochim. Biophys. Acta1647 (1–2): 24–9. doi:10.1016/s1570-9639(03)00043-8. PMID12686103.
^ abcStover P, Schirch V (August 1990). "Serine hydroxymethyltransferase catalyzes the hydrolysis of 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate". J. Biol. Chem.265 (24): 14227–33. PMID2201683.
^Besson V, Nauburger M, Rebeille F, Douce R (1995). "Evidence for three serine hydroxymethyltransferases in green leaf cells. Purification and characterization of the mitochondrial and chloroplastic isoforms". Plant Physiol. Biochem.33 (6): 665–673.
^Martinez-Carrion M, Critz W, Quashnock J (April 1972). "Molecular weight and subunits of serine transhydroxymethylase". Biochemistry11 (9): 1613–5. doi:10.1021/bi00759a011. PMID5028104.