Serine hydroxymethyltransferase

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serine hydroxymethyltransferase 1 (soluble)
Identifiers
SymbolSHMT1
Entrez6470
HUGO10850
OMIM182144
RefSeqNM_148918
UniProtP34896
Other data
LocusChr. 17 p11.2
serine hydroxymethyltransferase 2 (mitochondrial)
Identifiers
SymbolSHMT2
Alt. symbolsSHMT
Entrez6472
HUGO10852
OMIM138450
RefSeqNM_005412
UniProtP34897
Other data
EC number2.1.2.1
LocusChr. 12 q12-q14

Serine hydroxymethyltransferase (SHMT) is an enzyme (EC 2.1.2.1) 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 5,6,7,8-tetrahydrofolate to 5,10-methylenetetrahydrofolate (hydrolysis).[1] This reaction provides the largest part of the one-carbon units available to the cell.[2]

Isoforms

Bacteria such as Escherichia coli and Bacillus stearothermophilus have versions of this enzyme and there appear to be two isoforms of SHMT in mammals, one in the cytoplasm (cSHMT) and another in the mitochondria (mSHMT).[1] Plants may have an additional SHMT isoform within chloroplasts[3]

Other reactions

As well as its primary role in folate metabolism, SHMT also catabolyzes other reactions that may be biologically significant, including the conversion of 5,10-methenyltetrahydrofolate to 10-formyltetrahydrofolate.[2] When coupled with C1-tetrahydrofolate synthase and tetrahydropteroate, cSHMT also catalyzes the conversion of formate to serine.[2]

Role in Smith-Magenis syndrome

Smith-Magenis syndrome (SMS) is a rare disorder that manifests as a complex set of traits including facial abnormalities, unusual behaviors, and developmental delay.[4] 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.[4] 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.[4]

References

  1. 1.0 1.1 Rao, N.A., Ambili, M., Jala V.R., Subramanya, H.S. Savithri, H.S. 2003. Structure-function relationship in serine hydroxymethyltransferase. Biochimica et Biophysica Acta 1647: 24-29
  2. 2.0 2.1 2.2 Stover, P., Schirch, V. 1990 Serine hydroxymethyltransferase catalyzes the hydrolysis of 5,10-methylenyltetrahydrofolate to 5-formyltetrahydrofolate. Journal of Biological Chemistry 265(24): 14227-14233
  3. 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: 665-673
  4. 4.0 4.1 4.2 Elsea, S.H., Juyal, R.C., Jiralerspong, S., Finucane, B.M., Pandolfo, M., Greenberg, F., Baldini, A., Stover, P., Patel P.I. 1995. Haploinsufficiency of cytosolic serine hydroxymethyltransferase in the Smith-Magenis syndrome. Am. J. Hum. Genet. 57:1342-1350

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