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Serine hydroxymethyltransferase



serine hydroxymethyltransferase 1 (soluble)
Identifiers
Symbol SHMT1
Entrez 6470
HUGO 10850
OMIM 182144
RefSeq NM_148918
UniProt P34896
Other data
Locus Chr. 17 p11.2
serine hydroxymethyltransferase 2 (mitochondrial)
Identifiers
Symbol SHMT2
Alt. Symbols SHMT
Entrez 6472
HUGO 10852
OMIM 138450
RefSeq NM_005412
UniProt P34897
Other data
EC number 2.1.2.1
Locus Chr. 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]

Contents

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. ^ a b 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. ^ a b c 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. ^ a b c 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
v • d • e
Transferase: one carbon transferases (EC 2.1)
2.1.1 - Methyltransferases5-hydroxyindole-O-methyltransferase/Acetylserotonin O-methyltransferase - Betaine-homocysteine methyltransferase - Catechol-O-methyl transferase - Histamine N-methyltransferase - Homocysteine methyltransferase - 5-Methyltetrahydrofolate-homocysteine methyltransferase - Phosphatidyl ethanolamine methyltransferase - Phenylethanolamine N-methyltransferase - DNMT3B - Histone methyltransferase - Thymidylate synthase - Tryptamine N-methyltransferase - DNA methyltransferase
2.1.2 - Hydroxy methyl-, Formyl- and Related TransferasesSerine hydroxymethyltransferase - Phosphoribosylglycinamide formyltransferase - Inosine monophosphate synthase - Glutamate formimidoyltransferase - Aminomethyltransferase
2.1.3 - Carboxy- and Carbamoyl transferasesOrnithine transcarbamylase
2.1.4 - Amidino transferasesArginine:glycine amidinotransferase
v • d • e
Amino acid metabolism enzymes
phenylalanine→tyrosine→fumarate→TCAPhenylalanine hydroxylase - Tyrosine aminotransferase - 4-Hydroxyphenylpyruvate dioxygenase - Homogentisate 1,2-dioxygenase - Fumarylacetoacetate hydrolase
tyrosine→dopamine→epinephrineTyrosine hydroxylase - Aromatic L-amino acid decarboxylase - Dopamine beta hydroxylase - Phenylethanolamine N-methyltransferase
leucine→HMG-CoA (keto)Branched-chain alpha-keto acid dehydrogenase complex - Isovaleryl coenzyme A dehydrogenase - Methylcrotonyl-CoA carboxylase
isoleucine/valine→propionyl-CoABranched-chain alpha-keto acid dehydrogenase complex
methionine→cysteine→propionyl-CoAMethionine adenosyltransferase - Adenosylhomocysteinase - (or MTR) - Cystathionine beta synthase - Cystathionine gamma-lyase
propionyl-CoA→succinyl-CoA→TCAPropionyl-CoA carboxylase - Methylmalonyl-CoA mutase
serine→glycineSerine hydroxymethyltransferase
histidineto histamine: Histidine decarboxylase - to glutamate: Histidine ammonia-lyase - Urocanate hydratase - Formiminotransferase cyclodeaminase
tryptophan→serotonin→melatoninTryptophan hydroxylase - Aromatic L-amino acid decarboxylase - 5-hydroxyindole-O-methyltransferase
asparagine→aspartate→oxaloacetate→TCAAsparaginase/Asparagine synthetase - Aspartate transaminase
glutamateGlutaminase - Glutamate decarboxylase
lysine→ketoSaccharopine dehydrogenase
otherTyrosinase
v • d • e
Metabolism of vitamins, coenzymes, and cofactors
Folic acidDihydropteroate synthetase - Dihydrofolate reductase - Serine hydroxymethyltransferase
Vitamin D25-Hydroxyvitamin D3 1-alpha-Hydroxylase
ThiamineThiamine pyrophosphokinase
Vitamin CL-gulonolactone oxidase
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Serine_hydroxymethyltransferase". A list of authors is available in Wikipedia.
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