Serine hydroxymethyltransferase
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 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]
In mammals, the enzyme is a tetramer of four identical subunits of approximately 50,000 Daltons each. The intact holoenzyme has a molecular weight of approximately 200,000 Daltons and incorporates four molecules of pyridoxal phosphate (Vitamin B6) as a coenzyme.[4]
Other reactions
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.[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.[5] 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.[5] 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.[5]
References
- ^ a b Appaji Rao N, Ambili M, Jala VR, Subramanya HS, Savithri HS (April 2003). "Structure-function relationship in serine hydroxymethyltransferase". Biochim. Biophys. Acta 1647 (1–2): 24–9. PMID 12686103.
- ^ a b c Stover P, Schirch V (August 1990). "Serine hydroxymethyltransferase catalyzes the hydrolysis of 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate". J. Biol. Chem. 265 (24): 14227–33. PMID 2201683.
- ^ 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". Biochemistry 11 (9): 1613–5. doi:10.1021/bi00759a011. PMID 5028104.
- ^ a b c Elsea SH, Juyal RC, Jiralerspong S, Finucane BM, Pandolfo M, Greenberg F, Baldini A, Stover P, Patel PI (December 1995). "Haploinsufficiency of cytosolic serine hydroxymethyltransferase in the Smith-Magenis syndrome". Am. J. Hum. Genet. 57 (6): 1342–50. PMC 1801426. PMID 8533763. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1801426.
External links
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| 2.1.1: Methyl- |
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2.1.2: Hydroxymethyl-,
Formyl- and Related |
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| 2.1.3: Carboxy- and Carbamoyl |
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| 2.1.4: Amidino |
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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noco, nuvi, sysi/epon, met
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