- 関
- serine hydroxymethyltransferase
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/17 19:05:58」(JST)
[Wiki en表示]
| 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 |
| 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 tetrahydrofolate to 5,10-methylenetetrahydrofolate (hydrolysis).[1] This reaction provides the largest part of the one-carbon units available to the cell.[2]
Contents
- 1 Isoforms
- 2 Other reactions
- 3 Role in Smith-Magenis syndrome
- 4 References
- 5 External links
Isoforms[edit]
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[edit]
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[edit]
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[edit]
- ^ 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.
External links[edit]
- Serine Hydroxymethyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)
|
Transferase: one carbon transferases (EC 2.1)
|
|
| 2.1.1: Methyl- |
| N- |
- Histamine N-methyltransferase
- Phenylethanolamine N-methyltransferase
- Amine N-methyltransferase
- Phosphatidylethanolamine N-methyltransferase
|
|
| O- |
- 5-hydroxyindole-O-methyltransferase/Acetylserotonin O-methyltransferase
- Catechol-O-methyl transferase
|
|
| Homocysteine |
- Betaine-homocysteine methyltransferase
- Homocysteine methyltransferase
- Methionine synthase
|
|
| Other |
- Phosphatidyl ethanolamine methyltransferase
- DNMT3B
- Histone methyltransferase
- Thymidylate synthase
- DNA methyltransferase
- Thiopurine methyltransferase
|
|
|
2.1.2: Hydroxymethyl-,
Formyl- and Related |
| Hydroxymethyltransferase |
- Serine hydroxymethyltransferase
- 3-methyl-2-oxobutanoate hydroxymethyltransferase
|
|
| Formyltransferase |
- Phosphoribosylglycinamide formyltransferase
- Inosine monophosphate synthase
|
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| Other |
- Glutamate formimidoyltransferase
- Aminomethyltransferase
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|
| 2.1.3: Carboxy- and Carbamoyl |
| Carboxy |
- methylmalonyl-CoA carboxytransferase
|
|
| Carbamoyl |
- Aspartate carbamoyltransferase
- Ornithine carbamoyltransferase
- Oxamate carbamoyltransferase
- Putrescine carbamoyltransferase
- 3-hydroxymethylcephem carbamoyltransferase
- Lysine carbamoyltransferase
- N-acetylornithine carbamoyltransferase
|
|
|
| 2.1.4: Amidino |
- Arginine:glycine amidinotransferase
|
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- B
- enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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Metabolism: amino acid metabolism · synthesis and catabolism enzymes (essential in CAPS)
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| K→acetyl-CoA |
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LYSINE→
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- Saccharopine dehydrogenase
- Glutaryl-CoA dehydrogenase
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LEUCINE→
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- Branched chain aminotransferase
- Branched-chain alpha-keto acid dehydrogenase complex
- Isovaleryl coenzyme A dehydrogenase
- Methylcrotonyl-CoA carboxylase
- Methylglutaconyl-CoA hydratase
- 3-hydroxy-3-methylglutaryl-CoA lyase
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TRYPTOPHAN→
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- Indoleamine 2,3-dioxygenase/Tryptophan 2,3-dioxygenase
- Arylformamidase
- Kynureninase
- 3-hydroxyanthranilate oxidase
- Aminocarboxymuconate-semialdehyde decarboxylase
- Aminomuconate-semialdehyde dehydrogenase
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PHENYLALANINE→tyrosine→
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(see below)
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| G |
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G→pyruvate
→citrate
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glycine→serine→
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- Serine hydroxymethyltransferase
- Serine dehydratase
- glycine→creatine: Guanidinoacetate N-methyltransferase
- Creatine kinase
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alanine→
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cysteine→
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threonine→
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- L-threonine dehydrogenase
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G→glutamate→
α-ketoglutarate
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HISTIDINE→
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- Histidine ammonia-lyase
- Urocanate hydratase
- Formiminotransferase cyclodeaminase
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proline→
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- Proline oxidase
- Pyrroline-5-carboxylate reductase
- 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1
- PYCR1
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arginine→
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- Ornithine aminotransferase
- Ornithine decarboxylase
- Agmatinase
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→alpha-ketoglutarate→TCA
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Other
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- cysteine+glutamate→glutathione: Gamma-glutamylcysteine synthetase
- Glutathione synthetase
- Gamma-glutamyl transpeptidase
- glutamate→glutamine: Glutamine synthetase
- Glutaminase
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|
|
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G→propionyl-CoA→
succinyl-CoA
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VALINE→
|
- Branched chain aminotransferase
- Branched-chain alpha-keto acid dehydrogenase complex
- Enoyl-CoA hydratase
- 3-hydroxyisobutyryl-CoA hydrolase
- 3-hydroxyisobutyrate dehydrogenase
- Methylmalonate semialdehyde dehydrogenase
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ISOLEUCINE→
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- Branched chain aminotransferase
- Branched-chain alpha-keto acid dehydrogenase complex
- 3-hydroxy-2-methylbutyryl-CoA dehydrogenase
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METHIONINE→
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- generation of homocysteine: Methionine adenosyltransferase
- Adenosylhomocysteinase
- regeneration of methionine: Methionine synthase/Homocysteine methyltransferase
- Betaine-homocysteine methyltransferase
- conversion to cysteine: Cystathionine beta synthase
- Cystathionine gamma-lyase
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THREONINE→
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→succinyl-CoA→TCA
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- Propionyl-CoA carboxylase
- Methylmalonyl CoA epimerase
- Methylmalonyl-CoA mutase
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G→fumarate
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PHENYLALANINE→tyrosine→
|
- Phenylalanine hydroxylase
- Tyrosine aminotransferase
- 4-Hydroxyphenylpyruvate dioxygenase
- Homogentisate 1,2-dioxygenase
- Fumarylacetoacetate hydrolase
- tyrosine→melanin: Tyrosinase
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G→oxaloacetate
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asparagine→aspartate→
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- Asparaginase/Asparagine synthetase
- Aspartate transaminase
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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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Metabolism of vitamins, coenzymes, and cofactors
|
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| Fat soluble vitamins |
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Vitamin A
|
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Vitamin E
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- Alpha-tocopherol transfer protein
|
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Vitamin D
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- liver (Sterol 27-hydroxylase or CYP27A1)
- renal (25-Hydroxyvitamin D3 1-alpha-hydroxylase or CYP27B1)
- degradation (1,25-Dihydroxyvitamin D3 24-hydroxylase or CYP24A1)
|
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Vitamin K
|
- Vitamin K epoxide reductase
|
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| Water soluble vitamins |
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Thiamine (B1)
|
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Niacin (B3)
|
- Indoleamine 2,3-dioxygenase
- Formamidase
|
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Pantothenic acid (B5)
|
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Folic acid (B9)
|
- Dihydropteroate synthase
- Dihydrofolate reductase
- Serine hydroxymethyltransferase
|
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- Methylenetetrahydrofolate reductase
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Vitamin B12
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Vitamin C
|
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Riboflavin (B2)
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| Nonvitamin cofactors |
|
Tetrahydrobiopterin
|
- GTP cyclohydrolase I
- 6-pyruvoyltetrahydropterin synthase
- Sepiapterin reductase
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Molybdenum cofactor
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noco, nuvi, sysi/epon, met
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Glycinergics
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Receptor
ligands |
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Agonists
|
- Alanine
- Cycloserine
- Dimethylglycine
- Glycine
- Hypotaurine
- Methylglycine (Sarcosine)
- Milacemide
- Quisqualamine
- Serine
- Taurine
- Trimethylglycine (Betaine)
|
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Antagonists
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- Bicuculline
- Brucine
- Caffeine
- Picrotoxin
- Pitrazepin
- Strychnine
- Thiocolchicoside
- Tutin
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Reuptake
inhibitors |
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Plasmalemmal
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GlyT1 inhibitors
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Ethanol
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GlyT2 inhibitors
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Ethanol
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Vesicular
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Enzyme
inhibitors |
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Anabolism/Catabolism
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SHMT Inhibitors
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GDC Inhibitors
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DAAO Inhibitors
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| Others |
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Precursors
|
- 3-Phosphoglyceric acid
- Serine
|
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Cofactors
|
- Vitamin B6 (Pyridoxine
- pyridoxamine
- pyridoxal → pyridoxal phosphate)
|
|
|
English Journal
- Engineering of high yield production of L-serine in Escherichia coli.
- Mundhada H1, Schneider K1, Christensen HB1, Nielsen AT2.
- Biotechnology and bioengineering.Biotechnol Bioeng.2016 Apr;113(4):807-16. doi: 10.1002/bit.25844. Epub 2015 Oct 7.
- L-serine is a widely used amino acid that has been proposed as a potential building block biochemical. The high theoretical yield from glucose makes a fermentation based production attractive. In order to achieve this goal, serine degradation to pyruvate and glycine in E. coli MG1655 was prevented b
- PMID 26416585
- Elucidation of salt-tolerance metabolic pathways in contrasting rice genotypes and their segregating progenies.
- Mishra P1,2, Mishra V1, Takabe T3, Rai V1, Singh NK4.
- Plant cell reports.Plant Cell Rep.2016 Jun;35(6):1273-86. doi: 10.1007/s00299-016-1959-1. Epub 2016 Mar 18.
- KEY MESSAGE: Differentially expressed antioxidant enzymes, amino acids and proteins in contrasting rice genotypes, and co-location of their genes in the QTLs mapped using bi-parental population, indicated their role in salt tolerance. Soil salinity is a major environmental constraint limiting rice p
- PMID 26993328
- MTHFD1 regulates nuclear de novo thymidylate biosynthesis and genome stability.
- Field MS1, Kamynina E1, Stover PJ2.
- Biochimie.Biochimie.2016 Feb 4. pii: S0300-9084(16)00044-4. doi: 10.1016/j.biochi.2016.02.001. [Epub ahead of print]
- Disruptions in folate-mediated one-carbon metabolism (FOCM) are associated with risk for several pathologies including developmental anomalies such as neural tube defects and congenital heart defects, diseases of aging including cognitive decline, neurodegeneration and epithelial cancers, and hemato
- PMID 26853819
Japanese Journal
- 統合失調症グルタミン酸仮説におけるSHMT1遺伝子
- 吉川 武男,前川 素子,大西 哲生,橋本 謙二,渡邊 明子
- 日本神経精神薬理学雑誌 = Japanese journal of psychopharmacology 30(5), 197-200, 2010-11-25
- NAID 10029093738
- Is mutated serine hydroxymethyltransferase (SHMT) involved in the etiology of neural tube defects?
- ラット肝臓セリンヒドロキシメチル転移酵素の立体化学的特異性
- 山本 信弘,阪本 正子,増田 務
- 大阪教育大学紀要. 第III部門, 自然科学・応用科学 47(1), 125-134, 1998-08
- … 1) ラット肝のs-SHMT, m-SHMTは両者のホロ酵素は280nm, 340nm, 415～420nm付近にピークを持つ吸収スペクトルを示した。 … 2) s-SHMTに対するL-及びD-アミノ酸の阻害作用は，L-及びD-アミノ酸とも，β-炭素原子に-SH基, -OH基等親水性基側鎖にもつものが効果的であった。 …
- NAID 110000561435
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