Information on EC 2.1.2.1 - glycine hydroxymethyltransferase

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The expected taxonomic range for this enzyme is: Archaea, Bacteria, Eukaryota

EC NUMBER
COMMENTARY hide
2.1.2.1
-
RECOMMENDED NAME
GeneOntology No.
glycine hydroxymethyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
5,10-methylenetetrahydrofolate + glycine + H2O = tetrahydrofolate + L-serine
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydroxymethyl group transfer
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-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of antibiotics
-
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Biosynthesis of secondary metabolites
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Cyanoamino acid metabolism
-
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folate polyglutamylation
folate transformations I
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folate transformations II
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formaldehyde assimilation I (serine pathway)
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glycine betaine degradation I
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glycine betaine degradation II (mammalian)
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glycine biosynthesis I
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glycine metabolism
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Glycine, serine and threonine metabolism
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Glyoxylate and dicarboxylate metabolism
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-
Metabolic pathways
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-
Methane metabolism
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-
Microbial metabolism in diverse environments
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-
N10-formyl-tetrahydrofolate biosynthesis
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One carbon pool by folate
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photorespiration
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purine metabolism
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purine nucleobases degradation II (anaerobic)
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SYSTEMATIC NAME
IUBMB Comments
5,10-methylenetetrahydrofolate:glycine hydroxymethyltransferase
A pyridoxal-phosphate protein. Also catalyses the reaction of glycine with acetaldehyde to form L-threonine, and with 4-trimethylammoniobutanal to form 3-hydroxy-N6,N6,N6-trimethyl-L-lysine.
CAS REGISTRY NUMBER
COMMENTARY hide
9029-83-8
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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-
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
C24
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-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
strain ATCC13032
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-
Manually annotated by BRENDA team
AB strain
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
strain AB90054
-
-
Manually annotated by BRENDA team
Escherichia coli K-12 MG1655
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-
-
Manually annotated by BRENDA team
strain L. Merr. cv. Williams, soybean
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-
Manually annotated by BRENDA team
strain L. Merr. cv. Williams, soybean
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-
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
gene HTH1832
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-
Manually annotated by BRENDA team
gene HTH1832
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-
Manually annotated by BRENDA team
; strain MHOM/IN/80/Dd8
SwissProt
Manually annotated by BRENDA team
Leishmania donovani MHOM/IN/80/Dd8
strain MHOM/IN/80/Dd8
SwissProt
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
Bonnet monkey
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-
Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
Methanothermobacter thermautotrophicum
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-
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Manually annotated by BRENDA team
Pisum sativum Progress 9
-
-
-
Manually annotated by BRENDA team
strainTM4
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-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
Wistar strain
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-
Manually annotated by BRENDA team
strain 3701B
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-
Manually annotated by BRENDA team
strain ATCC VR1471
SwissProt
Manually annotated by BRENDA team
cv. Solara, antisense lines G310-10, G310-16, G310-76, G310-101 and G310-106
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
strain PCC 6803
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Manually annotated by BRENDA team
strains T1 and G3
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Manually annotated by BRENDA team
strain ATCC 1470
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(6S)-tetrahydrofolate + L-serine
5,10-methylenetetrahydrofolate + glycine + H2O
show the reaction diagram
5,10-methenyl-tetrahydropteroyl pentaglutamate + glycine + H2O
5-formyl-tetrahydropteroyl pentaglutamate + L-serine
show the reaction diagram
5,10-methylenetetrahydrofolate + glycine + H2O
tetrahydrofolate + L-Ser
show the reaction diagram
-
the enzyme is a major source of one-carbon units for cellular metabolism. Potential for disruption of SHMT-mediated one-carbon metabolism by inadequate vitamin B-6 intake
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-
r
5,10-methylenetetrahydrofolate + glycine + H2O
tetrahydrofolate + L-serine
show the reaction diagram
5,6,7,8-tetrahydrofolate + L-Ser
5,10-methylenetetrahydrofolate + glycine + H2O
show the reaction diagram
-
-
-
-
r
alpha-methylserine + tetrahydrofolate
D-alanine + 5,10-methylenetetrahydrofolate
show the reaction diagram
D-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
show the reaction diagram
L-Ser + tetrahydrofolate
Gly + 5,10-methylenetetrahydrofolate
show the reaction diagram
L-Ser + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
show the reaction diagram
L-serine + modified folate
glycine + modified methylenefolate
show the reaction diagram
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
show the reaction diagram
L-serine + tetrahydropteroylglutamate
glycine + 5,10-methylene-tetrahydropteroylglutamate + H2O
show the reaction diagram
NADH + coenzyme Q10
?
show the reaction diagram
tetrahydrofolate + L-Ser
5,10-methylenetetrahydrofolate + glycine
show the reaction diagram
tetrahydrofolate + L-Ser
? + glycine + H2O
show the reaction diagram
-
-
-
-
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tetrahydrofolate + L-serine
5,10-methylenetetrahydrofolate + glycine + H2O
show the reaction diagram
tetrahydromethanopterin + L-Ser
glycine + ?
show the reaction diagram
-
-
-
-
?
tetrahydropteroylglutamate + L-Ser
glycine + ?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
5,10-methylenetetrahydrofolate + glycine + H2O
tetrahydrofolate + L-Ser
show the reaction diagram
-
the enzyme is a major source of one-carbon units for cellular metabolism. Potential for disruption of SHMT-mediated one-carbon metabolism by inadequate vitamin B-6 intake
-
-
r
5,10-methylenetetrahydrofolate + glycine + H2O
tetrahydrofolate + L-serine
show the reaction diagram
L-Ser + tetrahydrofolate
Gly + 5,10-methylenetetrahydrofolate
show the reaction diagram
-
placental conversion of serine to glycine is a major source of fetal glycine
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-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
show the reaction diagram
L-serine + tetrahydropteroylglutamate
glycine + 5,10-methylene-tetrahydropteroylglutamate + H2O
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
tetrahydrofolate
Tetrahydrofolate derivatives
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requirement, if L-serine is substrate
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zinc
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within a mimosine-responsive transcriptional element localized within the first 50 base pairs of the human SHMT1 promoter, 50-base-pair sequence contains a consensus zinc-sensing metal regulatory element at position -44 to -38
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
2,2'-dipyridyl
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2-aminoalanine
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2-aminoisobutyrate
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2-mercaptopropionic acid
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4-chloro-L-threonine
5,10-methenyltetrahydrofolate
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5,10-methylene-5,6,7,8-tetrahydrofolic acid
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5,5-dithiobis(2-nitrobenzoic acid)
5-formyltetrahydrofolate
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can inhibit SHMT in vivo and thereby influence glycine pool size, can accumulate glycine in both wild-type and 5-CHO-THF cycloligase mutant
5-formyltetrahydrofolate monoglutamate
5-methyl-5,6,7,8-tetrahydrofolate
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5-methyltetrahydrofolate monoglutamate
5-Methyltetrahydrofolate triglutamate
allothreonine
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aminoisobutyrate
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-
aminopterin
Antibodies to cytosolic enzyme
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Antibodies to mitochondrial enzyme
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no inhibition of cytosolic enzyme
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beta-Alanine
beta-Aminoalanine
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beta-chloroalanine
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suicide substrate
beta-trifluoroallothreonine
beta-trifluorothreonine
Bromopyruvate
carboxymethoxylamine
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strong
Chloroacetaldehyde
Cibacron blue F3GA
D-alanine
D-beta-Fluoroalanine
D-cycloserine
Dichloromethotrexate
dihydrofolate
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DL-2-methylserine
DL-allothreonine
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DL-O-Methylserine
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Glycidaldehyde
glycine
guanidine hydrochloride
86% loss of activity at 0.25 M
iodoacetamide
L-alanine
L-alpha,beta-diaminopropionic acid
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-
L-amino acids
L-cysteine
L-methionine
L-mimosine
-
inhibits SHMT1 transcription by chelating zinc, eliminates the metal regulatory element- and Sp1-binding activity in nuclear extracts from MCF-7 cells, but not in nuclear extracts from the mimosine-resistant cell line, MCF-7/2a
L-serine
L-threonine
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-
leucovorin
leucovorin (N5-CHO-THF) exhibits a differential inhibition pattern: it significantly inhibits the aldol cleavage of serine catalyzed by zebrafish cytosolic SHMT but it inhibits to a lesser extent the reaction catalyzed by the mitochondrial isozyme. Approximately 70% and 30% inhibition are observed for zebrafish cytosolic- and zebrafish mitochondrial SHMT activities, respectively, in the presence of 70 mM leucovorin. An even larger difference between both isoenzymes is observed when the inhibition is assayed in the presence of 50 mM serine; leucovorin (N5-CHO-THF) exhibits a differential inhibition pattern: it significantly inhibits the aldol cleavage of serine catalyzed by zebrafish cytosolic SHMT but it inhibits to a lesser extent the reaction catalyzed by the mitochondrial isozyme. Approximately 70% and 30% inhibition are observed for zebrafish cytosolic- and zebrafish mitochondrial SHMT activities, respectively, in the presence of 70 mM leucovorin. An even larger difference between both isoenzymes is observed when the inhibition is assayed in the presence of 50 mM serine
methotrexate
methyl methanethiosulfonate
N-ethylmaleimide
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NAD+
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negative effector
O-phosphoserine
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permetrexed
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phenylhydrazine
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partially reversible by pyridoxal 5'-phosphate
pyrimethamine
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S-adenosyl-L-methionine
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Sodium borohydride
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substituted hydroxylamine derivates
sulfonyl fluoride triazine derivates
tetrahydrofolate
Tetrahydrofolate derivatives
tetrahydropteroylglutamate
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Thiosemicarbazide
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5,6,7,8-tetrahydrofolate
-
control of SHMT activity by the availability of 5,6,7,8-tetrahydrofolate
L-serine
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stabilizes the dimeric form of the enzyme
pyridoxal 5'-phosphate
pyridoxal phosphate
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-
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.002
(6S)-tetrahydrofolate
-
pH 7.2, 37C
0.071 - 47
D-serine
0.68
glycine
-
pH 7.5, 70C
0.13 - 11.2
L-Ser
0.14 - 65.3
L-serine
0.43 - 1.6
serine
0.0037 - 3.4
tetrahydrofolate
0.1
tetrahydromethanopterin
-
pH 7.4, 37C
additional information
additional information