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Information on EC 1.5.8.4 - dimethylglycine dehydrogenase and Organism(s) Rattus norvegicus and UniProt Accession Q63342
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1.5.8.4 dimethylglycine dehydrogenaseIUBMB Comments
A flavoprotein, containing a histidyl(Npi)-(8alpha)FAD linkage at position 91 in the human protein. An imine intermediate is channeled from the FAD binding site to the 5,6,7,8-tetrahydrofolate binding site through a 40 A tunnel [5,8,9]. In the absence of 5,6,7,8-tetrahydrofolate the enzyme forms formaldehyde [5,9].
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The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
Synonyms
dimethylglycine dehydrogenase, dmgdh, me2glydh, csal_0990, n,n-dimethylglycine oxidase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Me2GlyDH
N,N-dimethylglycine oxidase
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-
-
-
Me2GlyDH
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
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oxidation
-
-
-
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reduction
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-
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oxidative deamination
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-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
N,N-dimethylglycine,5,6,7,8-tetrahydrofolate:electron-transferflavoprotein oxidoreductase (demethylating,5,10-methylenetetrahydrofolate-forming)
A flavoprotein, containing a histidyl(Npi)-(8alpha)FAD linkage at position 91 in the human protein. An imine intermediate is channeled from the FAD binding site to the 5,6,7,8-tetrahydrofolate binding site through a 40 A tunnel [5,8,9]. In the absence of 5,6,7,8-tetrahydrofolate the enzyme forms formaldehyde [5,9].
CAS REGISTRY NUMBER
COMMENTARY
37256-30-7
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
N,N-dimethylglycine + acceptor + H2O
sarcosine + formaldehyde + reduced acceptor
-
-
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
reaction of the choline degradation pathway
-
?
5,10-methenyltetrahydrofolate + FADH2
5,10-methylene tetrahydrofolate + FAD
-
-
-
-
?
epsilon-N-methyl-L-lysine + acceptor + H2O
formaldehyde + L-lysine + reduced acceptor
-
-
-
?
N,N-dimethylglycine + electron-transfer flavoprotein + H2O
sarcosine + formaldehyde + reduced electron-transfer flavoprotein
-
-
-
?
N,N-dimethylglycine + H2O + oxidized 1-methoxy-5-methylphenazinium methylsulfate
sarcosine + formaldehyde + reduced 1-methoxy-5-methylphenazinium methylsulfate
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-
-
-
?
N,N-dimethylglycine + H2O + oxidized 2,6-dichlorophenolindophenol
sarcosine + formaldehyde + reduced 2,6-dichlorophenolindophenol
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-
-
-
?
N,N-dimethylglycine + oxidized ferricenium hexafluorophosphate + H2O
sarcosine + formaldehyde + reduced ferricenium hexafluorophosphate + H2O2
-
-
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
N-methyl-L-alanine + acceptor + H2O
formaldehyde + L-alanine + reduced acceptor
-
-
-
?
sarcosine + acceptor + H2O
glycine + formaldehyde + reduced acceptor
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-
-
?
N,N-dimethylglycine + acceptor + H2O
sarcosine + formaldehyde + reduced acceptor
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acceptors: 2,6-dichlorophenolindophenol, phenazine methosulfate
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?
N,N-dimethylglycine + acceptor + H2O
sarcosine + formaldehyde + reduced acceptor
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acceptors: 2,6-dichlorophenolindophenol, phenazine methosulfate
-
?
N,N-dimethylglycine + acceptor + H2O
sarcosine + formaldehyde + reduced acceptor
-
acceptors: 2,6-dichlorophenolindophenol, phenazine methosulfate
-
?
N,N-dimethylglycine + acceptor + H2O
sarcosine + formaldehyde + reduced acceptor
-
acceptors: 2,6-dichlorophenolindophenol, phenazine methosulfate
-
?
N,N-dimethylglycine + acceptor + H2O
sarcosine + formaldehyde + reduced acceptor
-
acceptors: 2,6-dichlorophenolindophenol, phenazine methosulfate
-
?
N,N-dimethylglycine + acceptor + H2O
sarcosine + formaldehyde + reduced acceptor
-
acceptors: 2,6-dichlorophenolindophenol, phenazine methosulfate
-
?
N,N-dimethylglycine + acceptor + H2O
sarcosine + formaldehyde + reduced acceptor
-
acceptors: 2,6-dichlorophenolindophenol, phenazine methosulfate
-
?
N,N-dimethylglycine + acceptor + H2O
sarcosine + formaldehyde + reduced acceptor
-
acceptors: 2,6-dichlorophenolindophenol, phenazine methosulfate
-
?
N,N-dimethylglycine + acceptor + H2O
sarcosine + formaldehyde + reduced acceptor
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acceptors: 2,6-dichlorophenolindophenol, phenazine methosulfate
-
?
N,N-dimethylglycine + acceptor + H2O
sarcosine + formaldehyde + reduced acceptor
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bound tetrahydrofolate interacts directly with the enzyme and serves as an acceptor for the one-carbon unit produced during the oxidative demethylation of dimethylglycine
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
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during the reaction tightly bound tetrahydropteroylpentaglutamate is converted to 5,10-methylene tetrahydropteroylpentaglutamate
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
during the reaction tightly bound tetrahydropteroylpentaglutamate is converted to 5,10-methylene tetrahydropteroylpentaglutamate
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
during the reaction tightly bound tetrahydropteroylpentaglutamate is converted to 5,10-methylene tetrahydropteroylpentaglutamate
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
during the reaction tightly bound tetrahydropteroylpentaglutamate is converted to 5,10-methylene tetrahydropteroylpentaglutamate
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
reaction of the choline degradation pathway
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
reaction of the choline degradation pathway
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
reaction of the choline degradation pathway
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
reaction of the choline degradation pathway
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
reaction of the choline degradation pathway
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
reaction of the choline degradation pathway
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
tetrahydropteroylpentaglutamate is used in vivo as an acceptor of the one-carbon group generated during the reaction
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
reaction of the choline degradation pathway
-
?
5,10-methenyltetrahydrofolate + FADH2
5,10-methylene tetrahydrofolate + FAD
-
-
-
-
?
N,N-dimethylglycine + electron-transfer flavoprotein + H2O
sarcosine + formaldehyde + reduced electron-transfer flavoprotein
-
-
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
during the reaction tightly bound tetrahydropteroylpentaglutamate is converted to 5,10-methylene tetrahydropteroylpentaglutamate
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
during the reaction tightly bound tetrahydropteroylpentaglutamate is converted to 5,10-methylene tetrahydropteroylpentaglutamate
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
during the reaction tightly bound tetrahydropteroylpentaglutamate is converted to 5,10-methylene tetrahydropteroylpentaglutamate
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
during the reaction tightly bound tetrahydropteroylpentaglutamate is converted to 5,10-methylene tetrahydropteroylpentaglutamate
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
reaction of the choline degradation pathway
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
reaction of the choline degradation pathway
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
reaction of the choline degradation pathway
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
reaction of the choline degradation pathway
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
reaction of the choline degradation pathway
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
reaction of the choline degradation pathway
-
?
N,N-dimethylglycine + tetrahydropteroylpentaglutamate + acceptor
sarcosine + 5,10-methylene tetrahydropteroylpentaglutamate + reduced acceptor
-
tetrahydropteroylpentaglutamate is used in vivo as an acceptor of the one-carbon group generated during the reaction
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
-
covalently bound
FAD
-
covalent attachment of FAD to the apoenzyme proceeds in vitro spontaneously and does not require a mitochondrial protein factor
FAD
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the precursor form of the enzyme is a good substrate for mitochondria-assisted flavinylation reaction, flavinylation of precursor precedes polypeptide processing by the mitochondrial processing peptidase during the biogenesis of holo-enzyme
FAD
-
absolutely required, covalently bound to the apoenzyme via a histidinyl(N3)-(8alpha)FAD linkage, cofactor-free apoenzyme shows 70% reduced activity compared to the holoenzyme
additional information
-
1-methoxy-5-methylphenazinium methylsulfate can act as electron acceptor
-
additional information
-
2,6-dichlorophenolindophenol can act as electron acceptor
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.05
N,N-dimethylglycine
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pH 7.0, 30°C, recombinant holoenzyme, 2 Km-values
9.4
N,N-dimethylglycine
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pH 7.0, 30°C, recombinant holoenzyme, 2 Km-values
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
detectable levels of expression demonstrated at the RNA and protein level
-
detectable levels of expression demonstrated at the RNA and protein level
-
detectable levels of expression demonstrated at the RNA and protein level
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detectable levels of expression demonstrated at the RNA and protein level
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). M2GD_RAT
857
0
96048
Swiss-Prot
Mitochondrion (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
90000
93000
-
x * 90000, native enzyme, SDS-PAGE, x * 93000, recombinant enzyme, SDS-PAGE
90000
-
x * 90000, native enzyme, SDS-PAGE, x * 93000, recombinant enzyme, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 90000, native enzyme, SDS-PAGE, x * 93000, recombinant enzyme, SDS-PAGE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of the recombinant mature and precursor forms of enzyme and the enzyme complexed with 5,6,7,8-tetrahydrofolate. Both forms reveal similar kinetic parameters and have the same tertiary structure fold with two domains formed by N- and C-terminal halves of the protein. The active center is located in the N-terminal domain while the tetrahydrofolate binding site is located in the C-terminal domain about 40 A from the isoalloxazine ring of FAD. The folate binding site is connected with the enzyme active center via an intramolecular channel. This suggests the possible transfer of the intermediate imine of dimethylglycine from the active center to the bound 5,6,7,8-tetrahydrofolate where they can react producing a 5,10-methylenetetrahydrofolate
recombinant mature and precursor forms, in complex with tetrahydrofolate. Both forms of DMGDH reveal similar kinetic parameters and have the same tertiary structure fold with two domains formed by N- and C-terminal halves of the protein. The active center is located in the N-terminal domain while the THF binding site is located in the C-terminal domain about 40 A from the isoalloxazine ring of FAD. The folate binding site is connected with the enzyme active center via an intramolecular channel
using 0.2 M K/Na-tartrate-20% (w/v) PEG 3350 for the mature enzyme or 0.2 M NaSCN-20% (w/v) PEG 3350-0.1 M Tris pH 7.5 for the precursor
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native enzyme from liver mitochondria, recombinant His-tagged enzyme from Escherichia coli 45fold by nickel affinity chromatography
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of in vitro synthesized 6-His-dimethylglycine dehydrogenase on nickel chelating Sepharose
-
using ammonium sulfate treatment and dissolution in 7.5 mM potassium phosphate
-
using gel filtration chromatography on Sephadex G-150, DEAE-cellulose chromatography, and affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells as a C-terminally 6-His-tagged fusion protein which is predominantly in its apo form
screening of a cDNA library prepared in Escherichia coli from rat liver polyA RNA in the plasmid vector peD-X
overexpression in Escherichia coli strain JM109 as N-terminally His-tagged enzyme being equally distributed in the soluble fraction and the insoluble inclusion body fraction
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
refolding by 80fold dilution after solubilization from inclusion bodies by urea treatment, 50-60% reactivation yield, overview
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Porter, D.H.; Cook, R.J.; Wagner, C.
Enzymatic properties of dimethylglycine dehydrogenase and sarcosine dehydrogenase from rat liver
Arch. Biochem. Biophys.
243
396-407
1985
Rattus norvegicus
Cook, R.J.; Misono, K.S.; Wagner, C.
The amino acid sequences of the flavin-peptides of dimethylglycine dehydrogenase and sarcosine dehydrogenase from rat liver mitochondria
J. Biol. Chem.
260
12998-13002
1985
Rattus norvegicus
Wittwer, A.J.; Wagner, C.
Identification of the folate-binding proteins of rat liver mitochondria as dimethylglycine dehydrogenase and sarcosine dehydrogenase. Flavoprotein nature and enzymatic properties of the purified proteins
J. Biol. Chem.
256
4109-4115
1981
Rattus norvegicus
Wittwer, A.J.; Wagner, C.
Identification of the folate-binding proteins of rat liver mitochondria as dimethylglycine dehydrogenase and sarcosine dehydrogenase. Purification and folate-binding characteristics
J. Biol. Chem.
256
4102-4108
1981
Rattus norvegicus
Cook, R.J.; Misono, K.S.; Wagner, C.
Identification of the covalently bound flavin of dimethylglycine dehydrogenase and sarcosine dehydrogenase from rat liver mitochondria
J. Biol. Chem.
259
12475-12480
1980
Rattus norvegicus
Frisell, W.R.; Mackenzie, C.G.
Sarcosine dehydrogenase and dimethylglycine dehydrogenase (rat liver, monkey liver)
Methods Enzymol.
17A
976-981
1970
Macaca mulatta, Rattus norvegicus
-
Frisell, W.R.; Mackenzie, C.G.
Separation and purification of sarcosine dehydrogenase and dimethylglycine dehydrogenase
J. Biol. Chem.
237
94-98
1962
Rattus norvegicus
Wagner, C.; Briggs, W.T.; Cook, R.J.
Covalent binding of folic acid to dimethylglycine dehydrogenase
Arch. Biochem. Biophys.
233
457-461
1984
Rattus norvegicus
Wittwer, A.J.; Wagner, C.
Identification of folate binding protein of mitochondria as dimethylglycine dehydrogenase
Proc. Natl. Acad. Sci. USA
77
4484-4488
1980
Rattus norvegicus
Lang, H.; Polster, M.; Brandsch, R.
Rat liver dimethylglycine dehydrogenase. Flavinylation of the enzyme in hepatocytes in primary culture and characterization of a cDNA clone
Eur. J. Biochem.
198
793-799
1991
Rattus norvegicus (Q63342)
Lang, H.; Minaian, K.; Freudenberg, N.; Hoffmann, R.; Brandsch, R.
Tissue specificity of rat mitochondrial dimethylglycine dehydrogenase expression
Biochem. J.
299
393-398
1994
Rattus norvegicus
-
Otto, A.; Stoltz, M.; Sailer, H.; Brandsch, R.
Biogenesis of the covalently flavinylated mitochondrial enzyme dimethylglycine dehydrogenase
J. Biol. Chem.
271
9823-9829
1996
Rattus norvegicus
Brizio, C.; Otto, A.; Brandsch, R.; Passarella, S.; Barile, M.
A protein factor of rat liver mitochondrial matrix involved in flavinylation of dimethylglycine dehydrogenase
Eur. J. Biochem.
267
4346-4354
2000
Oryctolagus cuniculus, Rattus norvegicus
Brizio, C.; Barile, M.; Brandsch, R.
Flavinylation of the precursor of mitochondrial dimethylglycine dehydrogenase by intact and solubilised mitochondria
FEBS Lett.
522
141-146
2002
Rattus norvegicus
Brizio, C.; Brandsch, R.; Bufano, D.; Pochini, L.; Indiveri, C.; Barile, M.
Over-expression in Escherichia coli, functional characterization and refolding of rat dimethylglycine dehydrogenase
Protein Expr. Purif.
37
434-442
2004
Rattus norvegicus
Brizio, C.; Brandsch, R.; Douka, M.; Wait, R.; Barile, M.
The purified recombinant precursor of rat mitochondrial dimethylglycine dehydrogenase binds FAD via an autocatalytic reaction
Int. J. Biol. Macromol.
42
455-462
2008
Rattus norvegicus (Q63342)
Luka, Z.; Pakhomova, S.; Loukachevitch, L.V.; Newcomer, M.E.; Wagner, C.
Folate in demethylation the crystal structure of the rat dimethylglycine dehydrogenase complexed with tetrahydrofolate
Biochem. Biophys. Res. Commun.
449
392-398
2014
Rattus norvegicus, Rattus norvegicus (Q5RKL4), Rattus norvegicus (Q63342)
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