Any feedback?
Information on EC 3.5.3.18 - dimethylargininase and Organism(s) Rattus norvegicus and UniProt Accession O08557
for references in articles please use BRENDA:EC3.5.3.18Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
3.5.3.18 dimethylargininaseIUBMB Comments
Also acts on Nomega-methyl-L-arginine.
Specify your search results
Word Map
- 3.5.3.18
- endothelial
- cardiovascular
- artery
- hypertension
- angiotensin
- l-citrulline
- aortic
-
umbilical
-
vasodilation
- vein
-
endothelium-dependent
- dimethylamine
- atherosclerosis
- coronary
-
methylarginines
- ng,ng-dimethylarginine
- homocysteine
- medicine
- huvecs
-
endothelium-derived
- hyperhomocysteinemia
- nnos
-
l-nmma
-
ii-induced
- ng-monomethyl-l-arginine
-
monomethylarginine
-
ox-ldl
- analysis
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
ddah1, dimethylarginine dimethylaminohydrolase, ddah2, ddah-1, ddah-2, dimethylaminohydrolase, dimethylarginine dimethylaminohydrolase 1, dimethylargininase, human ddah-1, ddah-i, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
DDAH
DDAH-2
DDAHI
-
-
-
-
DDAHII
-
-
-
-
Dimethylargininase
-
-
-
-
dimethylarginine dimethylaminohydrolase
G6a
-
-
-
-
DDAH
-
-
-
-
dimethylarginine dimethylaminohydrolase
-
-
-
-
dimethylarginine dimethylaminohydrolase
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of linear amidines
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
Nomega,Nomega'-dimethyl-L-arginine dimethylamidohydrolase
Also acts on Nomega-methyl-L-arginine.
CAS REGISTRY NUMBER
COMMENTARY
123644-75-7
-
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
dimethyl-L-arginine + H2O
L-citrulline + dimethylamine
-
-
-
?
Ngamma-monomethyl-L-arginine + H2O
L-citrulline + methylamine
-
-
-
?
S-methyl-L-thiocitrulline + H2O
L-citrulline + methanethiol
-
-
-
?
dimethyl-L-arginine + H2O
L-citrulline + dimethylamine
-
-
-
?
NG,NG-dimethyl-L-homoarginine + H2O
?
-
at 2.8% of the activity with NG,NG-dimethyl-L-arginine
-
-
?
NG-monomethyl-L-arginine + H2O
citrulline + methylamine
-
at 61% of the activity with NG,NG-dimethyl-L-arginine
-
-
?
Ngamma-monomethyl-L-arginine + H2O
L-citrulline + methylamine
-
-
-
?
S-methyl-L-thiocitrulline + H2O
L-citrulline + methanethiol
-
-
-
?
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
-
-
-
?
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
-
-
ir
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
-
-
?
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
enzyme plays an integral role in arginine handling
-
-
?
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
enzyme plays a role in metabolism of NG,NG-dimethyl-L-arginine
-
-
?
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
the enzyme plays a functional role in the regulation of nitric oxide synthase
-
-
?
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
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
enzyme plays an integral role in arginine handling
-
-
?
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
enzyme plays a role in metabolism of NG,NG-dimethyl-L-arginine
-
-
?
NG,NG-dimethyl-L-arginine + H2O
dimethylamine + L-citrulline
-
the enzyme plays a functional role in the regulation of nitric oxide synthase
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-(N,N-dimethylamino)diazenolate-2-oxide
1 mM, 50% inhibition of DDAH-1
N-(2-methoxyethyl)-L-arginine
complete inhibition at 100 microM
S-2-amino-4-[N-(2-methoxyethyl)guanidino]butanoic acid benzyl ester
-
aprotinin inhibitor
-
NG,NG-dimethyl-L-arginine release from freeze-thaw whole blood 34% inhibited
-
leupeptin
-
NG,NG-dimethyl-L-arginine release from freeze-thaw whole blood 55% inhibited
lysophosphatidylcholine
-
activity is significantly decreased in cells treated with lysophosphatidylcholine (0.005 mg/ml) for 48 h, 0.001-0.005 mM probucol or 0.001 mM pyrrolidindithiocarbamate significantly attenuate inhibition of DDAH activity by lysophosphatidylcholine
monocrotaline
-
DDAH activity and DDAH1, but not DDAH2, protein expression are significantly reduced after 60mg/kg monocrotaline treatment
N-(2-methoxyethyl)-L-arginine
complete inhibition at 100 microM
oxidized-low density lipoprotein
-
activity is significantly decreased in cells treated with oxidized-low density lipoprotein (0.1 mg/ml) for 48 h, 0.001-0.005 mM probucol or 0.001 mM pyrrolidindithiocarbamat significantly attenuate inhibition of DDAH activity by oxidized-low density lipoprotein
-
PMSF
-
NG,NG-dimethyl-L-arginine release from freeze-thaw whole blood 57% inhibited
protease inhibitor
-
NG,NG-dimethyl-L-arginine release from freeze-thaw whole blood 25-85% inhibited
-
S-2-amino-4-[N-(2-methoxyethyl)guanidino]butanoic acid benzyl ester
-
2-amino-4-(NG-methyl-guanidino)butanoic acid
-
a series of analogues designed, reversible DDAH inhibitors
2-amino-4-(NG-methyl-guanidino)butanoic acid
-
incubation of lysed red blood cells, dose dependent inhibition of NG,NG-dimethyl-L-arginine degradation with the highest dose (1 mM) reversing the pattern to a net increase in NG,NG-dimethyl-L-arginine concentration for the 1- and 3h time points
Zn2+
-
incubation of lysed red blood cells, diminished hydrolyis of NG,NG-dimethyl-L-arginine by addition of physiologically relevant concentrations (0.02 mM)
additional information
-
incubation of lysed red blood cells with EDTA or glucose failed to attenuate the degradation of NG,NG-dimethyl-L-arginine, incubation of whole blood cells with arginine methyltransferase inhibitors does not reduce NG,NG-dimethyl-L-arginine release
-
additional information
-
probucol or pyrrolidindithiocarbamate itself have no effect on the activity of DDAH
-
additional information
-
decrease of DDAH-2 mRNA level induced by 10% serum, ionomycin or endothelial growth factors
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pioglitazone
2-3fold increase of DDAH-2 mRNA and protein levels
interleukin-1beta
2fold increase in DDAH-1 protein expression
-
additional information
-
mRNA expression levels of DDAH-I are not changed in pioglitazone-treated rats
-
additional information
-
increase of DDAH-2 mRNA and protein level induced by SNAP, NOR, 8-bromo-cGMP or CNP
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
-
both DDAHI and DDAHII proteins are detected in peri-infarct cardiomyocytes, while DDAHII immunoreactivity is additionally localized to infiltrating inflammatory cells and blood vessels in the healing infarct. Both plasma and left ventricular concentrations of the DDAH substrate, ADMA, are increased post-myocardial infarction
-
in healthy hearts, DDAHI is absent, and DDAHII is localized to endothelium and endocardium with a similar distribution to that of eNOS
-
DDAHII immunoreactivity is localized to infiltrating inflammatory cells and blood vessels in the healing infarct
-
in the gray matter, especially in the ventral portion and sympathetic ganglion
-
DDAHII immunoreactivity is localized to infiltrating inflammatory cells and blood vessels in the healing infarct
-
entire ventricular zone and tegmentum, ciliarly ganglion, inferior olive, interpeduncular nucleus, red nucleus, dorsal tegmental nucleus and nuclues of the lateral lemniscus
-
in healthy hearts, DDAHI is absent, and DDAHII is localized to endothelium and endocardium with a similar distribution to that of eNOS
-
in healthy hearts, DDAHI is absent, and DDAHII is localized to endothelium and endocardium with a similar distribution to that of eNOS
expression of mRNA for DDAH-1 is 7fold higher in the liver compared to DDAH-2
expression of mRNA for DDAH-1 is 2fold higher in the renal cortex compared to DDAH-2
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). DDAH1_RAT
285
0
31426
Swiss-Prot
Mitochondrion (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
34000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-30°C, 0.1 M sodium phosphate buffer, pH 7.0, 10% glycerol, 1 mM 2-mercaptoethanol
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
following myocardial infarction, left ventricular DDAH activity is increased to 210% of control
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
influence on atherosclerosis in experimental models by increased ADMA concentrations and reduced NO synthesis
medicine
medicine
-
DDAH activity and elevated endogenous asymmetric dimethylarginine is implicated in endothelial dysfunction exposed to glycosylated bovine serum albumin, aminoguanidine can protect endothelium against injury induced by glycosylated bovine serum albumin both in vitro and in vivo
medicine
-
endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (hydrolyzed by DDAH) is elevated in many patients and may contribute to the initiation and progression of their disease
medicine
-
in vivo administration of DDAH inhibitors (2-amino-4-(NG-methyl-guanidino)butanoic acid and its analogues) increases plasma NG,NG-dimethyl-L-arginine levels, giving proof of concept that these can be used to probe the physiological effects of DDAH inhibition, with potential for pharmaceutical use of DDAH inhibitors in diseases where excess NO production is implicated
medicine
influence on atherosclerosis in experimental models by increased ADMA concentrations and reduced NO synthesis
medicine
-
seven days after coronary artery ligation, L-Arg and methylated arginine content, as well as DDAH activity are determined in homogenates of left ventricular infarct and border. In healthy hearts, DDAHI is absent, and DDAHII is localized to endothelium and endocardium with a similar distribution to that of eNOS. Following myocardial infarction, left ventricular DDAH activity is increased to 210% of control. Both DDAHI and DDAHII proteins are detected in peri-infarct cardiomyocytes, while DDAHII immunoreactivity is additionally localized to infiltrating inflammatory cells and blood vessels in the healing infarct. Both plasma and left ventricular concentrations of the DDAH substrate, ADMA, are increased post-myocardial infarction, although the ratio of Arg:ADMA is retained in the left ventricular post-myocardial infarction relative to sham operated controls
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kimoto, M.; Sasakawa, T.; Tsuji, H.; Miyatake, S.; Oka, T.
Cloning and sequencing of cDNA encoding NG,NG-dimethylarginine dimethylaminohydrolase from rat kidnes
Biochim. Biophys. Acta
1337
6-10
1997
Rattus norvegicus
Santa Maria, J.; Vallance, P.; Charles, I.G.; Leiper, J.M.
Identification of microbial dimethylarginine dimethylaminohydrolase enzymes
Mol. Microbiol.
33
1278-1279
1999
Homo sapiens, Mycobacterium tuberculosis, Mus musculus, Pseudomonas aeruginosa, Rattus norvegicus, Streptomyces coelicolor
MacAllister, R.J.; Parry, H.; Kimoto, M.; Ogawa, T.; Russell, R.J.; Hodson, H.; Whiteley, G.St.J.; Vallance, P.
Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase
Br. J. Pharmacol.
119
1533-1540
1996
Homo sapiens, Rattus norvegicus
Ogawa, T.; Kimoto, M.; Sasaoka, K.
Purification and properties of a new enzyme, NG,NG-dimethylarginine dimethylaminohydrolase from rat kidney
J. Biol. Chem.
264
10205-10209
1989
Rattus norvegicus
Kimoto, M.; Tsuji, H.; Ogawa, T.; Sasaoka, K.
Detection of NG,NG-dimethylarginine dimethylaminohydrolase in the nitric oxide-generating systems of rats using monoclonal antibody
Arch. Biochem. Biophys.
300
657-662
1993
Rattus norvegicus
Billecke, S.S.; Kitzmiller, L.A.; Northrup, J.J.; Whitesall, S.E.; Kimoto, M.; Hinz, A.V.; D'Alecy, L.G.
Contribution of whole blood to the control of plasma asymmetrical dimethylarginine
Am. J. Physiol. Heart Circ. Physiol.
291
H1788-1796
2006
Rattus norvegicus
Yin, Q.; Fu, S.; He, P.; Xiong, Y.
Dimethylarginine dimethylaminohydrolase inhibition and asymmetric dimethylarginine accumulation contribute to endothelial dysfunction in rats exposed to glycosylated protein: Effects of aminoguanidine
Atherosclerosis
190
53-61
2006
Rattus norvegicus
Mishima, T.; Hamada, T.; Ui-Tei, K.; Miyata, Y.; Imaki, J.; Suzuki, H.; Yamashita K.
Expression of DDAH1 in chick and rat embryos
Brain Res. Dev. Brain Res.
148
223-232
2004
Gallus gallus, Rattus norvegicus
Jiang, J.L.; Zhang, X.H.; Li, N.S.; Rang, W.Q; Feng-Ye, W.Q.; Hu, C.P.; Li, Y.J.; Deng, H.W.
Probucol decreases asymmetrical dimethylarginine level by alternation of protein arginine methyltransferase I and dimethylarginine dimethylaminohydrolase activity
Cardiovasc. Drugs Ther.
20
281-294
2006
Homo sapiens, Rattus norvegicus
Wakino, S.; Hayashi, K.; Tatematsu, S.; Hasegawa, K.; Takamatsu, I.; Kanda, T.; Homma, K.; Yoshioka, K.; Sugano, N.; Saruta, T.
Pioglitazone lowers systemic asymmetric dimethylarginine by inducing dimethylarginine dimethylaminohydrolase in rats
Hypertens. Res.
28
255-262
2005
Rattus norvegicus
Rossiter, S.; Smith, C.L.; Malaki, M.; Nandi, M.; Gill, H.; Leiper, J.M.; Vallance, P.; Selwood, D.L.
Selective substrate-based inhibitors of mammalian dimethylarginine dimethylaminohydrolase
J. Med. Chem.
48
4670-4678
2005
Rattus norvegicus
Sasaki, A.; Doi, S.; Mizutani, S.; Azuma, H.
Roles of accumulated endogenous nitric oxide synthase inhibitors, enhanced arginase activity, and attenuated nitric oxide synthase activity in endothelial cells for pulmonary hypertension in rats
Am. J. Physiol. Lung Cell Mol. Physiol.
292
L1480-L1487
2007
Rattus norvegicus
Wang, D.; Gill, P.S.; Chabrashvili, T.; Onozato, M.L.; Raggio, J.; Mendonca, M.; Dennehy, K.; Li, M.; Modlinger, P.; Leiper, J.; Vallance, P.; Adler, O.; Leone, A.; Tojo, A.; Welch, W.J.; Wilcox, C.S.
Isoform-specific regulation by N(G),N(G)-dimethylarginine dimethylaminohydrolase of rat serum asymmetric dimethylarginine and vascular endothelium-derived relaxing factor/NO
Circ. Res.
101
627-635
2007
Rattus norvegicus (Q6MG60)
Tain, Y.L.; Baylis, C.
Determination of dimethylarginine dimethylaminohydrolase activity in the kidney
Kidney Int.
72
886-889
2007
Rattus norvegicus
Wadham, C.; Mangoni, A.A.
Dimethylarginine dimethylaminohydrolase regulation: a novel therapeutic target in cardiovascular disease
Expert. Opin. Drug Metab. Toxicol.
5
303-319
2009
Bos taurus, Bos taurus (Q3SX44), Oryctolagus cuniculus, Rattus norvegicus (O08557), Rattus norvegicus (Q6MG60), Homo sapiens (O94760), Homo sapiens (O95865), Mus musculus (Q99LD8), Mus musculus (Q9CWS0)
Sakurada, M.; Shichiri, M.; Imamura, M.; Azuma, H.; Hirata, Y.
Nitric oxide upregulates dimethylarginine dimethylaminohydrolase-2 via cyclic GMP induction in endothelial cells
Hypertension
52
903-909
2008
Homo sapiens, Mus musculus, Rattus norvegicus
EXTERNAL LINKS (specific for EC-Number 3.5.3.18)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
