3.5.3.18	analysis	use of inhibitor N-(but-3-yn-1-yl)-2-chloroethanimidamide as a broad-specificity probe for labeling endogenous DDAH isoforms and enzymes with similar pharmacophores. Inhibitor labels the active fraction of DDAH-1 in intact mammalian cells and can be blocked by the presence of competitive reversible and irreversible inhibitors. Incorporation of the alkyne tag allows to derivatize with a variety of reagents after in vivo tagging	712238	
3.5.3.18	medicine	2-chloroacetamidine may potentially find wide applicability as a general pharmacophore, useful in delineating characteristics of the amidinotransferase superfamily	664074	
3.5.3.18	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	667365	
3.5.3.18	medicine	DDAH influences insulin sensitivity by regulating the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine	695944	
3.5.3.18	medicine	decreased DDAH-1 expression may cause accumulation of endogenous inhibitors of enothelial NO synthase, thereby contributing to endothelial dysfunction in the failing heart	667155	
3.5.3.18	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	667159	
3.5.3.18	medicine	epoetin beta and darbepoetin alpha posttranslationally impair DDAH activity via increased oxidative stress, causing NG,NG-dimethyl-L-arginine as an important cardiovascular risk factor to accumulate and inhibit NO-synthesis	669059	
3.5.3.18	medicine	expression and secretion of the vascular endothelial growth factor is not increased in DDAH1-transfected cells	667355	
3.5.3.18	medicine	global knockout of Ddah2 results in elevated blood pressure during periods of activity and changes in vascular responsiveness mediated by changes in methylarginine concentration, and systemic nitric oxide concentrations. In a model of severe polymicrobial sepsis, Ddah2 knockout affects outcome. Monocyte-specific deletion of Ddah2 results in a similar pattern of increased severity to that seen in globally deficient animals	752613	
3.5.3.18	medicine	hyperhomocysteinemia is induced in human DDAH1 transgenic mice and wild-type littermates using a high methionine/low folate diet. Plasma total homocysteine is elevated approximately 3fold in both wild-type and DDAH1 transgenic mice fed the high methionine/low folate diet compared with the control diet. Plasma asymmetrical dimethylarginine is approximately 40% lower in DDAH1 transgenic mice compared with wild-type mice irrespective of diet. Responses to 10 microM papaverine, a direct smooth muscle dilator, are impaired with the high methionine/low folate diet in wild-type mice but not DDAH1 transgenic mice. DDAH1 transgenic mice also are protected from hypertrophy of cerebral arterioles but not from accelerated carotid artery thrombosis induced by the high methionine/low folate diet	711765	
3.5.3.18	medicine	in a mouse model of severe malaria, Plasmodium berghei ANKA infection inactivates hepatic DDAH1 via a post-transcriptional mechanism as evidenced by stable mRNA transcript number, decreased DDAH1 protein concentration, decreased enzyme activity, elevated tissue asymmetric dimethylarginine, elevated asymmetric dimethylarginine/arginine ratio in plasma, and decreased whole blood nitrite concentration	755203	
3.5.3.18	medicine	in lung adenocarcinoma, isoform DDAH2 is expressed in fibroblasts of stroma of malignancies, with higher expression in minimally invasive adenocarcinoma and invasive adenocarcinoma than in adenocarcinoma in situ. Tumors with high stromal expression of DDAH2 have a poorer prognosis than those without	755643	
3.5.3.18	medicine	in patients with type 2 diabetes mellitus, the percentage of senescent endothelial progenitor cells increases while the expression of DDAH2 decreases concomitantly with an increase in the plasma levels of asymmetric dimethylarginine. Exogenous application of asymmetric dimethylarginine accelerates the senescence of cultured endothelial progenitor cells in a dose-dependent manner, and overexpression of DDAH2 inhibits high glucose-induced endothelial progenitor cells senescence. Resveratrol (activating silent information regulator SIRT1) inhibits high glucose-induced endothelial progenitor cells senescence by upregulating the expression of DDAH2 and decreasing the levels of asymmetric dimethylarginine	752652	
3.5.3.18	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	669780	
3.5.3.18	medicine	influence on atherosclerosis in experimental models by increased ADMA concentrations and reduced NO synthesis	697831	
3.5.3.18	medicine	novel therapeutic strategy for the treatment of chronic kidney disease	699943	
3.5.3.18	medicine	placental dysfunction of dimethylarginine dimethylaminohydrolase has been suggested as one of the initiating events in the development of preeclampsia	686991	
3.5.3.18	medicine	plasma asymmetric dimethylarginine/arginine ratios are elevated in children with acute severe malaria compared to 28-day follow-up values and compared to children with uncomplicated malaria or healthy children	755203	
3.5.3.18	medicine	protective effect of probucol on endothelium related to enhancement of DDAH activity	668175	
3.5.3.18	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	710771	
3.5.3.18	medicine	structure-based development of specific DDAH-1 inhibitors that might be useful in the therapeutic treatment of NOS dysfunction-related diseases	670913	
3.5.3.18	additional information	DDAH1 plays an important role in development	668120	
3.5.3.18	additional information	dimerization is not critical for the maintenance of the biological function of the protein	652942