Asymmetric dimethylarginine

Figure 13.2 (a) Sequential methylation and demethylation of lysines catalyzed by histone methyl transferases (HMTs) and histone demethylases (HDMs), respectively, (b) Sequential methylation and demethylation of arginines catalyzed by HMTs and HDMs, respectively, leading to symmetric and asymmetric dimethylarginines. 

Homocysteine decreases the bioavailability of nitrous oxide (NO) via a mechanism involving glutathione peroxidase (37). Tawakol et al. (38) reported that hyperhomocysteinemia is associated with impaired endothelium-dependent vasodilation in humans. Homocysteine impairs the NO synthase pathway both in cell culture (39) and in monkeys with hyperhomocysteinemia, by increasing the levels of asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor (40). Elevation of ADMA may mediate endothelial dysfunction during experimental hyperhomocysteinemia in humans (41). However, Jonasson et al. (42) did not find increased ADMA levels in patients with coronary heart disease and hyperhomocysteinemia, nor did vitamin supplementation have any effect on ADMA levels in spite of substantial plasma tHcy reduction,... 

Stuhlinger MC, et al. Homocysteine impairs the nitric oxide synthase pathway role of asymmetric dimethylarginine, Circulation 2001 104(21 ) 2569-2575. 

Boger RH, et al. Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or hypercholesterolemia [In Process Citation], Arterioscler Thromb Vase Biol 2000 20(6) 1557-1564. 

Boger RH, et al, Elevation of asymmetrical dimethylarginine may mediate endothelial dysfunction during experimental hyperhomocyst(e)inaemia in humans. Clin Sci (Colch) 2001 ... 

Jonasson Tp et al. Hyperhomocysteinaemia is not associated with increased levels of asymmetric dimethylarginine in patients with ischaemic heart disease, Eur J Clin Invest 2003 33(7) 543-549. 

Maas R, Wenske S, Zabel M, et al. Elevation of asymmetrical dimethylarginine (ADMA) and coronary artery disease in men with erectile dysfunction. Eur Urol 2005 48 1004-1012. 

ElesberAA, Solomon H, Lennon RJ, etal. Coronary endothelial dysfunction is associated with erectile dysfunction and elevated asymmetric dimethylarginine in patients with early atherosclerosis. Eur HeartJ 2006 27 824-83 I. 

Let s start with this one because arginine is the raw material, the substrate, from which NO is made in the endothelium. To get the job done, you must have an adequate amount of eNOS, the enzyme that acts as a catalyst in the production process, and enough of the amino acid arginine. But the process can be blocked by high levels of asymmetric dimethylarginine (ADMA), a known inhibitor of NO synthesis. 

J. T. Kielstein, S. M. Bode-B5ger, J. C. Frolich, H. Haller and R. H. Boger, Relationship of Asymmetric Dimethylarginine to Dialysis Treatment and Atherosclerotic Disease. Kidney International 59(Suppl. 78) (2001) 9-13. 

R. J. Chan, R. H. BOger. S. M. Bode-B6ger, O. Tangphao. P. S. Tsao, T. F. Blaschke and J. P. Cooke, Asymmetric Dimethylarginine Increases Mononuclear Cell Adhesiveness in Hypercholesterolemic Humans, Arteriosclerosis. Thrombosis, and Va.scular Biology 20 ( 2000) 1040-1056. 

J. T. Kielstein, R. H. BSger, S. M. Bode-B6ger, J. Schaeffer, M. Barbey, K. M. Koch and J. C. Frdhlich, Asymmetric Dimethylarginine Plasma Concentrations Differ in Patients with End-Stage Renal Disease Relationship to Treatment Method and Atherosclerotic Disease, Journal of American Society of Nephrology 10 (1999) 594-600. 

Verhoeven, M.O., Teerlink, T., Kenemans, P., Vogelvang, T.E. and van der Mooren, M.J. (2007) Effects on asymmetric dimethylarginine of HMR 3339, a novel selective estrogen receptor modulator a 12-week, randomized, placebo-controlled, double-blind, doseranging study in healthy postmenopausal women. Menopause, 14, 235—242. 

DDAH itself may also have potential as a therapeutic protein in disease states marked by excess N dimethyl-L-arginine. For example, overexpression of DDAH has beneficial effects in transgenic mouse models of graft coronary artery disease and can enhance sensitivity to insulin. DDAH may also have beneficial effects in treating chronic kidney disease, as overexpressed DDAH appears to slow progression of renal dysfunction in rat models. " Elevated asymmetric dimethylarginine (ADMA) levels have also been identified in the development of chronic lung diseases, specifically pulmonary fibrosis. However, the causal relationship between ADMA and these conditions has yet to be explored in detail. ... 

T Plasma Concentration of Cellular Adhesion Molecules T Plasma Concentration of Asymmetric Dimethylarginine I Endothelial-Dependent Vasodilatation... 

McLaughlin T, Stuhlinger M, Lamendola C, et al. Plasma asymmetric dimethylarginine concentrations are elevated in obese insulin resistant women and fall with weight loss. J Clin Endocrinol Metab 2006 91 1896-2000. 

Fard, A., Tuck, C.H., Donis, J.A., Sciacca, R., Di Tulho, MR., Wu, H.D., Bryant, T.A., Chen, N.T., Torres-Tamayo, M., Ra-masamy, R., Berglund, L., Ginsberg, HN., Homma, S., and Cannon, PJ. (2000) Acute Elevations of Plasma Asymmetric Dimethylarginine and Impaired Endothelial Function in Response to a High-Fat Meal in Patients with Type 2 Diabetes, Arterioscler. Thromb. Vase. Biol. 20,2039-2044. 

Stefanadis, C., and Channon, K.M., 2009b. Association of plasma asymmetrical dimethylarginine (ADMA) with elevated vascular superoxide production and endothelial nitric oxide synthase uncoupling implications for endothelial function in human atherosclerosis. European Heart Journal. 30 1142 1150. 

Elevated asymmetric dimethylarginine concentrations are at increased risk for ischemic stroke in the elderly, and may account for increased risk of stroke in patients with hyper-Hcy. 

Yoo, J.H., and Lee, S.C., 2001. Elevated levels of plasma homocyst(e)ine and asymmetric dimethylarginine in elderly patients with stroke. Atherosclerosis. 158 425-430. 

Homocysteine metabolism is involved both in the synthesis and degradation of asymmetric dimethylarginine (ADMA), a potent endogenous NO-synthase inhibitor, which is thought to be an independent predictor of cardiovascular mortality in end-stage renal disease. 

Asymmetric dimethylarginine (ADMA), a potent endogenous nitric oxide (NO) synthase inhibitor. 

Asymmetric dimethylarginine (ADMA). Asymmetric dimethylarginine (ADMA) potently impairs the vascular endothelial function by inhibiting the production of nitric oxide (NO) through the antagonism with arginine, a substrate of NO. 

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