Asymmetrical dimethyl arginine

Wierzbicki AS, Solomon H, Lumb PJ, et al. Asymmetric dimethyl arginine levels correlate with cardiovascular risk factors in patients with erectile dysfunction. Atherosclerosis 2006 I 85 421-425. 

Fig. 9. Plasma asymmetric dimethyl arginine (ADMA), a compound detectable in human plasma and an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), increases after a fat meal in diabetic patients. It is associated with an increase in plasma triglycerides and impaired flow-mediated (FM) vasodilation [data from Fard etal. (92), reproduced with permission]. The increase in plasma ADMA in response to the high-fat meal was significantly and inversely related to a decrease in the percentage of vasodilation (r = -0.37, P= 0.007, n = 10).

Arginine methylation is catalysed by protein arginine methyltransferases (PRMTs, EC number 2.1.1.125), and thus far eight human PRMTs have been identified, with several more putative enzymes predicted. Two subclasses of PRMTs exist Class I PRMTs catalyse asymmetric dimethylation, while Class II PRMTs catalyse symmetric dimethylation of arginine. All three methyl-transferase subfamilies (SET-domain KMTs, DOTIL and PRMTs) utilise S-adenosylmethionine as an electrophilic methyl source. 

DDAH catalyzes the hydrolysis of A -methyl-L-arginine (12) and asymmetric A -dimethyl-L-argtnine (13) to yield L-citrulline (1) and the corresponding alkylamine (Figure 9)." " In vertebrates, two tissue-specific... 

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. ... 

Takahashi Y, Daitoku H, Hirota K, Tamiya HJ, Yokoyama A, Kako K, Nagashima Y, Nakamura A, Shimada T, Watanabe S, Yamagata K, Yasuda K, Ishii N, Fukamizu A. Asymmetric arginine dimethylation determines life span in C. elegans by regulating forkhead transcription factor DAF-16. Cell Metab. 2011 13 505-16. 

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