Asymmetric dimethylation

Figure 1.4 Example of histone cross-talk on histone H3. PRMT6 and the ASH2/WDR5/MLL complex are capable of methylation of H3R2 and H3K4, respectively (a). PRMT6 cannot methylate R2 in the presence of H3K4 trimethylation (b). Asymmetric dimethylation of R2 prevents...

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. 

Of the three fatty amines, the tertiary fatty amines, with three alkyl groups, find the most application in industries. They are further classified into three types (1) symmetrical trifatty amine (R3N), in which all three alkyl chains are identical (2) asymmetrical dimethyl fatty amine [RN(CH3)2] or methyl difatty amine (R2NCH3) and (3) those derived from primary or secondary amine by the reaction with ethylene oxide. These asymmetrical fatty amines are the bases for the manufacture of organomodified clay for the petroleum industry, biocides, and algicides. 

From benzophenone (560) and phenylsilane (559), mono- (561) and bis(diphenylmethyl)phenylsilane (562) can be obtained (equation 282)315. The asymmetric dimethyl(2,2-dimethyl-l-phenylprop-l-yloxy)phenylsilane (563) can be synthesized in the presence of a cationic rhodium complex (equation 283)316. An alkoxy replacement can be used for the synthesis of alkoxysilanes with non-identical alkoxy moieties, e.g. for diethoxymethoxysilane (565) (equation 284)317. 

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. 

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