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NG-Methylarginines: Biosynthesis, biochemical function and metabolism

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Summary

NG-Methylarginines (NG-monomethylarginine, NG, NG-dimethylarginine and NG, N′G-dimethylarginine) occur widely in nature in either proteinbound or in free states. They are posttranslationally synthesized by a group of enzymes called protein methylase I with S-adenosyl-L-methionine as the methyl donor. The enzymes are highly specific not only towards arginine residues but also towards the protein species. Since transmethylation reaction is energy-dependent in the form of S-adenosyl-L-methionine and is catalyzed a group of highly specific enzymes, it is quite logical to assume that the enzymatic methylation of protein-bound arginine residues play an important role in the regulation of the function and/or metabolism of the protein. When determined with histones asin vitro substrates, protein methylase I activity parallels closely the degree of cell proliferation, and the myelin basic protein (MBP)-specific protein methylase I activity decreases drastically in dysmyelinating mutant mouse brain during myelinating period, suggesting an important role played in the formation and/or maintenance of myelin. When the methylated proteins are degraded by intracellular proteolytic enzymes, free NG-methylarginines are generated. Some of these free NG-methylarginines, particularly NG-monomethylarginine, are extensively metabolized by decarboxylation, hydrolysis, transfer of methylamidine and deimination reaction. Recent experiment demonstrates that some of the NG-methylarginines may be involved in the neutralization of activity of nitric oxide (NO) which has attracted a great deal of attention as vascular smooth muscle relaxation factor.

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  1. Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 19140, Philadelphia, PA, USA

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Paik, W.K., Kim, S. NG-Methylarginines: Biosynthesis, biochemical function and metabolism. Amino Acids 4, 267–286 (1993). https://doi.org/10.1007/BF00805828

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