N(G)-Methylarginines: Biosynthesis, Biochemical Function and Metabolism

N(G)-Methylarginines (N(G)-monomethylarginine, N(G), N(G)-dimethylarginine and N(G), 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 N(G)-methylarginines are generated. Some of these free N(G)-methylarginines, particularly N(G)-monomethylarginine, are extensively metabolized by decarboxylation, hydrolysis, transfer of methylamidine and deimination reaction. Recent experiment demonstrates that some of the N(G)-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.