Homoarginine, arginine, and relatives: analysis, metabolism, transport, physiology, and pathology

The year 2008 witnessed the first report on the increase in the concentration of l-homoarginine (hArg) in the maternal plasma during human pregnancy. This observation, along with a well-known function of hArg, the methylene homologue of l-arginine (Arg), as a substrate for nitric oxide (NO) synthase, was the ignition for the start of intense research on the physiology and pathology of hArg. The circulating concentration of hArg was found to be lower in patients suffering from various diseases, and hArg emerged within only very few years as a novel cardiovascular risk factor. The compendium in hand comprises original and review articles covering several aspects of hArg, Arg and its symmetrically and asymmetrically guanidine (N (G))-dimethylated derivatives SDMA and ADMA, respectively. In contrast to ADMA and SDMA, low hArg concentrations in plasma or serum and in urine are associated with high risks for morbidity and mortality, notably in the renal and cardiovascular systems. Acutely and chronically administered Arg as a nutritional supplement or in the form of dietary proteins is safe in animals and humans and leads to concomitant formation of hArg and ADMA, albeit in a different hArg/ADMA ratio. Despite the close but opposite associations of hArg and ADMA with disease in adults, children and adolescents, the underlying biochemical processes are largely unknown, presumably not restricted to NO, and warrant deeper investigation. As the common substrate for hArg and ADMA, Arg may play a key role in the biosynthesis and homeostasis of hArg and ADMA, two putative antagonists. In animal models of stroke and obesity, hArg has beneficial effects. The potential utility of hArg as a therapeutic drug or nutritional supplement in humans and animals remains to be elaborated.