Effects of agmatine, an active metabolite of arginine metabolism, on the kidney.

The amino acid L-arginine is a component of proteins and is involved in several metabolic pathways, including the urea cycle, the synthesis of creatine and the generation of nitric oxide [1]. In the last 2 years it has been established that arginine can also be decarboxylated, resulting in the formation of agmatine, 4(aminobutyl)guanidine. The enzyme arginine decarboxylase was thought to be present only in bacteria and lower eukaryotes such as plants and parasitic worms. Recently, however, an enzymatic.activity that decarboxylates arginine has been described in brain [2], kidney [3,4] and several other mammalian tissues [3,4]. This activity is associated with the mitochondrial fraction of cells [3,4]. Homology-based polymerase chain reaction amplification has uncovered an mRNA in a number of mammalian tissues, especially the kidney, that is highly homologous to the bacterial biosynthetic (speA) gene product but not the biodegradative (adi) gene product [3]. Agmatine has been identified in extracts of rat kidney as the o-phthalaldehyde derivative by high performance liquid chromatography [4,5] and as the hexafluoroacetylacetonate derivative by gas chromatographymass spectroscopy [Stickle D, Bohrer A, Berger R, Morrissey J, Klahr S, Turk J, unpublished]. The calculated concentration of agmatine in whole kidney extract is in the micromolar range. All of these studies strongly suggest that agmatine is produced within mammalian tissues and in particular the kidney.