title: Biosynthesis of guanidine in isolated rat hepatocytes, perfused rat liver and intact animals.
abstract: Plasma levels of guanidine (G) are reported to be increased in uremic patients and are synthesized from various guanidino compounds via a chemical reaction involving the hydroxyl radical in vitro. To identify both the metabolic precursor and the synthesizing organ of G, we investigated the concentrations of G in various organs of rats administered several guanidino compounds and we attempted to synthesize G biologically using isolated rat hepatocytes or perfused rat liver. In addition, we investigated the effect of the peroxidative state on the G synthesis in isolated hepatocytes using various reagents which alter this condition. Results show that the concentration of G increased in the kidney, liver and muscle following the administration of L-canavanine. In addition, G increased in the kidney at 90 min after the administration of guanidinoacetic acid (GAA). Moreover, G is synthesized from L-canavanine in isolated rat hepatocytes and perfused rat liver, and G synthesis in hepatocytes is partially inhibited by the addition of superoxide dismutase, catalase, glutathione or ethylenediaminetetraacetic acid. These results suggest that L-canavanine is possibly a biological precursor and GAA is an endogenous precursor of G. Furthermore, it is suggested that these reactions are closely related to the peroxidative state.
authors.affiliation: Department of Internal Medicine, Kamitsuga General Hospital, Tochigi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takemura
authors.forename: S
authors.initials: S
authors.lastname: Nagase
authors.forename: K
authors.initials: K
authors.lastname: Aoyagi
authors.forename: M
authors.initials: M
authors.lastname: Gotoh
authors.forename: A
authors.initials: A
authors.lastname: Koyama
authors.forename: M
authors.initials: M
authors.lastname: Narita
mesh_terms: D000818:Animals; D002172:Canavanine / Q000494:pharmacology; D002478:Cells, Cultured; D016166:Free Radical Scavengers / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D019791:Guanidine; D006146:Guanidines / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009928:Organ Specificity / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016166:Free Radical Scavengers; D006146:Guanidines; D002172:Canavanine; C004946:glycocyamine; D019791:Guanidine; D005998:Glycine