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.

Creatine and Creatinine Metabolism

“…4) Some further Crn degradation pathways were proposed but have not been characterized in detail so far. Guanidinoacetate seems to be converted to guanidine in vivo (638,684,980). In normal rabbits, partial conversion of Crn to GBA was observed, whereas in a rabbit with decreased Crn clearance, GPA and Arg were suggested to be derived from Crn (83).…”

Renal handling of guanidino compounds in rat and rabbit.

“…We recently reported that ArgA could not be detected in the plasma of control rats (Levillain, Marescau & De Deyn, 1995) and given the fact that ArgA is present in IS and IM, a possible renal synthesis of this GC might be suggested. Recently, it has been reported that GAA might be a natural endogenous precursor of G synthesis in kidney, but not in brain, heart, lung, liver, spleen and muscle of the rat (Takemura, Nagase, Aoyogi, Gotoh, Koyama & Narita, 1994). Since G was found in the kidney of both species but mainly in the medulla, we suspected that the collecting duct might be involved in G synthesis or alternatively that G might be synthesized in another nephron structure, carried and stored in the collecting duct as reported for betaine (Miller, Schmid, Chen, Schmolke & Guder, 1996).…”