Biosynthesis of Methylguanidine in Isolated Rat Hepatocytes and in vivo

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Abstract
High doses of creatinine, which is known to stimulate the synthesis of methylguanidine, were administered to male Wistar rats i.p. to determine the organ in which methylguanidine is synthesized. Various tissues of the rats were frozen by a freeze clamp method before and 1, 2 and 3 h after injection, and methylguanidine was determined by high-pressure liquid chromatography using 9,10-phenanthrenequinone for fluorometric determination. The liver, kidney, lung, muscle, red blood cells and gut flora seemingly synthesize methylguanidine. The synthesis of methylguanidine in isolated hepatocytes prepared from normal rats following the addition of creatinine, arginine and guanidinoacetic acid to the incubation medium was measured. Synthesis of methylguanidine was observed only in those incubations which contained creatinine, and was dependent on the concentration of creatinine in the media and on the incubation period. Isolated rat hepatocytes also synthesized guanidine in the presence of guanidinoacetic acid. The liver is one of the organs which synthesize methylguanidine and also creatinine is the precursor.

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