Biosynthesis of Guanidinosuccinic Acid in Isolated Rat Hepatocytes: Evaluation of Guanidine Cycle and Acidosis

Guanidinosuccinic acid (GSA), a guanidine derivative, is implicated as a uremic toxin1 To clarify the synthetic pathway of GSA and the mechanism of its increased synthesis in renal failure, we investigated GSA synthesis in isolated rat hepatocytes, in vitro and obtained the following results2. 1) GSA synthesis increased as urea concentration rose. 2) Ornithine and arginine3 which stimulated urea synthesis inhibited GSA synthesis. 3) D,LNorvaline which is an inhibitor4 of urea cycle enzymes: arginase, argininosuccinate synthetase and argininosuccinate lyase, inhibited GSA synthesis. These results support the theory that GSA is formed from urea via the guanidine cycle which consists of microsomal enzymes and urea cycle enzymes5. In this study, the guanidine cycle which is proposed as a synthetic pathway for GSA was examined in isolated rat hepatocytes. In addition, the effects of some basic conditions on GSA synthesis in isolated rat hepatocytes were investigated.