Abstract
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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
B. D. Cohen, Guanidinosuccinic acid in uremia, Arch. Intern. Med., 126: 846 (1970).
K. Aoyagi, S. Ohba, M. Narita and S. Tojo, Regulation of biosynthesis of guanidinosuccinic acid in isolated rat hepatocytes and in vivo, Kidney International, in press.
S. Kim, W. I. Paik and P. P. Cohen, Ammonia intoxication in rats: protection by N-carbamoyl-L-glutamate plus L-arginine, Proc. Nat. Acad. Sci. USA, 69: 3530 (1972).
T. Saeki, Y. Sato, S. Takada and T. Katsunuma, Regulation of urea synthesis in rat liver, J. Biochem., 86: 745 (1979).
S. Natelson and J. E. Sherwin, Proposed mechanism for urea nitrogen re-utilization: relationship between urea and proposed guanidine cycles, Clin. Chem., 25: 1343 (1979).
M. N. Berry and D. S. Friend, High-yield preparation of isolated liver cells, J. Cell. Biol., 43: 506 (1969).
R. N. Zahlten, W. S. Frederick and H. A. Lady, Regulation of glucose synthesis in hormone-sensitive isolated hepatocytes, Proc. Nat. Acad. Sci. USA, 70: 3213 (1973).
Y. Yamamoto, T. Manji, A. Saito, K. Maeda and K. Ohta, Ion-exchange chromatographic separation and fluorometric determination of guanidino compounds in physiological fluids, J. Chromatogra., 162: 327 (1979).
S. Natelson, H. Tseng and J. E. Sherwin, On the biosynthesis of guanidinosuccinate, Clin. Chem., 24: 2108 (1978).
S. Natelson, A. Koller, H. Tseng and R. F. Dods, Canaline carbamoyl-transferase in human liver as part of a metabolic cycle in which guanidino compounds are formed, Clin. Chem., 23: 960 (1977).
A. Koller, L. Aldwin and S. Natelson, Hepatic synthesis of canavaninosuccinate from ureidohomoserine and aspartate, and its conversion to guanidinosuccinate, Clin. Chem., 21: 1777 (1975).
K. Takahara, S. Nakanishi and S. Natelson, Studies on the reductive cleavage of canavanine and canavaninosuccinic acid, Arch. Biochem. Biophys., 145: 85 (1971).
H. Patel and B. Cohen, The guanidine cycle, Third international congress on nutrition and metabolism in renal diseases (France) 1982.
M. Stubbs and H. A. Krebs, The accumulation of aspartate in the presence of ethanol in rat liver, Biochemical J., 150: 41 (1975).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1985 Springer Science+Business Media New York
About this chapter
Cite this chapter
Aoyagi, K. et al. (1985). Biosynthesis of Guanidinosuccinic Acid in Isolated Rat Hepatocytes: Evaluation of Guanidine Cycle and Acidosis. In: Mori, A., Cohen, B.D., Lowenthal, A. (eds) Guanidines. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-0752-6_9
Download citation
DOI: https://doi.org/10.1007/978-1-4757-0752-6_9
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-0754-0
Online ISBN: 978-1-4757-0752-6
eBook Packages: Springer Book Archive