Metabolic Pathway of Guanidino Compounds in Chronic Renal Failure
Guanidino compounds are considered to be one of the metabolic products of protein catabolism. Serum concentrations of some guanidino compounds especially methylguanidine (MG)1 and guanidinosuccinic acid (GSA)2 are increased in the uremic state. Recently, MG and GSA were found to have uremic toxicity in vitro3. Giovanetti4, et al., for example, brought out many uremic symptoms in normal dogs by repeatedly injecting MG until the MG concentration reached the uremic state. Cohen5 proposed the metabolic pathway of MG. He suggested that the metabolic origin of MG is mainly creatine and partially of arginine (Arg). The present authors have also suggested that there might be two metabolic origins of MG6. One is possibly Arg itself (or the metabolites of arginine); the other is creatinine (Cr). The present study aims to clarify the metabolic precursor of guanidino compounds, especially MG (Fig.l).
KeywordsUrinary Excretion Uremic Toxin Metabolic Origin Guanidino Compound Basal Nutrient Solution
Unable to display preview. Download preview PDF.
- S.Giovannetti, P.L.Balestri, and G.Barsotti, Methyl-guanidine in uremia, Arch. Iptern. Med., 131:709 (1973).Google Scholar
- 2.I.M.Stein, B.D.Cohen, and R.S.Kornhauser, Guanidinosuccinic acid in renal failure, experimental azotemia and inborn errors of the urea cycle, New Engl.J.Med., 280: 926 (1969).Google Scholar
- 3.S.Giovannetti, L.Cioni, P.L.Balestri, and M.Biagini, Evidence that guanidines and some related compounds cause hemolysis in chronic uremia, C1íz1.S., 34: 141 (1968).Google Scholar
- 4.S.Giovannetti, M.Biagini, P.L.Balestri, R.Navelesi, P.Giognoni, A.de Matteis, P.Ferro-Milone, and C.Perfetti, Uremia-like syndrome in dogs chronically intoxicated with methylguanidine and creatinine, Clin.Sci., 36: 445 (1969).Google Scholar
- 5.B.D.Cohen, Uremic toxins, Bull.N.Y.Acad.Med., 51:1228 (1975)Google Scholar
- 7.R.Platt, M.H.Roscoe, and F.W.Stuith, Experimental renal failure, Clin.Sci., 11: 217 (1952).Google Scholar
- 8.Y.Yamamoto, A.Saito, T.Manji, H.Nishi, K.Ito, K.Maeda, K.Ohta, and K.Kobayashi, A new automated analytical method for guanidino compounds and their cerebrospinal fluid levels in uremia, Trans.Am.Soc.Artif.Intern.Organs, 24: 61 (1976).Google Scholar
- 9.A.Ando, H.Mikami, T.Kikuchi, Y.Orita, and H.Abe, An automated analytical method for guanidino compounds; Determination of optimal deproteinization method, JEn.J. Clin.Chem., 9: 191 (1980).Google Scholar
- 10.J.B.Walker, End product repression in the creatine pathway of the developing chick embryo, in:“Advances in Enzyme Regulation”, Pergamon, New York (1963).Google Scholar
- 11.B.D.Cohen, Guanidinosuccinic acid in uremia, Arch.Intern. Med., 126: 846 (1970).Google Scholar